Cassio Cardoso-Filho | Universidade Estadual de Campinas (original) (raw)
Papers by Cassio Cardoso-Filho
Tumor Biology, 2019
The objective of this study is to evaluate the relationship between discoidin domain receptor 2 (... more The objective of this study is to evaluate the relationship between discoidin domain receptor 2 (DDR2) and miR-182 expression with response to platinum-based chemotherapy and survival in women with high-grade serous ovarian cancer (HGSOC). We evaluated 78 women with HGSOC stages I-IV, diagnosed between 1996 and 2013, and followed up until 2016. DDR2 expression was assessed using immunohistochemistry on tissue microarray slides. The microRNAs were evaluated by qRT-PCR. DDR2 expression was high in 11 (14.1%) women. PFS was significantly lower in women with FIGO stage I/II-versus III/IV, post-surgery residual disease and high expression of DDR2. Women with postsurgery residual disease, FIGO stage I/II-versus III/IV and DDR2 expression had worse OS, but only post-surgery residual disease remained an independent prognostic factor for worse OS in multivariable analysis. miR-182 expression levels were significantly lower in patients harboring tumors with higher expression of DDR2 (p \ 0.001). In this relatively large cohort of women with HSGOC, higher DDR2 expression was associated with lower miR-182 levels and worse PFS, suggesting that these molecules may be associated with mechanisms of HGSOC progression.
Introduction Breast cancer is a type that more affects female population in the world. Surgical i... more Introduction Breast cancer is a type that more affects female population
in the world. Surgical indication, present in most cases,
is a mutilating procedure and mentally traumatic for majority of
women subjected. Thus, immediate breast reconstruction, which
is the choice to rebuild the breast during the mastectomy surgery,
is an alternative to reduce discomforts associated with loss of the
breast, in addition to being associated potentially with improved
emotional and psychosocial quality of life.
Objective To discuss, from psychological viewpoint, the emotional
expectations about surgical results of a planned mastectomy
with immediate breast reconstruction, reported by women with
breast cancer treated in a university hospital in Campinas, state of
São Paulo.
Method Qualitative design, particularized in the clinicalqualitative
method, adequate to health assistant settings, using
the semi-directed interview with open-ended questions in-depth,
fully transcribed and after submitted to content clinical-qualitative
analysis. Intentional sample closed by criterion of information
theoretical saturation with 12 sequential participants.
Results Amongst the emergent categories from free-floating
readings, we have chosen the following to presentation:.
–The desire of healing above expectations of the aesthetic aspects;
–The perception of the surgical approach predominantly with aesthetic
effects;
–The desire of a contra-lateral healthy breast withdrawal, too.
Conclusions Face the proposal of mastectomy with immediate
reconstruction, days before the surgery, women reported to be
well emotionally organized for the procedure, although in different
ways. This occurs probably due to emotional meanings built
by many experiences from their psychological histories, as well as
from values provided by the socio-cultural environments.
Disclosure of interest The authors have not supplied their declaration
of competing interest.
Purpose Individual differences in cytochrome P-450 efficiency partly explain their variations in ... more Purpose Individual differences in cytochrome P-450 efficiency partly explain their variations in resistance to tamoxifen and estrogen metabolism. Two polymorphisms of the CYP1A1 gene—A4889G and T6235C—are known to affect activation of estrone and estradiol and to deregulate concentration of highly active tamoxifen metabolites. However, the clinicopathologic implications of these findings have not yet been evaluated. Objective The objective of this study is to evaluate whether T6235C and A4889G gene polymorphisms are related to pathological presentations and clinical outcomes of ER?/PR? breast cancer (BC) in women using tamoxifen. Methods We included 405 women with ER?/PR? tumors, who used tamoxifen as their primary therapy, and for whom 5-year follow-up data were available. We evaluated associations within clinicopathologic features, including overall 5-year survival, with CYP1A1 gene status. Results Univariate analysis showed that a slightly higher proportion of women with AG/GG genotypes were of European descent (P = 0.05) and that TC/CC genotype was significantly associated with premenopausal status (P = 0.01); however, no significant association remained after multivariate adjustment. Women with CYP1A1 genotypes other than AA and TT were more prone to develop low-grade tumors; 85.9 % of tumors in AA and TT genotype groups were grade III, but only 76.1 % of tumors in carriers of the polymorphisms were grade III (adjusted P = 0.02; OR 0.51 for grade III disease; 95 % CI 0.28–0.93). After 60 months of follow-up, *75 % of the women were alive. There was no significant difference in survival related to the CYP1A1 gene status. Conclusions Breast cancer patients carrying CYP1A1 gene polymorphisms developed less aggressive tumors, but showed no evidence of better prognoses.
Clinics (São Paulo, Brazil), 2015
We examined the influence of CYP1A1 A4889G and T6235C polymorphisms on the risk of sporadic breas... more We examined the influence of CYP1A1 A4889G and T6235C polymorphisms on the risk of sporadic breast cancer. DNA from 742 sporadic breast cancer patients and 742 controls was analyzed using the polymerase chain reaction, followed by the restriction fragment length polymorphism technique. More patients had the CYP1A1 4889AG+GG genotype compared to controls (29.0% versus 23.2%, p=0.004). The G allele carriers had a 1.50-fold increased risk (95% CI: 1.14-1.97) of sporadic breast cancer compared to the other study participants. The frequency of the 4889AG+GG genotype among the Caucasian patients was higher than in the non-Caucasian patients (30.4% versus 20.2%, p=0.03) and controls (30.4% versus 23.2%, p=0.002). Caucasians and G allele carriers had a 1.61-fold increased risk (95% CI: 1.20-2.15) of sporadic breast cancer compared to other subjects. The CYP1A1 4889AG+GG genotype was more common among patients with a younger median age at first full-term pregnancy than among controls (33.8% ...
![Research paper thumbnail of [Polymorphisms GSTM1 and GSTT1 and sporadic breast cancer mammographic features]](https://attachments.academia-assets.com/42660627/thumbnails/1.jpg)
](Revista da Associação Médica Brasileira (1992)
Enzymes of the Glutathione S-transferase system (GST) modulate the effects of exposure to several... more Enzymes of the Glutathione S-transferase system (GST) modulate the effects of exposure to several cytotoxic and genotoxic agents. The GSTM1 and GSTT1 genes are polymorphic in humans and their deletions have been associated to increased risk of many cancers, including breast cancer. To evaluate the occurrence of homozygous deletions of the GSTM1 and GSTT1 genes in women with sporadic breast cancer and in women without cancer and to compare breast cancer mammographic features between patients with and without these deletions. The study evaluated 100 patients with sporadic breast cancer treated from September 2004 to June 2005 and 169 women without cancer, determining the frequency of the above-mentioned deletions by PCR and calculating the odds ratios and their 95% confidence intervals. Medical files and mammograms of 100 patients with breast cancer were evaluated and correlated with mammographic features such as density, mammographic findings and the BI-RADS classification. These fin...
Cancer Chemotherapy and Pharmacology, 2013
Purpose Individual differences in cytochrome P-450 efficiency partly explain their variations in ... more Purpose Individual differences in cytochrome P-450 efficiency partly explain their variations in resistance to tamoxifen and estrogen metabolism. Two polymorphisms of the CYP1A1 gene-A4889G and T6235C-are known to affect activation of estrone and estradiol and to deregulate concentration of highly active tamoxifen metabolites. However, the clinicopathologic implications of these findings have not yet been evaluated.
ABSTRACT The VEGF C936T and G634C polymorphisms affect the expression of the vascular endothelial... more ABSTRACT The VEGF C936T and G634C polymorphisms affect the expression of the vascular endothelial growth factor (VEGF) gene in breast cancer (BC) cells. The cells also produce the antiangiogenic protein endostatin (ES), product of the COL18A1 gene. COL18A1 D104N polymorphism was associated to increased sporadic BC (SBC) risk. Furthermore, by promoting the glutathione anti-oxidant activity, the glutathione S-transferase (GST) enzymes facilitate the hypoxia factor activity, stimulating the angiogenesis (AG). The GSTM1 wild genotype was associated to a high angiogenic phenotype. The intratumoral microvessel density (IMVD) in tissues is used to quantify the AG. Since it is not well established whether VEGF C936T and G634C, COL18A1 D104N, GSTM1 and GSTT1 polymorphisms alter the risk, VEGF and ES proteins levels and IMVD in SBC, these were the aims of study. DNA from 207 SBC patients and 207 controls was analyzed using PCR-RFLP or multiplex-PCR. ELISA was used for quantification of VEGF in 77 patients and 76 controls and of ES in 117 patients and 107 controls serum samples. The IMVD in neoplastic tissues of 83 patients was determined by immunohistochemistry. Similar frequencies of VEGF C936T, GSTM1 and GSTT1 genotypes were seen in patients and controls. Individuals with these distinct genotypes were under SBC similar risks. In contrast, VEGF 634CC (15.7% vs 8.7%, P= 0.03) and COL18A1 104NN (2.4% vs 0.0%, P= 0.02) genotypes frequencies were higher in patients than in controls. Individuals with these genotypes were under a 1.9-fold (95% CI: 1.1-3.6) and infinite risks for SBC, respectively. Similar VEGF and ES values were found in patients and controls with the genotypes of the respective genes. The IMVD was similar in patients with the VEGF and GST genotypes. However, the IMVD in patients with DD was higher than in those with NN genotypes of the COL18A1 (19.0 and 28.7; P= 0.02). These results suggest that the VEGF 634CC and COL18A1 104NN genotypes increase risk for SBC and the COL18A1 104NN genotype was associated to a high angiogenic phenotype. Since similar serum proteins levels were found in individuals with the distinct genotypes of these polymorphisms, we hypothesized that the variant alleles, C and N, code proteins with abnormal functions on AG. Financial support: FAPESP and CNPq.
Sao Paulo Medical Journal, 2005
CONTEXT: Supernumerary breast tissue may be affected by the same diseases and alterations that co... more CONTEXT: Supernumerary breast tissue may be affected by the same diseases and alterations that compromise topical breast tissue. Nevertheless, reports of fibroadenoma in supernumerary breast tissue in the axillae are rare. OBJECTIVE: To describe a case of fibroadenoma in an axillary supernumerary breast. DESIGN: Case report. CASE REPORT: A 39-year-old woman was referred to the gynecology and obstetrics outpatient clinic at Hospital Estadual Sumaré, complaining of bilateral axillary masses. The patient reported cosmetic problems and local pain and discomfort. On physical examination, alterations compatible with bilateral axillary accessory breasts, without palpable nodules, were observed. Supplementary examinations (mammography and ultrasonography) revealed a 1.1 cm mass in the right axillary breast. The patient underwent resection of the supernumerary breasts and histopathological examination revealed fibroadenoma of the right axillary breast tissue.
Oncology Reviews, 2008
There is a lack of consensus about the influence of GST M1/T1 gene deletions (DEL) on sporadic br... more There is a lack of consensus about the influence of GST M1/T1 gene deletions (DEL) on sporadic breast cancer (SBC). To evaluate the occurrence of DEL in 177 SBC cases and in 169 controls, and compare clinical and biological characteristics. A lower frequency of GSTM1 DEL was observed in mulatto women, OR=0.48 (0.24–0.98). The risk of nuclear grade 3 tumors (GN3) was lower in patients with GSTT1 DEL, OR=0.37 (0.15–0.90). DEL of at least one gene (ALOG) was associated with women who had not breastfed, OR=0.41 (0.19–0.88), and with negative hormone receptor, HR−, ORadj=2.25 (1.03–4.90). Both genes deleted (BGD) was associated with non-classic invasive ductal carcinoma (NCDC), ORadj=12.09 (1.03–142.03). Mulatto women with SBC had a lower frequency of GSTM1 DEL, while tumors differentiated were related to GSTT1 DEL. HR-tumors were related with DEL ALOG, and the BGD was associated with a greater risk of NCDC.
Revista Da Associacao Medica Brasileira, 2008
INTRODUÇÃO: As enzimas do sistema da glutationa S-transferase (GST) modulam os efeitos da exposiç... more INTRODUÇÃO: As enzimas do sistema da glutationa S-transferase (GST) modulam os efeitos da exposição a vários agentes citotóxicos e genotóxicos. Os genes GSTM1 e GSTT1 são polimórficos em humanos e suas deleções têm sido associadas ao aumento do risco de várias neoplasias, dentre elas o câncer de mama. OBJETIVO: Comparar a freqüência das deleções dos genes GSTM1 e GSTT1 em mulheres sadias e com câncer de mama e comparar as características mamográficas do câncer entre mulheres portadoras e não portadoras das referidas deleções. MÉTODOS: Foram determinadas as freqüências das referidas deleções por PCR em 100 pacientes portadoras de câncer de mama esporádico tratadas de setembro de 2004 a junho de 2005 e em 169 mulheres sadias doadoras de sangue no mesmo período e comparadas através do odds ratio (OR) com seus respectivos IC 95%. Foram revistos os prontuários e as mamografias das pacientes com câncer e avaliadas características mamográficas (padrão de distribuição do parênquima fibro-glandular, achados mamográficos ao diagnóstico e classificação BI-RADS), correlacionando-as às deleções gênicas através do cálculo da RP (razão de prevalência) com seus respectivos IC 95%. RESULTADOS: O GSTM1 esteve deletado em 40% dos cânceres e em 44,4% dos controles (OR=1,20; IC 95% 0,70-2,04; p=0,5659) enquanto o GSTT1 em 20% e 19,5%, respectivamente (OR=0,73; IC 0,37-1,44; p=0,4124). O padrão mamográfico denso esteve associado à deleção homozigótica do GSTM1 (RP= 2,43; IC 1,11-4,08). Não se observou associação entre as deleções do sistema GST e achados mamográficos ao diagnóstico e classificação BI-RADS. CONCLUSÃO: A deleção homozigótica do gene GSTM1 associou-se ao padrão mamográfico denso.
Tumor Biology, 2010
It is well established that hypoxic microenvironment contributes to breast cancer progression by ... more It is well established that hypoxic microenvironment contributes to breast cancer progression by activation of transcriptional genes that promote angiogenesis. By promoting the antioxidant activity of glutathione, glutathione S-transferases (GSTs) are likely to facilitate the hypoxia-inducible factor-1α (HIF-1α) activity, therefore stimulating the angiogenesis. We investigated herein the influence of the GSTM1 and GSTT1 polymorphisms in the intratumoral angiogenesis of 87 patients with sporadic breast cancer. The intratumoral microvessel density (IMVD) of formalin-fixed paraffin-embedded tissues samples from all patients was determined by immunohistochemistry. The high IMVD was defined as a median microvessel counting higher than 18.7 after the analysis of histogram with all the results. The high IMVD was more common in patients with the GSTT1 wild genotype than in those with the GSTT1 null genotype (P = 0.04). Our results suggest, for the first time, that the GSTT1 polymorphism constitutes an inherited determinant of intratumoral angiogenesis in sporadic breast cancer.
Tumor Biology, 2011
The wild and the variant alleles of the C936T and G634C vascular endothelial grow factor (VEGF) p... more The wild and the variant alleles of the C936T and G634C vascular endothelial grow factor (VEGF) polymorphisms seem to be linked to higher angiogenic phenotype than the remaining alleles and may act on breast cancer (BC) origin. We investigated the influence of the VEGF C936T and G634C polymorphisms on the occurrence and clinicopathologic characteristics of sporadic breast cancer (SBC) in 235 patients and 235 controls. Peripheral blood samples of all individuals were analysed by the polymerase chain reaction for identification of genotypes and by enzyme-linked immunosorbent assay (ELISA) for quantification of serum VEGF levels. The variant 634CC genotype isolated (16.2% versus 10.7%, P = 0.01) and in combination with the wild 936CC genotype (10.6% versus 5.5%, P = 0.01) were more common in patients than in controls. The carriers of the respective genotypes were under a 2.20-fold and a 3.08-fold increased risks for the disease. Additionally, the frequency of the wild 936CC genotype was higher in patients with tumours of histological grade III compared to those with tumours of I+II histological grades (84.0% versus 64.7%, P = 0.004) and in patients with positive oestrogen receptor tumours compared to those with tumours lacking oestrogen receptor expression (84.7% versus 73.9%, P = 0.02). Similar serum values of VEGF were seen in patients and controls with the distinct genotypes of the VEGF. The data suggest that the VEGF wild 936CC and the variant 634CC genotypes constitute inherited determinants of SBC and SBC aggressiveness in Brazil, but are not significant predictors of circulating VEGF levels.
Breast Cancer Research and Treatment, 2006
We investigated the influence of the polymorphism D104N of the COL18A1 gene, encoding endostatin,... more We investigated the influence of the polymorphism D104N of the COL18A1 gene, encoding endostatin, on the occurrence of sporadic breast cancer in 181 patients and 448 controls. The homozygous 104NN polymorphism was found in five patients but was absent in controls (2.8% vs 0.0%; P = 0.002). Individuals with this genotype had a significantly increased risk for disease. Our results suggest, for the first time, that the homozygous 104NN polymorphism, even at low frequency, constitutes an important inherited determinant of the disease.
Tumor Biology, 2019
The objective of this study is to evaluate the relationship between discoidin domain receptor 2 (... more The objective of this study is to evaluate the relationship between discoidin domain receptor 2 (DDR2) and miR-182 expression with response to platinum-based chemotherapy and survival in women with high-grade serous ovarian cancer (HGSOC). We evaluated 78 women with HGSOC stages I-IV, diagnosed between 1996 and 2013, and followed up until 2016. DDR2 expression was assessed using immunohistochemistry on tissue microarray slides. The microRNAs were evaluated by qRT-PCR. DDR2 expression was high in 11 (14.1%) women. PFS was significantly lower in women with FIGO stage I/II-versus III/IV, post-surgery residual disease and high expression of DDR2. Women with postsurgery residual disease, FIGO stage I/II-versus III/IV and DDR2 expression had worse OS, but only post-surgery residual disease remained an independent prognostic factor for worse OS in multivariable analysis. miR-182 expression levels were significantly lower in patients harboring tumors with higher expression of DDR2 (p \ 0.001). In this relatively large cohort of women with HSGOC, higher DDR2 expression was associated with lower miR-182 levels and worse PFS, suggesting that these molecules may be associated with mechanisms of HGSOC progression.
Introduction Breast cancer is a type that more affects female population in the world. Surgical i... more Introduction Breast cancer is a type that more affects female population
in the world. Surgical indication, present in most cases,
is a mutilating procedure and mentally traumatic for majority of
women subjected. Thus, immediate breast reconstruction, which
is the choice to rebuild the breast during the mastectomy surgery,
is an alternative to reduce discomforts associated with loss of the
breast, in addition to being associated potentially with improved
emotional and psychosocial quality of life.
Objective To discuss, from psychological viewpoint, the emotional
expectations about surgical results of a planned mastectomy
with immediate breast reconstruction, reported by women with
breast cancer treated in a university hospital in Campinas, state of
São Paulo.
Method Qualitative design, particularized in the clinicalqualitative
method, adequate to health assistant settings, using
the semi-directed interview with open-ended questions in-depth,
fully transcribed and after submitted to content clinical-qualitative
analysis. Intentional sample closed by criterion of information
theoretical saturation with 12 sequential participants.
Results Amongst the emergent categories from free-floating
readings, we have chosen the following to presentation:.
–The desire of healing above expectations of the aesthetic aspects;
–The perception of the surgical approach predominantly with aesthetic
effects;
–The desire of a contra-lateral healthy breast withdrawal, too.
Conclusions Face the proposal of mastectomy with immediate
reconstruction, days before the surgery, women reported to be
well emotionally organized for the procedure, although in different
ways. This occurs probably due to emotional meanings built
by many experiences from their psychological histories, as well as
from values provided by the socio-cultural environments.
Disclosure of interest The authors have not supplied their declaration
of competing interest.
Purpose Individual differences in cytochrome P-450 efficiency partly explain their variations in ... more Purpose Individual differences in cytochrome P-450 efficiency partly explain their variations in resistance to tamoxifen and estrogen metabolism. Two polymorphisms of the CYP1A1 gene—A4889G and T6235C—are known to affect activation of estrone and estradiol and to deregulate concentration of highly active tamoxifen metabolites. However, the clinicopathologic implications of these findings have not yet been evaluated. Objective The objective of this study is to evaluate whether T6235C and A4889G gene polymorphisms are related to pathological presentations and clinical outcomes of ER?/PR? breast cancer (BC) in women using tamoxifen. Methods We included 405 women with ER?/PR? tumors, who used tamoxifen as their primary therapy, and for whom 5-year follow-up data were available. We evaluated associations within clinicopathologic features, including overall 5-year survival, with CYP1A1 gene status. Results Univariate analysis showed that a slightly higher proportion of women with AG/GG genotypes were of European descent (P = 0.05) and that TC/CC genotype was significantly associated with premenopausal status (P = 0.01); however, no significant association remained after multivariate adjustment. Women with CYP1A1 genotypes other than AA and TT were more prone to develop low-grade tumors; 85.9 % of tumors in AA and TT genotype groups were grade III, but only 76.1 % of tumors in carriers of the polymorphisms were grade III (adjusted P = 0.02; OR 0.51 for grade III disease; 95 % CI 0.28–0.93). After 60 months of follow-up, *75 % of the women were alive. There was no significant difference in survival related to the CYP1A1 gene status. Conclusions Breast cancer patients carrying CYP1A1 gene polymorphisms developed less aggressive tumors, but showed no evidence of better prognoses.
Clinics (São Paulo, Brazil), 2015
We examined the influence of CYP1A1 A4889G and T6235C polymorphisms on the risk of sporadic breas... more We examined the influence of CYP1A1 A4889G and T6235C polymorphisms on the risk of sporadic breast cancer. DNA from 742 sporadic breast cancer patients and 742 controls was analyzed using the polymerase chain reaction, followed by the restriction fragment length polymorphism technique. More patients had the CYP1A1 4889AG+GG genotype compared to controls (29.0% versus 23.2%, p=0.004). The G allele carriers had a 1.50-fold increased risk (95% CI: 1.14-1.97) of sporadic breast cancer compared to the other study participants. The frequency of the 4889AG+GG genotype among the Caucasian patients was higher than in the non-Caucasian patients (30.4% versus 20.2%, p=0.03) and controls (30.4% versus 23.2%, p=0.002). Caucasians and G allele carriers had a 1.61-fold increased risk (95% CI: 1.20-2.15) of sporadic breast cancer compared to other subjects. The CYP1A1 4889AG+GG genotype was more common among patients with a younger median age at first full-term pregnancy than among controls (33.8% ...
Revista da Associação Médica Brasileira (1992)
Enzymes of the Glutathione S-transferase system (GST) modulate the effects of exposure to several... more Enzymes of the Glutathione S-transferase system (GST) modulate the effects of exposure to several cytotoxic and genotoxic agents. The GSTM1 and GSTT1 genes are polymorphic in humans and their deletions have been associated to increased risk of many cancers, including breast cancer. To evaluate the occurrence of homozygous deletions of the GSTM1 and GSTT1 genes in women with sporadic breast cancer and in women without cancer and to compare breast cancer mammographic features between patients with and without these deletions. The study evaluated 100 patients with sporadic breast cancer treated from September 2004 to June 2005 and 169 women without cancer, determining the frequency of the above-mentioned deletions by PCR and calculating the odds ratios and their 95% confidence intervals. Medical files and mammograms of 100 patients with breast cancer were evaluated and correlated with mammographic features such as density, mammographic findings and the BI-RADS classification. These fin...
Cancer Chemotherapy and Pharmacology, 2013
Purpose Individual differences in cytochrome P-450 efficiency partly explain their variations in ... more Purpose Individual differences in cytochrome P-450 efficiency partly explain their variations in resistance to tamoxifen and estrogen metabolism. Two polymorphisms of the CYP1A1 gene-A4889G and T6235C-are known to affect activation of estrone and estradiol and to deregulate concentration of highly active tamoxifen metabolites. However, the clinicopathologic implications of these findings have not yet been evaluated.
ABSTRACT The VEGF C936T and G634C polymorphisms affect the expression of the vascular endothelial... more ABSTRACT The VEGF C936T and G634C polymorphisms affect the expression of the vascular endothelial growth factor (VEGF) gene in breast cancer (BC) cells. The cells also produce the antiangiogenic protein endostatin (ES), product of the COL18A1 gene. COL18A1 D104N polymorphism was associated to increased sporadic BC (SBC) risk. Furthermore, by promoting the glutathione anti-oxidant activity, the glutathione S-transferase (GST) enzymes facilitate the hypoxia factor activity, stimulating the angiogenesis (AG). The GSTM1 wild genotype was associated to a high angiogenic phenotype. The intratumoral microvessel density (IMVD) in tissues is used to quantify the AG. Since it is not well established whether VEGF C936T and G634C, COL18A1 D104N, GSTM1 and GSTT1 polymorphisms alter the risk, VEGF and ES proteins levels and IMVD in SBC, these were the aims of study. DNA from 207 SBC patients and 207 controls was analyzed using PCR-RFLP or multiplex-PCR. ELISA was used for quantification of VEGF in 77 patients and 76 controls and of ES in 117 patients and 107 controls serum samples. The IMVD in neoplastic tissues of 83 patients was determined by immunohistochemistry. Similar frequencies of VEGF C936T, GSTM1 and GSTT1 genotypes were seen in patients and controls. Individuals with these distinct genotypes were under SBC similar risks. In contrast, VEGF 634CC (15.7% vs 8.7%, P= 0.03) and COL18A1 104NN (2.4% vs 0.0%, P= 0.02) genotypes frequencies were higher in patients than in controls. Individuals with these genotypes were under a 1.9-fold (95% CI: 1.1-3.6) and infinite risks for SBC, respectively. Similar VEGF and ES values were found in patients and controls with the genotypes of the respective genes. The IMVD was similar in patients with the VEGF and GST genotypes. However, the IMVD in patients with DD was higher than in those with NN genotypes of the COL18A1 (19.0 and 28.7; P= 0.02). These results suggest that the VEGF 634CC and COL18A1 104NN genotypes increase risk for SBC and the COL18A1 104NN genotype was associated to a high angiogenic phenotype. Since similar serum proteins levels were found in individuals with the distinct genotypes of these polymorphisms, we hypothesized that the variant alleles, C and N, code proteins with abnormal functions on AG. Financial support: FAPESP and CNPq.
Sao Paulo Medical Journal, 2005
CONTEXT: Supernumerary breast tissue may be affected by the same diseases and alterations that co... more CONTEXT: Supernumerary breast tissue may be affected by the same diseases and alterations that compromise topical breast tissue. Nevertheless, reports of fibroadenoma in supernumerary breast tissue in the axillae are rare. OBJECTIVE: To describe a case of fibroadenoma in an axillary supernumerary breast. DESIGN: Case report. CASE REPORT: A 39-year-old woman was referred to the gynecology and obstetrics outpatient clinic at Hospital Estadual Sumaré, complaining of bilateral axillary masses. The patient reported cosmetic problems and local pain and discomfort. On physical examination, alterations compatible with bilateral axillary accessory breasts, without palpable nodules, were observed. Supplementary examinations (mammography and ultrasonography) revealed a 1.1 cm mass in the right axillary breast. The patient underwent resection of the supernumerary breasts and histopathological examination revealed fibroadenoma of the right axillary breast tissue.
Oncology Reviews, 2008
There is a lack of consensus about the influence of GST M1/T1 gene deletions (DEL) on sporadic br... more There is a lack of consensus about the influence of GST M1/T1 gene deletions (DEL) on sporadic breast cancer (SBC). To evaluate the occurrence of DEL in 177 SBC cases and in 169 controls, and compare clinical and biological characteristics. A lower frequency of GSTM1 DEL was observed in mulatto women, OR=0.48 (0.24–0.98). The risk of nuclear grade 3 tumors (GN3) was lower in patients with GSTT1 DEL, OR=0.37 (0.15–0.90). DEL of at least one gene (ALOG) was associated with women who had not breastfed, OR=0.41 (0.19–0.88), and with negative hormone receptor, HR−, ORadj=2.25 (1.03–4.90). Both genes deleted (BGD) was associated with non-classic invasive ductal carcinoma (NCDC), ORadj=12.09 (1.03–142.03). Mulatto women with SBC had a lower frequency of GSTM1 DEL, while tumors differentiated were related to GSTT1 DEL. HR-tumors were related with DEL ALOG, and the BGD was associated with a greater risk of NCDC.
Revista Da Associacao Medica Brasileira, 2008
INTRODUÇÃO: As enzimas do sistema da glutationa S-transferase (GST) modulam os efeitos da exposiç... more INTRODUÇÃO: As enzimas do sistema da glutationa S-transferase (GST) modulam os efeitos da exposição a vários agentes citotóxicos e genotóxicos. Os genes GSTM1 e GSTT1 são polimórficos em humanos e suas deleções têm sido associadas ao aumento do risco de várias neoplasias, dentre elas o câncer de mama. OBJETIVO: Comparar a freqüência das deleções dos genes GSTM1 e GSTT1 em mulheres sadias e com câncer de mama e comparar as características mamográficas do câncer entre mulheres portadoras e não portadoras das referidas deleções. MÉTODOS: Foram determinadas as freqüências das referidas deleções por PCR em 100 pacientes portadoras de câncer de mama esporádico tratadas de setembro de 2004 a junho de 2005 e em 169 mulheres sadias doadoras de sangue no mesmo período e comparadas através do odds ratio (OR) com seus respectivos IC 95%. Foram revistos os prontuários e as mamografias das pacientes com câncer e avaliadas características mamográficas (padrão de distribuição do parênquima fibro-glandular, achados mamográficos ao diagnóstico e classificação BI-RADS), correlacionando-as às deleções gênicas através do cálculo da RP (razão de prevalência) com seus respectivos IC 95%. RESULTADOS: O GSTM1 esteve deletado em 40% dos cânceres e em 44,4% dos controles (OR=1,20; IC 95% 0,70-2,04; p=0,5659) enquanto o GSTT1 em 20% e 19,5%, respectivamente (OR=0,73; IC 0,37-1,44; p=0,4124). O padrão mamográfico denso esteve associado à deleção homozigótica do GSTM1 (RP= 2,43; IC 1,11-4,08). Não se observou associação entre as deleções do sistema GST e achados mamográficos ao diagnóstico e classificação BI-RADS. CONCLUSÃO: A deleção homozigótica do gene GSTM1 associou-se ao padrão mamográfico denso.
Tumor Biology, 2010
It is well established that hypoxic microenvironment contributes to breast cancer progression by ... more It is well established that hypoxic microenvironment contributes to breast cancer progression by activation of transcriptional genes that promote angiogenesis. By promoting the antioxidant activity of glutathione, glutathione S-transferases (GSTs) are likely to facilitate the hypoxia-inducible factor-1α (HIF-1α) activity, therefore stimulating the angiogenesis. We investigated herein the influence of the GSTM1 and GSTT1 polymorphisms in the intratumoral angiogenesis of 87 patients with sporadic breast cancer. The intratumoral microvessel density (IMVD) of formalin-fixed paraffin-embedded tissues samples from all patients was determined by immunohistochemistry. The high IMVD was defined as a median microvessel counting higher than 18.7 after the analysis of histogram with all the results. The high IMVD was more common in patients with the GSTT1 wild genotype than in those with the GSTT1 null genotype (P = 0.04). Our results suggest, for the first time, that the GSTT1 polymorphism constitutes an inherited determinant of intratumoral angiogenesis in sporadic breast cancer.
Tumor Biology, 2011
The wild and the variant alleles of the C936T and G634C vascular endothelial grow factor (VEGF) p... more The wild and the variant alleles of the C936T and G634C vascular endothelial grow factor (VEGF) polymorphisms seem to be linked to higher angiogenic phenotype than the remaining alleles and may act on breast cancer (BC) origin. We investigated the influence of the VEGF C936T and G634C polymorphisms on the occurrence and clinicopathologic characteristics of sporadic breast cancer (SBC) in 235 patients and 235 controls. Peripheral blood samples of all individuals were analysed by the polymerase chain reaction for identification of genotypes and by enzyme-linked immunosorbent assay (ELISA) for quantification of serum VEGF levels. The variant 634CC genotype isolated (16.2% versus 10.7%, P = 0.01) and in combination with the wild 936CC genotype (10.6% versus 5.5%, P = 0.01) were more common in patients than in controls. The carriers of the respective genotypes were under a 2.20-fold and a 3.08-fold increased risks for the disease. Additionally, the frequency of the wild 936CC genotype was higher in patients with tumours of histological grade III compared to those with tumours of I+II histological grades (84.0% versus 64.7%, P = 0.004) and in patients with positive oestrogen receptor tumours compared to those with tumours lacking oestrogen receptor expression (84.7% versus 73.9%, P = 0.02). Similar serum values of VEGF were seen in patients and controls with the distinct genotypes of the VEGF. The data suggest that the VEGF wild 936CC and the variant 634CC genotypes constitute inherited determinants of SBC and SBC aggressiveness in Brazil, but are not significant predictors of circulating VEGF levels.
Breast Cancer Research and Treatment, 2006
We investigated the influence of the polymorphism D104N of the COL18A1 gene, encoding endostatin,... more We investigated the influence of the polymorphism D104N of the COL18A1 gene, encoding endostatin, on the occurrence of sporadic breast cancer in 181 patients and 448 controls. The homozygous 104NN polymorphism was found in five patients but was absent in controls (2.8% vs 0.0%; P = 0.002). Individuals with this genotype had a significantly increased risk for disease. Our results suggest, for the first time, that the homozygous 104NN polymorphism, even at low frequency, constitutes an important inherited determinant of the disease.