ERCC1 protein, mRNA expression and T19007C polymorphism as prognostic markers in head and neck squamous cell carcinoma patients treated with surgery and adjuvant cisplatin-based chemoradiation

Abstract

Abstract. Adjuvant cisplatin-based chemoradiation improves survival in HNSCC patients presenting with risk features. ERCC1 (excision repair cross-complementation group 1) is associated with resistance to chemo-and radiation therapy and may have a prognostic value in HNSCC patients. Here we studied ERCC1 expression and the polymorphism T19007C as prognostic markers in these patients. This is a retrospective and translational analysis, where ERCC1 protein expression was evaluated by immunohistochemistry, using an H-score, and mRNA expression was determined by RT-PCR. T19007C genotypes were detected by PCR-RFLP carried out using DNA template extracted from normal lymph nodes. A high H-score was seen in 32 patients (54%), who presented better 5-year overall survival (5-y OS: 50% vs. 18%, HR 0.43, p=0.026). Fifteen out of 45 patients (33%), with high mRNA expression, presented better 5-year overall survival (OS) (86% vs. 30%, HR 0.26, p=0.052). No OS difference was detected among T19007C genotypes. High H-score and mRNA expression remained significant as favorable prognostic factors in a multivariate analysis. Collectively, our results suggest that high ERCC1 expression seems to be associated with better OS rates in HNSCC patients submitted to adjuvant cisplatin-based chemoradiation.

Predictive Role of ERCC1 Expression in Head and Neck Squamous Cell Carcinoma Patients Treated with Surgery and Adjuvant Cisplatin-Based Chemoradiation

“…In our cohort of patients, the persistent positive predictive role of ERCC1 for OS can be explained by the use of platinum-based chemotherapy for recurrent inoperable or metastatic disease (data not shown). Our results are in contrast to those published by De Castro et al [14] that demonstrated a better prognosis for HNSCC patients with high ERCC1 expression submitted to adjuvant cisplatin-based chemotherapy. Even though in the two studies the antibody and the IHC scoring systems were the same, the ERCC1 expression described by De Castro et al was low (54%) compared to our results and other reports [10,11].…”

“…An explanation could be that the positive prognostic role of high ERCC1 expression can be counterbalanced by its negative predictive activity, confirming the hypothesis and interpretation on the opposite and not additive role of high ERCC1 expression formulated by others [12]. De Castro et al [14] reported low 5-year OS and DFS rates compared to our study as well as to the EORTC and RTOG studies, and it was explained by a very long median overall treatment time (21 weeks). This recognition might suggest population heterogeneity between the two studies, which makes the results less comparable.…”

“…We know that OS can be influenced by subsequent chemotherapy after adjuvant treatment, and, as a consequence, OS cannot be considered a reliable parameter to assess the predictive value of molecular markers in the adjuvant setting. Another interesting finding is that among the patients classified as having a high risk of recurrence, which were the majority (58%) in the study of De Castro et al [14], ERCC1 expression lost its predictive value. An explanation could be that the positive prognostic role of high ERCC1 expression can be counterbalanced by its negative predictive activity, confirming the hypothesis and interpretation on the opposite and not additive role of high ERCC1 expression formulated by others [12].…”

“…The difference can be explained by a possible underestimation of ERCC1 in the cited study due to the subjective nature of H score quantification. In the study of De Castro et al [14], the positive correlation between high ERCC1 expression and good prognosis is described only for OS, and no data on the correlation with DFS was shown. We know that OS can be influenced by subsequent chemotherapy after adjuvant treatment, and, as a consequence, OS cannot be considered a reliable parameter to assess the predictive value of molecular markers in the adjuvant setting.…”

“…On the other hand, in the only study published on HNSCC patients submitted to adjuvant cisplatin-based chemotherapy, high ERCC1 expression was associated with better prognosis [14]. Thus, the role of ERCC1 in radically resected HNSCC patients treated with surgery and cisplatin-based chemoradiation needs further investigations.…”