Evaluation of the <i>BRCA</i>1/2 mutation as a prognostic marker in primary peritoneal serous cancer

Abstract

Introduction: The present study was a retrospective investigation of the relation between immunohistochemical BRCA1/2 status and prognosis in patients with primary peritoneal serous cancer (PPSC). Materials and Methods: We retrospectively evaluated 14 consecutive patients diagnosed with PPSC other than hereditary breast and ovarian cancer between 2005 and 2010. All patients had serum CA125 levels >40 U/mL prior to starting first-line chemotherapy with paclitaxel and carboplatin. Paclitaxel was administered as a 3-hour intravenous infusion at a dose of 175 mg/m 2 on day 1, and carboplatin was delivered at an area under the curve of 5 based on the Calvert method. Patients received six cycles of first-line chemotherapy, except patients whose disease was determined to be progressive during the chemotherapy regimen. BRCA1/2 and p53 protein expression was determined by immunohistochemistry of patient tissue samples. The Cox proportional hazards model was used to evaluate univariate and independent multivariate associations with the effect of clinical parameters, such as age at diagnosis; tumor histology; tumor grade; and rate of change in CA125, and BRCA1/2, p53 status on overall survival. Probability values of less than 0.05 were considered to indicate statistical significance. Results: Two cases (14%) had the BRCA1 mutation, and none had the BRCA2 mutation. Eleven cases (79%) were positive for p53. In the univariate analysis, factors significantly associated with overall survival were (pre-chemotherapy CA125-pre-2nd chemotherapy CA125)/pre-chemotherapy CA125 (p = 0.0034) and (pre-chemotherapy CA125-pre-3rd chemotherapy CA125)/pre-chemotherapy CA125 (p = 0.0245). BRCA1 and p53 status were not predictors of overall survival. Multivariate analysis performed with overall survival as an endpoint revealed that none of the factors examined was significant. Median survival rate of patients without a BRCA1 mutation was 23.5 months (2 -82 months), and all died. By contrast, one patient with a BRCA1 mutation remains alive at 85 months, and the other patient died at 64 months. Conclusion: BRCA1 might be a predictor of overall survival in patients with PPSC receiving chemotherapy.

Expressão de BRCA1 e BRCA2 por imuno-histoquímica e prognóstico no câncer de ovário: uma revisão sistemática e meta-análise

“…Os dados das análises de SG e SLP de cada estudo para a meta-análise foram obtidos pelos HRs com seus respectivos IC de 95% extraídos diretamente de cada estudo original. BAI et al, 2014;BALDWIN et al, 2000;CARSER et al, 2011;CHO et al, 2015;FERNÁNDEZ et al, 2017;FURUKAWA et al, 2013;GAN et al, 2013;GÜNEŞ;YILMAZ;UZUNLAR, 2007;HJORTKJAER et al, 2017;JU et al, 2016;KAERN et al, 2005;KASHIMA et al, 2000;LESNOCK et al, 2013;LI et al, 2017;MCALPINE et al, 2012;MCMILLEN et al, 2012;MEISEL et al, 2014;NOMURA et al, 2016;POPOVSKA et al, 2014;PRADJATMO et al, 2014;PRESS et al, 2008;RADOSA et al, 2011;RUSSELL et al, 2000;SALLUM et al, 2018;SHAWKY et al, 2014;SHILPA et Resultados ________________________________________________________________ al., 2014;SIRISABYA et al, 2007;SKYTTE et al, 2011;STRICKLAND et al, 2016;SUN et al, 2016;SWISHER et al, 2009;THRALL et al, 2006;VAZ et al, 2007;VORRIUS et al, 2009;WANG C. et al, 2004;WANG et al, 2015aWANG et al, , 2015b…”

“…pacientes (FURUKAWA et al, 2013;LI et al, 2017;SUN et al, 2016;SWISHER et al, 2009;WANG et al, 2015b;YANG et al, 2011bYANG et al, , 2010, um estudo (10,0%) investigou a relação entre a expressão de BRCA2 com as características clínico-patológicas de 161…”

“…Os Três estudos foram excluídos da meta-análise porque a estimativa da HR não foi possível (FURUKAWA et al, 2013;KAERN et al, 2005;SIRISABYA et al, 2007). As…”

“…Gráfico 12 -Análise multivariada para sobrevida global e tumor seroso de alto grau (CARSER et al, 2011;CHO et al, 2015;FURUKAWA et al, 2013;GAN et al, 2013;HJORTKJAER et al, 2017;KAERN et al, 2005;LESNOCK et al, 2013;LI et al, 2017;MCMILLEN et al, 2012;NOMURA et al, 2016;PRADJATMO et al, 2014;RADOSA et al, 2011;SALLUM et al, 2018;SHAWKY et al, 2014;SIRISABYA et al, 2007;SUN et al, 2016;SWISHER et al, 2009;THRALL et al, 2006;WEBERPALS et al, 2011;ZHANG et al, 2015) e BRCA2 (FURUKAWA et al, 2013LI et al, 2017;SUN et al, 2016;SWISHER et al, 2009;WANG et al, 2015b;YANG et al, 2011bYANG et al, , 2010 por IHQ foram estudados em diversos tumores malignos de ovário. Estudos envolvendo pacientes com carcinoma epitelial de ovário sugeriram que a ausência ou a perda de expressão de BRCA1 (CARSER et al, 2011;GARG et al, 2013;HJORTKJAER et al, 2017;KASHIMA et al, 2000KASHIMA et al, , 2000KUHN;AYHAN, 2018;MEISEL et al, 2014;SUN et al, 2016;YANG et al, 2011bYANG et al, , 2010 foi um biomarcador prognóstico ou preditivo…”

“…Em pacientes com carcinoma epitelial de ovário, a expressão reduzida de BRCA1 detectada por IHQ ou por metilação da região promotora do gene BRCA1 mostrou-se como importante ferramenta de utilidade clínica para promover informação prognóstica (GARG et al, 2013;WEBERPALS et al, 2011). No entanto, as evidências científicas são contraditórias na demonstração do valor prognóstico da perda de expressão de BRCA1 ou BRCA2 por IHQ no carcinoma epitelial de ovário (FURUKAWA et al, 2013;KAERN et al, 2005;SIRISABYA et al, 2007). E diversos avanços terapêuticos ainda não resultaram em mudanças significativas na abordagem das pacientes (GARG et al, 2013;WEBERPALS et al, 2011).…”