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Low ERCC1 expression is associated with prolonged survival in patients with bladder cancer receiving platinum-based neoadjuvant chemotherapy
Authors:Muhammet Fuat Ozcan  Omer Dizdar  Nazmiye Dincer  Serdar Balcı  Gulnur Guler  Bahri Gok  Gokhan Pektas  Mehmet Metin Seker  Sercan Aksoy  Cagatay Arslan  Suayib Yalcin  Mevlana Derya Balbay
Institution:1. Department of Urology, Ankara Ataturk Education and Research Hospital, Ankara, Turkey;2. Department of Medical Oncology, Ankara Ataturk Education and Research Hospital, Ankara, Turkey;3. Department of Pathology, Ankara Ataturk Education and Research Hospital, Ankara, Turkey;4. Department of Internal Medicine, Ankara Ataturk Education and Research Hospital, Ankara, Turkey;5. Department of Medical Oncology, Ankara Numune Education and Research Hospital, Ankara, Turkey;6. Department of Medical Oncology, Hacettepe University Institute of Oncology, Ankara, Turkey
Abstract:PurposeExcision repair cross-complementation group 1 enzyme (ERCC1) plays a key role in the removal of platinum induced DNA adducts and cisplatin resistance. Prognostic role of ERCC1 expression in the neoadjuvant setting in bladder cancer has not been reported before. We evaluated the prognostic role of ERCC1 expression in bladder cancer receiving platinum-based neoadjuvant chemotherapy.Materials and methodsThirty-eight patients with muscle invasive bladder cancer who received neoadjuvant platinum-based chemotherapy were included. Clinical and histopathologic parameters along with immunohistochemical ERCC1 staining were examined and correlated with response rates and survival.ResultsPathologic complete response rates were similar between patients with low and high ERCC1 expression. Median disease-free survival (DFS) was 9.3 vs. 20.5 months (P = 0.186) and median overall survival (OS) was 9.3 vs. 26.7 months (P = 0.058) in patients with high ERCC1 expression compared with those with low expression, respectively. In multivariate Cox regression analysis: pathological complete response (pCR) after chemotherapy (hazard ratio (HR) 0.1, 95% CI 0.012–0.842, P = 0.034) and high ERCC1 expression (HR 3.7, 95% CI 1.2–11.2, P = 0.019) were significantly associated with DFS. Patient age (>60 vs. ≤60 years) (HR 3.4, 95% CI 1.2–9.4, P = 0.018), the presence of pCR (HR 0.11, 95% CI 0.014–0.981, P = 0.048) and high ERCC expression (HR 6.1, 95 CI 1.9–19.9, P = 0.002) were significantly associated with OS.ConclusionsOur results showed that high ERCC1 expression was independently associated with shorter disease-free and overall survival in patients with bladder cancer who received neoadjuvant platinum-based chemotherapy. ERCC1 may represent a potential predictive marker for platinum-based treatment in bladder cancer.
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