Attila Szendroi - Academia.edu (original) (raw)
Papers by Attila Szendroi
The Canadian journal of urology, 2011
Prostate cancer is the second leading cause of cancer death among men in developed countries. Est... more Prostate cancer is the second leading cause of cancer death among men in developed countries. Estrogen receptor-alpha (ER-α), vitamin D receptor (VDR), and the calcium-sensing receptor (CaSR), partly through their effects on calcium levels are implicated in the proliferation and carcinogenesis in the prostate gland. VDR, ER-α and CaSR genes show polymorphisms in humans that appear to have clinical significance in many pathological conditions, such as prostate cancer. Our aim was to evaluate the role of ER-α (PvuII, XbaI), VDR (BsmI) and CaSR (A986S) gene polymorphisms and serum calcium levels in the pathogenesis of prostate cancer. Two hundred four patients with prostate cancer and 102 healthy controls were recruited into a hospital-based case control study. After genotyping, the relationship between the individual genotypes and prostate cancer was investigated. Both the ER-α XbaI and the VDR BsmI polymorphisms were significantly related to the risk of prostate cancer. An age adjust...
Oncology Reports, 2007
The accumulation of genetic alterations plays a role in the evolution of bladder cancer. These ch... more The accumulation of genetic alterations plays a role in the evolution of bladder cancer. These changes can be detected in the urine by DNA analysis of the cells exfoliated from the bladder wall enabling us to detect bladder cancer. The urine supernatant, besides the urine sediment, contains DNA, however in a much smaller amount. The origin of DNA in these two fractions is probably different. Our aim was to evaluate which fraction (supernatant or sediment) provides more reliable results in detecting tumors. We analyzed blood, urine and tumor samples taken from 80 individuals (44 patients with bladder cancer, 20 control patients and 16 healthy volunteers) by using 12 microsatellite markers mapped on 6 chromosomes. Microsatellite alterations were detected in the urine sediment and supernatant in 86% of the cancer cases. Urine sediment alone had a sensitivity of 68%, while urine supernatant alone indicated aberrations in 80% of the tumors. In the superficial (Ta/T1) cases, a considerabl...
Orvosi Hetilap, Sep 26, 2004
The authors have collected and processed data of 307 patients at Urological Department Semmelweis... more The authors have collected and processed data of 307 patients at Urological Department Semmelweis University, who were treated for renal tumour from June 1997 to December 2002. During this process on the basis of their work, they formed their opinion of the main steps of diagnostical, surgical and conservative therapeutical procedure with patients suffering from renal cell cancer. They established the fact that the data is parallel with retraceable international literature, therefore this work can be the starting-point of long term prospective studies. They call attention to the fact that 70% of the tumours were recognized without any symptoms, during examination indicated for other reasons, due to the widely spreading of ultrasound, computed tomography and other imaging techniques. The tumours are recognized and removed in earlier stages and it is to be hoped that it prolongs their life expectancy, and makes the quality of life of our patients much better.
Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences, 2014
Background: Complex indeterminate Bosniak category III renal cystic masses are traditionally cons... more Background: Complex indeterminate Bosniak category III renal cystic masses are traditionally considered to be malignant in 50%. Our aim was to retrospectively evaluate the attenuation characteristics in multiphase computed tomography (CT) and to determinate the incidence of malignancy based on histological findings on all Bosniak category III renal cystic masses investigated in our department between April 3, 2007 and November 21, 2013. Materials and Methods: Quadriphasic multidetector CT images of nineteen patients (mean age: 56.5 ± 16.5 years) with radiologically detected Bosniak category III lesions were reviewed retrospectively. All lesions were surgically removed, and the incidence of malignancy, based on pathological results was determined. Results: Calcification was present in four lesions (21%). The mean largest diameter was 48.7 ± 28.8 mm. All lesions were multilobulated and septated. Of the 19 removed lesions, 16 (84%) were malignant, and 3 (16%) were benign (one inflammat...
INTRODUCTION Signet-ring cell carcinoma of the urinary bladder can be primary - arising from the ... more INTRODUCTION Signet-ring cell carcinoma of the urinary bladder can be primary - arising from the bladder wall or urachus remnants - or metastatic from tumors originating in the stomach, colon, or breast. Saphir first described primary signet-ring cell cancer of the urinary bladder in 1955. Less than 100 cases have been reported in the literature since then. CASE REPORT We report a case of a 45-year-old woman who was admitted with gross hematuria. Cystoscopy revealed a necrotic tumor on the left bladder wall. A transurethral biopsy showed signet-ring cell carcinoma. The bladder tumor was diagnosed as the primary one. Radical cystectomy was performed with ureterosigmoidostomy (Mainz pouch II). Histological examination showed a primary signet-ring cell carcinoma of the bladder (pT3bN0M0). Following surgery, the patient received adjuvant chemotherapy with cisplatin and fluorouracil. CONCLUSIONS Primary signet-ring cell carcinoma of the urinary bladder is an extremely rare tumor, account...
A prosztatarak (PCA) a fejlett orszagokban a ferfiak masodik leggyakoribb daganatos halaloka. Az ... more A prosztatarak (PCA) a fejlett orszagokban a ferfiak masodik leggyakoribb daganatos halaloka. Az osztrogen, a D vitamin receptor (VDR) es a calcium sensing receptor reszben a kalcium szintre gyakorolt hatasukon keresztul befolyassal birnak a prosztata novekedesere es daganatos elfajulasara. Celunk az osztrogen (PvuII, XbaI), a D vitamin (BsmI) es a calcium sensing receptor (A986S) genek polimorfizmusanak valamint a szerum kalcium szintnek a prosztata daganat kialakulasara kifejtett hatasanak vizsgalata volt. Felmeresunkbe 204 prosztata daganatos beteget es 102 korban illesztett kontroll egyent vontunk be. A genotipusok meghatarozasa utan azok szerum kalcium szinttel valo kapcsolatat vizsgaltuk. Mind az osztrogen receptor alfa (ER-?) XbaI mind a VDR BsmI polimorfizmusa szignifikansan osszefuggott a prosztata daganat jelenletevel. Korban illesztett logisztikus regresszio soran a magasabb korrigalt szerum kalcium szint es a VDR Bb/bb genotipus egmastol fuggetlenul csokkentettek a prosz...
BACKGROUND EGFR and VEGFR2 protein expressions are hallmarks of clear cell renal cancer (RCC) wit... more BACKGROUND EGFR and VEGFR2 protein expressions are hallmarks of clear cell renal cancer (RCC) with questionable prognostic impact. The skeletal system is one of the most common metastatic sites of RCC. Unfortunately, there are no data for EGFR and VEGFR2 protein expression in such lesions. MATERIALS AND METHODS Twenty cases of bone metastatic clear cell RCC were analyzed. EGFR and VEGFR2 proteins were detected by immunohistochemistry and analyzed by morphometry scoring both % positivity and the intensity. RESULTS EGFR protein scores were significantly reduced in bone metastases of RCC due to the reduction of EGFR protein expression in about one third of the cases (7/20). The VEGFR2 protein-positive phenotype of clear cell RCC was relatively frequent (7/20, 35%), but was lost in bone metastases (2/20, 10%). CONCLUSION These data suggest a phenotypic/genotypic change of clear cell RCC during the progression to bones and warrant further investigation.
Journal of Clinical Oncology
e15523 Background: Bone metastasis is a frequent complication of ccRCC and predictors of this typ... more e15523 Background: Bone metastasis is a frequent complication of ccRCC and predictors of this type of progression are scanty. The aim of this study was to analyse HIF and HIF regulated gene expressions in bone metastatic ccRCC. Methods: A pre-target therapy era cohort of 125 ccRCC patients with <100 month follow-up period have been collected with paraffin embedded primary tumors. 65 patients developed bone metastasis where 45 metastases were available for analysis. RNA was isolated from FFPE tissues and gene expression of HIF1A, HIF2A as well as HIF-regulated genes GLUT1, LDH5, GAPDH, CAIX, VEGF, VEGFR2 and EPOR were measured by RT-PCR using B2M as control. Protein product of these genes was measured on TMA arrays using standardized immunohistochemistry and an image analysis program (Mirax Viewer, 3DHistech). Results: Expression of HIF1A and HIF2A was significantly increased in bone metastatic primary ccRCC tumor tissues both at mRNA and protein levels. Significant upregulation o...
European Urology Supplements
International journal of cancer, Jan 19, 2018
Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requi... more Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requiring systemic treatment. Although cytotoxic chemotherapy is of limited effectiveness, prospective clinical studies can hardly be conducted. Targeted therapeutic treatment approaches and potentially immunotherapy based on a biological rationale may provide an alternative strategy. We therefore subjected 70 urachal adenocarcinomas to targeted next-generation sequencing, conducted in situ and immunohistochemical analyses (including PD-L1 and DNA mismatch repair proteins [MMR]) and evaluated the microsatellite instability (MSI) status. The analytical findings were correlated with clinicopathological and outcome data and Kaplan-Meier and univariable/multivariable Cox regression analyses were performed. The patients had a mean age of 50 years, 66% were male and a 5-year overall survival (OS) of 58% and recurrence-free survival (RFS) of 45% was detected. Sequence variations were observed in TP5...
EFORT Open Reviews
Oncological management of skeletal metastases has changed dramatically in the last few decades. A... more Oncological management of skeletal metastases has changed dramatically in the last few decades. A significant number of patients survive for many years with their metastases. Surgeons are more active and the technical repertoire is broader, from plates to intramedullary devices to (tumour) endoprostheses. The philosophy of treatment should be different in the case of a trauma-related fracture and a pathological fracture. A proper algorithm for establishing a diagnosis and evaluation of prognostic factors helps in planning the surgical intervention. The aim of palliative surgery is usually to eliminate pain and to allow the patient to regain his/her mobility as well as to improve the quality of life through minimally invasive techniques using life-long durable devices. In a selected group of patients with an oncologically controlled primary tumour site and a solitary bone metastasis with positive prognostic factors, which meet the criteria for radical excision (approximately 10% to 1...
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](Orvosi hetilap, 2017
In Hungary and in the developed countries urinary stones occur more often due to nutritional habi... more In Hungary and in the developed countries urinary stones occur more often due to nutritional habits, obesity and sedentary lifestyle beside the endocrine and metabolic causes. In the daily urological and family doctor practice prevention should have an important role. Prevention is based not only on body weight control, physical exercise and medical treatment, but on proper diet as well. The nutritional components can change the consistence of urine, causing supersaturation, which is essential in stone formation. Specific nutritional components can either prevent stone formation (increased fluid intake, citrate, magnesium, fruits and vegetables) or either increase stone formation (decreased fluid intake, proteins, carbohydrates, oxalate, salt, increased calcium intake, ascorbic-acid etc). We summarized evidence-based practical dietary suggestions on the primary and secondary prevention of urinary stones. Orv Hetil. 2017; 158(22): 851-855.
Oncotarget, 2014
Purpose: Targeted therapy represents an attractive alternative for rare tumors such as urachal ca... more Purpose: Targeted therapy represents an attractive alternative for rare tumors such as urachal carcinoma (UrC). The aim of this study was to assess the mutations of the most commonly affected 5 genes in the targetable EGFR-pathway in UrC and comapre their frequencies to those of found in urothelial and colorectal cancer. Materials and Methods: Mutational hot-spots of selected genes were tested in 22 UrC samples by pyrosequencing. Mutational patterns were compared to those published for colorectal and urothelial cancers. Furthermore, we sought correlations between mutations and clinicopathological and follow-up data. Results: We found 11 mutations in 10 of 22 (45%) patients. The most frequently mutated gene was KRAS (27%) followed by BRAF (18%) and NRAS (5%), while no mutations were detected in the EGFR and PIK3CA genes. No correlation was found between the mutation status and clinicopathological parameters (Sheldon/Mayo stage, tumor grade, metastases). Furthermore, none of the mutations correlated with progression-free or overall survival. Conclusions: The mutation pattern of UrC is more similar to colorectal than to urothelial cancer. However, the mutation characteristics of UrC seems to be unique suggesting that clinical decision-making for UrC cannot be simply adopted from urothelial or colorectal carcinoma. The high occurence of EGFR-pathway mutations warrants the testing for KRAS and BRAF mutations when considering anti-EGFR therapy in UrC.
Oncotarget, 2014
BACKGROUND: Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly... more BACKGROUND: Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly established. We tested prognostic value of HIF1a/HIF2a and their selected target genes in primary tumors and corresponding bone metastases. RESULTS: Expression of HIF2a was lower in mRCC both at mRNA and protein levels (p/mRNA/=0.011, p/protein/=0.001) while HIF1a was similar to nmRCC. At the protein level, CAIX, GAPDH and GLUT1 were increased in mRCC. In all primary RCCs, low HIF2a and high HIF1a as well as CAIX, GAPDH and GLUT1 expressions correlated with adverse prognosis, while VEGFR2 and EPOR gene expressions were associated with favorable prognosis. Multivariate analysis confirmed high HIF2α protein expression as an independent risk factor. Prognostic validation of HIFs, LDH, EPOR and VEGFR2 in RNA-Seq data confirmed higher HIF1a gene expression in primary RCC as an adverse (p=0.07), whereas higher HIF2a and VEGFR2 expressions as favorable prognostic factors. HIF1a/HIF2a-index (HIF-index) proved to be an independent prognostic factor in both the discovery and the TCGA cohort. PATIENTS AND METHODS: Expressions of HIF1a and HIF2a as well as their 7 target genes were analysed on the mRNA and protein level in 59 non-metastatic ccRCCs (nmRCC), 40 bone metastatic primary ccRCCs (mRCC) and 55 corresponding bone metastases. Results were validated in 399 ccRCCs from the TCGA project. CONCLUSIONS: We identified HIF2a protein as an independent marker of the metastatic potential of ccRCC, however, unlike HIF1a, increased HIF2a expression is a favorable prognostic factor. The HIF-index incorporated these two markers into a strong prognostic biomarker of ccRCC.
European Urology Supplements, 2015
The Journal of Urology, 2015
Urachal carcinoma of the bladder is a rare malignancy. Its histological phenotype is similar to t... more Urachal carcinoma of the bladder is a rare malignancy. Its histological phenotype is similar to that of primary bladder and colorectal adenocarcinoma. The aim of this study was to explore the expression and prognostic relevance of 6 select protein markers of urachal carcinoma of the bladder, including p53, Ki67, RHAMM, BGN, IMP3 and MMP-7, which were formerly shown to be prognostic in urothelial carcinoma and colorectal adenocarcinoma. Clinical and followup data were obtained on a total of 26 patients with urachal carcinoma of the bladder treated at 2 university hospitals. Immunohistochemical analysis of p53, Ki67, RHAMM, BGN, IMP3 and MMP-7 expression was performed in samples from 15 patients. Clinicopathological parameters and immunohistochemical results were tested for prognostic value on univariable and multivariable analyses. Followup was 50 months. Five-year overall and progression-free survival was 46% and 32%, respectively. On multivariable analysis a positive resection margin was an independent predictor of poor overall survival (p = 0.025). RHAMM (p = 0.0431), IMP3 (p = 0.0052), Ki67 (p = 0.0006) and p53 (p = 0.0024) expression rates were significantly increased in urachal carcinoma of the bladder cells compared to normal urothelium. IMP3 was elevated in Sheldon tumor stage IIIA compared to IIIB or greater (p = 0.0048). None of the analyzed protein markers was associated with survival. The independent prognostic value of a positive resection margin underlines the importance of complete surgical removal of urachal carcinoma of the bladder combined with en bloc resection of the median umbilical ligament and umbilicus. Our results in a limited number of samples show that Ki67, p53, RHAMM and IMP3 expression is enhanced but has no prognostic significance in urachal carcinoma of the bladder.
The Canadian journal of urology, 2010
A renal cell cancer patient with late onset of multiorgan metastases showed an unusually long sur... more A renal cell cancer patient with late onset of multiorgan metastases showed an unusually long survival following surgical resection. Femoral metastasis appeared 11 years, and contra lateral kidney and adrenal gland metastasis 19 years after the primary nephrectomy, respectively. Following the resection of the femur and implantation of endoprosthesis and removal of adrenal gland and partial nephrectomy, the patient was disease-free 20 years after the first diagnosis of cancer. The long survival and successful treatment underline the importance and efficiency of radical metastasectomy even in the case of late onset multiorgan metastases of renal cell cancer. The life expectancies are better in the late onset of bone metastasis following the nephrectomy. The very late onset of metastases in this case shows however the importance of lifelong follow up.
The Canadian journal of urology, 2008
Signet-ring cell carcinoma of the urinary bladder can be primary - arising from the bladder wall ... more Signet-ring cell carcinoma of the urinary bladder can be primary - arising from the bladder wall or urachus remnants - or metastatic from tumors originating in the stomach, colon, or breast. Saphir first described primary signet-ring cell cancer of the urinary bladder in 1955. Less than 100 cases have been reported in the literature since then. We report a case of a 45-year-old woman who was admitted with gross hematuria. Cystoscopy revealed a necrotic tumor on the left bladder wall. A transurethral biopsy showed signet-ring cell carcinoma. The bladder tumor was diagnosed as the primary one. Radical cystectomy was performed with ureterosigmoidostomy (Mainz pouch II). Histological examination showed a primary signet-ring cell carcinoma of the bladder (pT3bN0M0). Following surgery, the patient received adjuvant chemotherapy with cisplatin and fluorouracil. Primary signet-ring cell carcinoma of the urinary bladder is an extremely rare tumor, accounting for approximately 0.24% of all bl...
Anticancer research
EGFR and VEGFR2 protein expressions are hallmarks of clear cell renal cancer (RCC) with questiona... more EGFR and VEGFR2 protein expressions are hallmarks of clear cell renal cancer (RCC) with questionable prognostic impact. The skeletal system is one of the most common metastatic sites of RCC. Unfortunately, there are no data for EGFR and VEGFR2 protein expression in such lesions. Twenty cases of bone metastatic clear cell RCC were analyzed. EGFR and VEGFR2 proteins were detected by immunohistochemistry and analyzed by morphometry scoring both % positivity and the intensity. EGFR protein scores were significantly reduced in bone metastases of RCC due to the reduction of EGFR protein expression in about one third of the cases (7/20). The VEGFR2 protein-positive phenotype of clear cell RCC was relatively frequent (7/20, 35%), but was lost in bone metastases (2/20, 10%). These data suggest a phenotypic/genotypic change of clear cell RCC during the progression to bones and warrant further investigation.
The Canadian journal of urology, 2011
Prostate cancer is the second leading cause of cancer death among men in developed countries. Est... more Prostate cancer is the second leading cause of cancer death among men in developed countries. Estrogen receptor-alpha (ER-α), vitamin D receptor (VDR), and the calcium-sensing receptor (CaSR), partly through their effects on calcium levels are implicated in the proliferation and carcinogenesis in the prostate gland. VDR, ER-α and CaSR genes show polymorphisms in humans that appear to have clinical significance in many pathological conditions, such as prostate cancer. Our aim was to evaluate the role of ER-α (PvuII, XbaI), VDR (BsmI) and CaSR (A986S) gene polymorphisms and serum calcium levels in the pathogenesis of prostate cancer. Two hundred four patients with prostate cancer and 102 healthy controls were recruited into a hospital-based case control study. After genotyping, the relationship between the individual genotypes and prostate cancer was investigated. Both the ER-α XbaI and the VDR BsmI polymorphisms were significantly related to the risk of prostate cancer. An age adjust...
Oncology Reports, 2007
The accumulation of genetic alterations plays a role in the evolution of bladder cancer. These ch... more The accumulation of genetic alterations plays a role in the evolution of bladder cancer. These changes can be detected in the urine by DNA analysis of the cells exfoliated from the bladder wall enabling us to detect bladder cancer. The urine supernatant, besides the urine sediment, contains DNA, however in a much smaller amount. The origin of DNA in these two fractions is probably different. Our aim was to evaluate which fraction (supernatant or sediment) provides more reliable results in detecting tumors. We analyzed blood, urine and tumor samples taken from 80 individuals (44 patients with bladder cancer, 20 control patients and 16 healthy volunteers) by using 12 microsatellite markers mapped on 6 chromosomes. Microsatellite alterations were detected in the urine sediment and supernatant in 86% of the cancer cases. Urine sediment alone had a sensitivity of 68%, while urine supernatant alone indicated aberrations in 80% of the tumors. In the superficial (Ta/T1) cases, a considerabl...
Orvosi Hetilap, Sep 26, 2004
The authors have collected and processed data of 307 patients at Urological Department Semmelweis... more The authors have collected and processed data of 307 patients at Urological Department Semmelweis University, who were treated for renal tumour from June 1997 to December 2002. During this process on the basis of their work, they formed their opinion of the main steps of diagnostical, surgical and conservative therapeutical procedure with patients suffering from renal cell cancer. They established the fact that the data is parallel with retraceable international literature, therefore this work can be the starting-point of long term prospective studies. They call attention to the fact that 70% of the tumours were recognized without any symptoms, during examination indicated for other reasons, due to the widely spreading of ultrasound, computed tomography and other imaging techniques. The tumours are recognized and removed in earlier stages and it is to be hoped that it prolongs their life expectancy, and makes the quality of life of our patients much better.
Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences, 2014
Background: Complex indeterminate Bosniak category III renal cystic masses are traditionally cons... more Background: Complex indeterminate Bosniak category III renal cystic masses are traditionally considered to be malignant in 50%. Our aim was to retrospectively evaluate the attenuation characteristics in multiphase computed tomography (CT) and to determinate the incidence of malignancy based on histological findings on all Bosniak category III renal cystic masses investigated in our department between April 3, 2007 and November 21, 2013. Materials and Methods: Quadriphasic multidetector CT images of nineteen patients (mean age: 56.5 ± 16.5 years) with radiologically detected Bosniak category III lesions were reviewed retrospectively. All lesions were surgically removed, and the incidence of malignancy, based on pathological results was determined. Results: Calcification was present in four lesions (21%). The mean largest diameter was 48.7 ± 28.8 mm. All lesions were multilobulated and septated. Of the 19 removed lesions, 16 (84%) were malignant, and 3 (16%) were benign (one inflammat...
INTRODUCTION Signet-ring cell carcinoma of the urinary bladder can be primary - arising from the ... more INTRODUCTION Signet-ring cell carcinoma of the urinary bladder can be primary - arising from the bladder wall or urachus remnants - or metastatic from tumors originating in the stomach, colon, or breast. Saphir first described primary signet-ring cell cancer of the urinary bladder in 1955. Less than 100 cases have been reported in the literature since then. CASE REPORT We report a case of a 45-year-old woman who was admitted with gross hematuria. Cystoscopy revealed a necrotic tumor on the left bladder wall. A transurethral biopsy showed signet-ring cell carcinoma. The bladder tumor was diagnosed as the primary one. Radical cystectomy was performed with ureterosigmoidostomy (Mainz pouch II). Histological examination showed a primary signet-ring cell carcinoma of the bladder (pT3bN0M0). Following surgery, the patient received adjuvant chemotherapy with cisplatin and fluorouracil. CONCLUSIONS Primary signet-ring cell carcinoma of the urinary bladder is an extremely rare tumor, account...
A prosztatarak (PCA) a fejlett orszagokban a ferfiak masodik leggyakoribb daganatos halaloka. Az ... more A prosztatarak (PCA) a fejlett orszagokban a ferfiak masodik leggyakoribb daganatos halaloka. Az osztrogen, a D vitamin receptor (VDR) es a calcium sensing receptor reszben a kalcium szintre gyakorolt hatasukon keresztul befolyassal birnak a prosztata novekedesere es daganatos elfajulasara. Celunk az osztrogen (PvuII, XbaI), a D vitamin (BsmI) es a calcium sensing receptor (A986S) genek polimorfizmusanak valamint a szerum kalcium szintnek a prosztata daganat kialakulasara kifejtett hatasanak vizsgalata volt. Felmeresunkbe 204 prosztata daganatos beteget es 102 korban illesztett kontroll egyent vontunk be. A genotipusok meghatarozasa utan azok szerum kalcium szinttel valo kapcsolatat vizsgaltuk. Mind az osztrogen receptor alfa (ER-?) XbaI mind a VDR BsmI polimorfizmusa szignifikansan osszefuggott a prosztata daganat jelenletevel. Korban illesztett logisztikus regresszio soran a magasabb korrigalt szerum kalcium szint es a VDR Bb/bb genotipus egmastol fuggetlenul csokkentettek a prosz...
BACKGROUND EGFR and VEGFR2 protein expressions are hallmarks of clear cell renal cancer (RCC) wit... more BACKGROUND EGFR and VEGFR2 protein expressions are hallmarks of clear cell renal cancer (RCC) with questionable prognostic impact. The skeletal system is one of the most common metastatic sites of RCC. Unfortunately, there are no data for EGFR and VEGFR2 protein expression in such lesions. MATERIALS AND METHODS Twenty cases of bone metastatic clear cell RCC were analyzed. EGFR and VEGFR2 proteins were detected by immunohistochemistry and analyzed by morphometry scoring both % positivity and the intensity. RESULTS EGFR protein scores were significantly reduced in bone metastases of RCC due to the reduction of EGFR protein expression in about one third of the cases (7/20). The VEGFR2 protein-positive phenotype of clear cell RCC was relatively frequent (7/20, 35%), but was lost in bone metastases (2/20, 10%). CONCLUSION These data suggest a phenotypic/genotypic change of clear cell RCC during the progression to bones and warrant further investigation.
Journal of Clinical Oncology
e15523 Background: Bone metastasis is a frequent complication of ccRCC and predictors of this typ... more e15523 Background: Bone metastasis is a frequent complication of ccRCC and predictors of this type of progression are scanty. The aim of this study was to analyse HIF and HIF regulated gene expressions in bone metastatic ccRCC. Methods: A pre-target therapy era cohort of 125 ccRCC patients with <100 month follow-up period have been collected with paraffin embedded primary tumors. 65 patients developed bone metastasis where 45 metastases were available for analysis. RNA was isolated from FFPE tissues and gene expression of HIF1A, HIF2A as well as HIF-regulated genes GLUT1, LDH5, GAPDH, CAIX, VEGF, VEGFR2 and EPOR were measured by RT-PCR using B2M as control. Protein product of these genes was measured on TMA arrays using standardized immunohistochemistry and an image analysis program (Mirax Viewer, 3DHistech). Results: Expression of HIF1A and HIF2A was significantly increased in bone metastatic primary ccRCC tumor tissues both at mRNA and protein levels. Significant upregulation o...
European Urology Supplements
International journal of cancer, Jan 19, 2018
Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requi... more Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requiring systemic treatment. Although cytotoxic chemotherapy is of limited effectiveness, prospective clinical studies can hardly be conducted. Targeted therapeutic treatment approaches and potentially immunotherapy based on a biological rationale may provide an alternative strategy. We therefore subjected 70 urachal adenocarcinomas to targeted next-generation sequencing, conducted in situ and immunohistochemical analyses (including PD-L1 and DNA mismatch repair proteins [MMR]) and evaluated the microsatellite instability (MSI) status. The analytical findings were correlated with clinicopathological and outcome data and Kaplan-Meier and univariable/multivariable Cox regression analyses were performed. The patients had a mean age of 50 years, 66% were male and a 5-year overall survival (OS) of 58% and recurrence-free survival (RFS) of 45% was detected. Sequence variations were observed in TP5...
EFORT Open Reviews
Oncological management of skeletal metastases has changed dramatically in the last few decades. A... more Oncological management of skeletal metastases has changed dramatically in the last few decades. A significant number of patients survive for many years with their metastases. Surgeons are more active and the technical repertoire is broader, from plates to intramedullary devices to (tumour) endoprostheses. The philosophy of treatment should be different in the case of a trauma-related fracture and a pathological fracture. A proper algorithm for establishing a diagnosis and evaluation of prognostic factors helps in planning the surgical intervention. The aim of palliative surgery is usually to eliminate pain and to allow the patient to regain his/her mobility as well as to improve the quality of life through minimally invasive techniques using life-long durable devices. In a selected group of patients with an oncologically controlled primary tumour site and a solitary bone metastasis with positive prognostic factors, which meet the criteria for radical excision (approximately 10% to 1...
Orvosi hetilap, 2017
In Hungary and in the developed countries urinary stones occur more often due to nutritional habi... more In Hungary and in the developed countries urinary stones occur more often due to nutritional habits, obesity and sedentary lifestyle beside the endocrine and metabolic causes. In the daily urological and family doctor practice prevention should have an important role. Prevention is based not only on body weight control, physical exercise and medical treatment, but on proper diet as well. The nutritional components can change the consistence of urine, causing supersaturation, which is essential in stone formation. Specific nutritional components can either prevent stone formation (increased fluid intake, citrate, magnesium, fruits and vegetables) or either increase stone formation (decreased fluid intake, proteins, carbohydrates, oxalate, salt, increased calcium intake, ascorbic-acid etc). We summarized evidence-based practical dietary suggestions on the primary and secondary prevention of urinary stones. Orv Hetil. 2017; 158(22): 851-855.
Oncotarget, 2014
Purpose: Targeted therapy represents an attractive alternative for rare tumors such as urachal ca... more Purpose: Targeted therapy represents an attractive alternative for rare tumors such as urachal carcinoma (UrC). The aim of this study was to assess the mutations of the most commonly affected 5 genes in the targetable EGFR-pathway in UrC and comapre their frequencies to those of found in urothelial and colorectal cancer. Materials and Methods: Mutational hot-spots of selected genes were tested in 22 UrC samples by pyrosequencing. Mutational patterns were compared to those published for colorectal and urothelial cancers. Furthermore, we sought correlations between mutations and clinicopathological and follow-up data. Results: We found 11 mutations in 10 of 22 (45%) patients. The most frequently mutated gene was KRAS (27%) followed by BRAF (18%) and NRAS (5%), while no mutations were detected in the EGFR and PIK3CA genes. No correlation was found between the mutation status and clinicopathological parameters (Sheldon/Mayo stage, tumor grade, metastases). Furthermore, none of the mutations correlated with progression-free or overall survival. Conclusions: The mutation pattern of UrC is more similar to colorectal than to urothelial cancer. However, the mutation characteristics of UrC seems to be unique suggesting that clinical decision-making for UrC cannot be simply adopted from urothelial or colorectal carcinoma. The high occurence of EGFR-pathway mutations warrants the testing for KRAS and BRAF mutations when considering anti-EGFR therapy in UrC.
Oncotarget, 2014
BACKGROUND: Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly... more BACKGROUND: Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly established. We tested prognostic value of HIF1a/HIF2a and their selected target genes in primary tumors and corresponding bone metastases. RESULTS: Expression of HIF2a was lower in mRCC both at mRNA and protein levels (p/mRNA/=0.011, p/protein/=0.001) while HIF1a was similar to nmRCC. At the protein level, CAIX, GAPDH and GLUT1 were increased in mRCC. In all primary RCCs, low HIF2a and high HIF1a as well as CAIX, GAPDH and GLUT1 expressions correlated with adverse prognosis, while VEGFR2 and EPOR gene expressions were associated with favorable prognosis. Multivariate analysis confirmed high HIF2α protein expression as an independent risk factor. Prognostic validation of HIFs, LDH, EPOR and VEGFR2 in RNA-Seq data confirmed higher HIF1a gene expression in primary RCC as an adverse (p=0.07), whereas higher HIF2a and VEGFR2 expressions as favorable prognostic factors. HIF1a/HIF2a-index (HIF-index) proved to be an independent prognostic factor in both the discovery and the TCGA cohort. PATIENTS AND METHODS: Expressions of HIF1a and HIF2a as well as their 7 target genes were analysed on the mRNA and protein level in 59 non-metastatic ccRCCs (nmRCC), 40 bone metastatic primary ccRCCs (mRCC) and 55 corresponding bone metastases. Results were validated in 399 ccRCCs from the TCGA project. CONCLUSIONS: We identified HIF2a protein as an independent marker of the metastatic potential of ccRCC, however, unlike HIF1a, increased HIF2a expression is a favorable prognostic factor. The HIF-index incorporated these two markers into a strong prognostic biomarker of ccRCC.
European Urology Supplements, 2015
The Journal of Urology, 2015
Urachal carcinoma of the bladder is a rare malignancy. Its histological phenotype is similar to t... more Urachal carcinoma of the bladder is a rare malignancy. Its histological phenotype is similar to that of primary bladder and colorectal adenocarcinoma. The aim of this study was to explore the expression and prognostic relevance of 6 select protein markers of urachal carcinoma of the bladder, including p53, Ki67, RHAMM, BGN, IMP3 and MMP-7, which were formerly shown to be prognostic in urothelial carcinoma and colorectal adenocarcinoma. Clinical and followup data were obtained on a total of 26 patients with urachal carcinoma of the bladder treated at 2 university hospitals. Immunohistochemical analysis of p53, Ki67, RHAMM, BGN, IMP3 and MMP-7 expression was performed in samples from 15 patients. Clinicopathological parameters and immunohistochemical results were tested for prognostic value on univariable and multivariable analyses. Followup was 50 months. Five-year overall and progression-free survival was 46% and 32%, respectively. On multivariable analysis a positive resection margin was an independent predictor of poor overall survival (p = 0.025). RHAMM (p = 0.0431), IMP3 (p = 0.0052), Ki67 (p = 0.0006) and p53 (p = 0.0024) expression rates were significantly increased in urachal carcinoma of the bladder cells compared to normal urothelium. IMP3 was elevated in Sheldon tumor stage IIIA compared to IIIB or greater (p = 0.0048). None of the analyzed protein markers was associated with survival. The independent prognostic value of a positive resection margin underlines the importance of complete surgical removal of urachal carcinoma of the bladder combined with en bloc resection of the median umbilical ligament and umbilicus. Our results in a limited number of samples show that Ki67, p53, RHAMM and IMP3 expression is enhanced but has no prognostic significance in urachal carcinoma of the bladder.
The Canadian journal of urology, 2010
A renal cell cancer patient with late onset of multiorgan metastases showed an unusually long sur... more A renal cell cancer patient with late onset of multiorgan metastases showed an unusually long survival following surgical resection. Femoral metastasis appeared 11 years, and contra lateral kidney and adrenal gland metastasis 19 years after the primary nephrectomy, respectively. Following the resection of the femur and implantation of endoprosthesis and removal of adrenal gland and partial nephrectomy, the patient was disease-free 20 years after the first diagnosis of cancer. The long survival and successful treatment underline the importance and efficiency of radical metastasectomy even in the case of late onset multiorgan metastases of renal cell cancer. The life expectancies are better in the late onset of bone metastasis following the nephrectomy. The very late onset of metastases in this case shows however the importance of lifelong follow up.
The Canadian journal of urology, 2008
Signet-ring cell carcinoma of the urinary bladder can be primary - arising from the bladder wall ... more Signet-ring cell carcinoma of the urinary bladder can be primary - arising from the bladder wall or urachus remnants - or metastatic from tumors originating in the stomach, colon, or breast. Saphir first described primary signet-ring cell cancer of the urinary bladder in 1955. Less than 100 cases have been reported in the literature since then. We report a case of a 45-year-old woman who was admitted with gross hematuria. Cystoscopy revealed a necrotic tumor on the left bladder wall. A transurethral biopsy showed signet-ring cell carcinoma. The bladder tumor was diagnosed as the primary one. Radical cystectomy was performed with ureterosigmoidostomy (Mainz pouch II). Histological examination showed a primary signet-ring cell carcinoma of the bladder (pT3bN0M0). Following surgery, the patient received adjuvant chemotherapy with cisplatin and fluorouracil. Primary signet-ring cell carcinoma of the urinary bladder is an extremely rare tumor, accounting for approximately 0.24% of all bl...
Anticancer research
EGFR and VEGFR2 protein expressions are hallmarks of clear cell renal cancer (RCC) with questiona... more EGFR and VEGFR2 protein expressions are hallmarks of clear cell renal cancer (RCC) with questionable prognostic impact. The skeletal system is one of the most common metastatic sites of RCC. Unfortunately, there are no data for EGFR and VEGFR2 protein expression in such lesions. Twenty cases of bone metastatic clear cell RCC were analyzed. EGFR and VEGFR2 proteins were detected by immunohistochemistry and analyzed by morphometry scoring both % positivity and the intensity. EGFR protein scores were significantly reduced in bone metastases of RCC due to the reduction of EGFR protein expression in about one third of the cases (7/20). The VEGFR2 protein-positive phenotype of clear cell RCC was relatively frequent (7/20, 35%), but was lost in bone metastases (2/20, 10%). These data suggest a phenotypic/genotypic change of clear cell RCC during the progression to bones and warrant further investigation.