Dimitri Korol - Academia.edu (original) (raw)

Papers by Dimitri Korol

Modern Pathology, 2009

The biological behavior of chronic lymphocytic leukemia and small lymphocytic lymphoma is unpredi... more The biological behavior of chronic lymphocytic leukemia and small lymphocytic lymphoma is unpredictable. Nonetheless, non-mutated IgV H gene rearrangement, ATM (11q22-23) and p53 (17p13) deletion are recognized as unfavorable prognosticators in chronic lymphocytic leukemia. The mRNA expression of activation-induced cytidine deaminase (AID), an enzyme indispensable for somatic hypermutation processes, was claimed to be predictive of non-mutated chronic lymphocytic leukemia cells in blood. Here, we evaluated AID protein expression compared with known molecular and immunohistochemical prognostic indicators in 71 chronic lymphocytic leukemia/small lymphocytic lymphoma patients using a tissue microarray approach. We found AID heterogeneously expressed in tumor cells as shown by colocalization analysis for CD5 and CD23. Ki-67 positive paraimmunoblasts of the proliferation centers displayed the highest expression. This observation is reflected by a significant association of AID positivity with a high proliferation rate (P ¼ 0.012). ATM deletion was detected in 10% (6/63) of patients and p53 deletion in 19% (13/67) of patients. Moreover, both ATM (P ¼ 0.002) and p53 deletion (P ¼ 0.004) were significantly associated with AID. IgV H gene mutation was seen in 45% (27/60) of patients. Twenty-five percent (17/69) of patients with AID-positive chronic lymphocytic leukemia/small lymphocytic lymphoma displayed a shorter survival than AID-negative chronic lymphocytic leukemia/small lymphocytic lymphoma patients (61 vs 130 months, P ¼ 0.001). Although there was a trend, we could not show an association with the IgV H gene mutation status. Taken together, our study shows that AID expression is an indicator of an unfavorable prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma patients, although it is not a surrogate marker for the IgV H status. Furthermore, the microenvironment of proliferation centers seems to influence AID regulation and might be an initiating factor in its transformation.

Annals of Oncology, 2018

Background: The vascular endothelial growth factor antibody bevacizumab (Avastin V R), received a... more Background: The vascular endothelial growth factor antibody bevacizumab (Avastin V R), received approval for the treatment of recurrent glioblastoma in many countries including the USA and Switzerland, but not the European Union, in 2009. Here, we explored the hypothesis that the approval of bevacizumab improved outcome with glioblastoma on a population level. Patients and methods: The prognostic significance of epidemiological, molecular genetic, and clinical data including treatment for glioblastoma patients diagnosed from 2010 to 2014 in the Canton of Zurich, Switzerland, was retrospectively analyzed using log-rank test and Cox proportional hazards models. Data were compared with data for the years 2005-2009. Results: In total, 310 glioblastoma patients were identified in the years 2010-2014. Median overall survival was 13.5 months for patients with known isocitrate dehydrogenase (IDH) wild-type (wt) (IDH1 R132H-non-mutant) tumors (N ¼ 248), compared with 11.3 months for IDH wt patients (P ¼ 0.761) before (2005-2009). In the IDH wt cohort, bevacizumab use at any time increased from 19% in 2005-2009 to 49% in 2010-2014. Multivariate analysis did not identify bevacizumab exposure at any time to be associated with survival. Yet, upon the second-line treatment, baseline doses of corticosteroids were reduced by more than half in 83% of patients on bevacizumab compared with 48% of the patients treated with bevacizumab-free regimens (P ¼ 0.007). Conclusion: This epidemiological study of a small, but clinically well-annotated patient cohort fails to support the assumption that the strong increase of bevacizumab use since 2010 improved survival in glioblastoma although clinical benefit associated with decreased steroid use may have been achieved.

European Journal of Cancer, 2014

Journal of Cytology & Histology, 2014

Knowledge about the biology and prognostic markers of neuroendocrine tumours (NET) of the lungs i... more Knowledge about the biology and prognostic markers of neuroendocrine tumours (NET) of the lungs is scarce. As sex steroids contribute to cell proliferation in various human tissues, we aimed at characterising the expression of steroid receptors in a broad cohort of probes from NET of the lungs and evaluated their possible prognostic impact. A total of 192 tumour specimens of NET of the lungs were collected, with 58 surgical specimens of typical carcinoids, 42 of atypical carcinoids, 32 of large cell neuroendocrine carcinomas and 60 of small cell lung cancer (SCLC). Analysis by immunohistochemistry for the following antigens was performed: estrogen receptor β (ERβ), ERα, PR (progesterone receptor), AR (androgen receptor), Thyroid transcription factor 1 (TTF1), synaptophysin and for chromograninA. ERβ was found to be expressed in more than 60% of tumor probes. Survival data were available from 126 patients. In SCLC patients a subgroup analysis showed a survival benefit in the group of male patients whose tumours expressed ERβ (p=0.008) and all SCLC patients whose tumours expressed both ERβ and chromograninA (p=0.02). Here we could demonstrate that ERβ expression is frequent through all NET of the lungs. Moreover, our results suggest that ERβ represents a favourable prognostic factor for SCLC male patients and all SCLC patients whose tumors co-expressed chromogranin A.

Leukemia & Lymphoma, 2011

Gene array studies on follicular lymphoma (FL) have associated non-malignant tumor-infiltrating i... more Gene array studies on follicular lymphoma (FL) have associated non-malignant tumor-infiltrating immune cells with patient survival. We examined the role of such cells detectable by immunohistochemistry in a tissue microarray, focusing on plasmacytoid dendritic cells (pDCs). These cells physiologically produce interferon-α, which has been used in the therapy of FL. High numbers of pDCs are associated with increased survival, and so are high numbers of CD3+ T cells. The regular distribution of pDCs within T cell areas is reflected by a weak but significant correlation between pDCs and T cells. However, in multivariate Cox models, CD123 proved to be an independent prognostic factor. These findings support the hypothesis of an association of pDCs with better prognosis by producing interferon. Furthermore, due to a linear relationship between pDCs and survival shown by means of Kaplan-Meier plots, immunohistochemical staining of CD123 could serve as a prognostic tool for patients with FL.

BACKGROUND: Immunodeficiency and AIDS-related pulmonary infections have been suggested as indepen... more BACKGROUND: Immunodeficiency and AIDS-related pulmonary infections have been suggested as independent causes of lung cancer among HIV-infected persons, in addition to smoking. METHODS: A total of 68 lung cancers were identified in the Swiss HIV Cohort Study (SHCS) or through linkage with Swiss Cancer Registries (1985-2010), and were individually matched to 337 controls by centre, gender, HIV-transmission category, age and calendar period. Odds ratios (ORs) were estimated by conditional logistic regression. RESULTS: Overall, 96.2% of lung cancers and 72.9% of controls were ever smokers, confirming the high prevalence of smoking and its strong association with lung cancer (OR for current vs never ¼ 14.4, 95% confidence interval (95% CI): 3.36-62.1). No significant associations were observed between CD4 þ cell count and lung cancer, neither when measured within 1 year (OR for o200 vs X500 ¼ 1.21, 95% CI: 0.49-2.96) nor further back in time, before lung cancer diagnosis. Combined antiretroviral therapy was not significantly associated with lung cancer (OR for ever vs never ¼ 0.67, 95% CI: 0.29-1.52), and nor was a history of AIDS with (OR ¼ 0.49, 95% CI: 0.19-1.28) or without (OR ¼ 0.53, 95% CI: 0.24-1.18) pulmonary involvement. CONCLUSION: Lung cancer in the SHCS does not seem to be clearly associated with immunodeficiency or AIDS-related pulmonary disease, but seems to be attributable to heavy smoking.

Oncotarget, 2016

Objectives: To explore the prognostic role of CK19 expression in squamous cell carcinomas within ... more Objectives: To explore the prognostic role of CK19 expression in squamous cell carcinomas within a well-defined cohort of oral tongue cancer patients. Methods: In our retrospective study, we investigated 129 patients with tongue cancer that had suitable material for inclusion in a tissue microarray (TMA). Where possible, samples were taken from central and peripheral regions of the tumor to generate a representative sample of the tumor. The expression level of CK19 was assessed by immunohistochemical staining. Results: Expression of CK19 in squamous cell carcinoma of the tongue was identified as a negative predictor for overall survival (OS; p<0.000) and disease specific survival (DSS; p=0.001). No significant difference could be shown for disease free survival (DFS) between patients with positive and negative CK19 staining (p=.094). Conclusion: This is the first description of the highly significant role of CK19 in a selective, organ specific head and neck cancer cohort. Our results are of special importance against the background that CK19 positive carcinomas revealed a significantly poorer prognosis and therefore emphasize its prognostic and possible diagnostic role in tongue cancer.

Journal of Neuro-Oncology

Purpose There is large variability in reported incidence rates of primary brain/CNS tumors across... more Purpose There is large variability in reported incidence rates of primary brain/CNS tumors across the world, with mostly higher rates in higher-income countries. The aim was to compare malignant and benign brain/CNS tumor incidence between Zurich (Switzerland), a high-income country, and Georgia, a lower middle-income country. Methods For the period March 2009 to February 2012, we extracted the following tumors based on topography according to ICD-O3: C70.0–C72.9, and C75.1 (pituitary gland). Data were categorized into histology groups based on the WHO 2007 histological classification. Age-standardized rates per 100,000 person-years were calculated by subgroups. Results We included 1104 and 1476 cases of primary brain/CNS tumors for Zurich and Georgia, respectively. Mean age of patients was significantly lower in Georgia compared to Zurich (50.0 versus 58.3 years). Overall age-standardized incidence rates for malignant and benign brain/CNS tumors were 10.5 (95% CI 9.9–11.0) for Geor...

Journal of Clinical Oncology

Journal of Cancer Research and Clinical Oncology

BioMed research international, 2018

Data quality is an important issue in cancer registration. This paper provides a comprehensive ov... more Data quality is an important issue in cancer registration. This paper provides a comprehensive overview of the four main data quality indicators (comparability, validity, timeliness, and completeness) for the Cancer Registry Zurich and Zug (Switzerland). We extracted all malignant cancer cases (excluding non-melanoma skin cancer) diagnosed between 1980 and 2014 in the canton of Zurich. Methods included the proportion of morphologically verified cases (MV%), the proportion of DCN and DCO cases (2009-2014), cases with primary site uncertain (PSU%), the stability of incidence rates over time, age-specific incidence rates for childhood cancer, and mortality:incidence (MI) ratios. The DCO rate decreased from 6.4% in 1997 to 0.8% in 2014 and was <5% since 2000. MV% was 95.5% in 2014. PSU% was <3% over the whole period. The incidence rate of all tumours increased over time with site-specific fluctuations. The overall M:I ratio decreased from 0.58 in 1980 to 0.37 in 2014. Overall, dat...

Cancer medicine, Jan 17, 2018

Cancer of unknown primary (CUP) is a distinct clinicopathological entity with poor prognosis, fre... more Cancer of unknown primary (CUP) is a distinct clinicopathological entity with poor prognosis, frequently resistant to chemotherapy. Comprehensive genomic profiling (CGP) by next-generation sequencing potentially identifies novel treatment options for CUP patients. The objective of this study was to determine incidence and survival trends and to discuss the value of CGP in CUP patients. Age-standardized incidence rates (ASR) per 100 000 were calculated for 2935 CUP patients from 1981 to 2014 using cancer registry data of the canton of Zurich, Switzerland. Kaplan-Meier survival curves were estimated for sex, age, and histological groups. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HR). A literature review was conducted to assess the current use of CGP in CUP patients. ASR of CUP increased from 10.3 to 17.6 between 1981 and 1997 and decreased to 5.8/100 000 in 2014. Mean overall survival remained stable. Mortality was significantly lower for...

Journal of cancer research and clinical oncology, 2018

The aim of this study was to assess the associations of comorbidities with primary treatment of p... more The aim of this study was to assess the associations of comorbidities with primary treatment of prostate cancer (PCa) patients and of comorbidities with PCa-specific mortality (PCSM) compared to other-cause mortality (OCM) in Switzerland. We included 1527 men diagnosed with PCa in 2000 and 2001 in the canton of Zurich. Multiple imputation methods were applied to missing data for stage, grade and comorbidities. Multinomial logistic regression analyses were used to explore the associations of comorbidities with treatment. Cox regression models were used to estimate all-cause mortality, and Fine and Gray competing risk regression models to estimate sub-distribution hazard ratios for the outcomes PCSM and OCM. Increasing age was associated with a decreasing probability of receiving curative treatment, whereas an increasing Charlson Comorbidity Index (CCI) did not influence the treatment decision as strongly as age. The probability of OCM was higher for patients with comorbidities compar...

Urologic oncology, 2018

To assess the risk of prostate cancer (PCa) specific mortality (PCSM) compared to cardiovascular ... more To assess the risk of prostate cancer (PCa) specific mortality (PCSM) compared to cardiovascular disease mortality (CVDM), or other-cause mortality (OCM) of men with nonmetastatic PCa according to PCa risk groups, primary treatment, and age. This retrospective population-based cohort study identified 1,908 nonmetastatic PCa patients in the cancer registry Zurich and Zug, diagnosed between 2000 and 2009 living in the City of Zurich. Multiple imputation methods were applied to handle missing PCa information. Fine and Gray competing risk regression analysis was used to estimate subdistribution hazard ratios for the outcomes PCSM, CVDM, or OCM RESULTS: Ten years after diagnosis the cumulative probability of PCSM and CVDM was 16.4% and 10.0%, respectively. We observed an increased adjusted risk of PCSM in men treated with androgen deprivation therapy (ADT) compared to surgery, but could not observe an association between ADT and CVDM. The probability of PCSM was significantly higher for ...

Cancer causes & control : CCC, 2018

To investigate differences in prostate cancer incidence between two distinct Swiss regions from 1... more To investigate differences in prostate cancer incidence between two distinct Swiss regions from 1996 to 2013 stratified by age group, grade, and T-stage. The dataset included 17,495 men living in Zurich and 3,505 men living in Ticino, diagnosed with prostate cancer between 1996 and 2013. We computed age-standardized incidence rates per 100,000 person-years using the European Standard Population. Trends were assessed using JoinPoint regression analysis Software. Age-standardized incidence rates were generally higher in Zurich compared to Ticino but the difference decreased over time. Incidence rates increased significantly up to 2002 in Zurich and 2007 in Ticino and then decreased. A statistically significant increase was observed for men aged < 65 years, for grade 3 tumors, and for T-stage 2 and 3 tumors. The largest decrease was seen for grade 1 tumors. Furthermore, the incidence of tumors of unknown grade or T-stage decreased significantly in both regions. The trends in prostat...

Oncology Research and Treatment

BACKGROUND: The aim of this study was to assess associations of stage, grade, and age with the pr... more BACKGROUND: The aim of this study was to assess associations of stage, grade, and age with the primary treatment of prostate cancer (PCa) patients comparing the incidence years

Melanoma Research, 2016

The aims of this paper are to describe the incidence trends of invasive cutaneous melanoma in the... more The aims of this paper are to describe the incidence trends of invasive cutaneous melanoma in the Canton of Zurich and to evaluate clinical and pathological factors such as cancer subtype, localization, age and Breslow thickness. A retrospective analysis was carried out with data from the population-based Cancer Registry of Zurich and Zug located in Zurich. A total of 8469 cases in 8034 different patients of invasive cutaneous melanoma were registered for the period 1980-2010 in the Canton of Zurich. Incidence trends were age standardized to the European standard population. Joinpoint regression was used to compute changes in incidence and mortality rates, measured as the annual percent change (APC). The most common subtypes of cutaneous melanoma were superficial spreading melanoma (SSM, 41.1%), followed by nodular melanoma (16.5%), lentigo maligna melanoma (13.5%), acral-lentiginous melanoma (5.0%) and other types of melanoma (2.8%); 21.1% were melanoma not otherwise specified. The trunk was the most frequent location (30.8%), followed by the lower limb and hip (26.4%) and the upper limb and shoulder (22.8%). Statistically significantly increasing incidence trends were observed for both men (APC=3.0%) and women (APC=2.1%). Incidences of SSM and melanoma not otherwise specified were the histological subtypes for which a significant increase in incidence was observed (APC for the period 1980-2010=3.2% for both). In terms of Breslow thickness, thin melanomas (0.01-1.00 mm) showed an increasing incidence. The incidence of melanoma increased in both men and women between 1980 and 2010. In terms of the different subtypes and Breslow thickness, increasing incidences of the SSM and of thin melanomas (0.01-1.00 mm) were observed. These observations are in agreement with other studies from Southern and Western Switzerland as well as other European countries and the USA.