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Translationale Biomedizin

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Abstrakt

Excision Repair Cross Complementing Group 1 (Ercc1): An Independent Prognostic Marker for Endometrial and Ovarian Cancer

Jun Zhou, Xin Li, Baraa Alosh, Agnes Malysa, Wei Chen, Gerold Bepler, Rouba AF

Most ovarian cancers are epithelial in nature (EOC), and the US annual deaths from the disease exceed all other gynecological cancer deaths combined. In endometrial carcinoma (EC), the International Federation of Gynecology and Obstetrics (FIGO) staging and grading provides the basis for treatment selection and outcomes prediction. Excision repair cross complementing group 1 (ERCC1) is involved in DNA synthesis and repair and has been reported as a prognostic and a predictive marker of platinum efficacy in lung cancer patients among others. We investigated the clinical significance of this marker in EC and EOC.

Archived cases of EC (421) and EOC (198) were reviewed, and analyzed for ERCC1 protein levels with immunofluorescence staining (Automated Quantitative Analysis, AQUA). The average levels from replicate cores were used to determine cutoff points using log-rank testing on overall survival (OS). Kaplan-Meier survival curve with log rank test and multivariable Cox regression analysis were performed to evaluate the prognostic role of ERCC1.

Patients with high ERCC1 levels had significantly longer OS than those with low ERCC1 for both EC (P=0.013) and ovarian cancer (P=0.007). Multivariable COX regression analysis also revealed that high ERCC1 expression was associated with better OS rates in EC (P=0.031) and ovarian cancer (P=0.267). While type- II tumors and FIGO stage III-IV tumors could not be subdivided into good and poor survival groups based on ERCC1 levels, patients with high ERCC1 levels had better OS compared to those with low levels for both type-I tumors (P=0.014) and FIGO stage I-II tumors (P=0.037). Exclusion of patients treated with neoadjuvant chemoradiotherapy yielded similar results. In conclusion, ERCC1 is an independent prognostic factor of OS in endometrial and ovarian cancers. These studies require independent validation and may provide a basis for future molecular classification and treatment decision making.