Double-staining Immunohistochemistry Reveals in Malignant Pleural Mesothelioma the Coexpression of ERCC1 and RRM1 as a Frequent Biological Event Related to Poorer Survival

Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. To date, standard MPM therapy is still limited to surgery, radiotherapy, and chemotherapy, including pemetrexed and platinum compounds. The main mechanisms of platinum resistance are associated with DNA repair pathways. Excision repair cross-complementing group 1 (ERCC1) and ribonucleotide reductase subunit M1 (RRM1) are important components of the DNA repair, considered as prognostic and predictive biomarkers in various cancer types. The main goal of the present study was to investigate the ERCC1 and RRM1 expression and their potential impact on outcome in this tumor. A series of 73 MPM, mainly treated with a platin-based regimen, was collected and the immunohistochemistry tests were performed to assess ERCC1 and RRM1 expression. In addition, a multiplex immunohistochemistry has been validated to detect simultaneously the 2 proteins on the same slide. In our series, 36 of 73 cases showed ERCC1 expression and 55 of 73 showed RRM1 expression. The double immunohistochemical staining showed the coexpression of ERCC1/RRM1 in 34 of 73 cases. A significant association between ERCC1 and RRM1 expression was observed in our series (P<0.05). Patients with ERCC1/RRM1 coexpression experienced shorter median overall survival (6.6 vs. 13.8 mo, log-rank=7688; P=0.006). Our results suggest that the coexpression of ERCC1/RRM1 could define a group of MPM patients with the worst prognosis who should need likely alternative treatment. In conclusion, we propose the putative usefulness of ERCC1/RRM1 coexpression as prognostic biomarkers for overall survival in MPM.