FRMD6 expression can predict relapse of colorectal carcinoma after cytoreductive surgery with HIPEC.

4.1-ezrin-radixin-moesin (FERM) domain containing protein 6 (FRMD6), a component of Hippo/YAP pathway, behaves as a tumor suppressor gene and is one of the proteins used for colorectal carcinomas (CRC) molecular classification. As its potential prognostic role has not been widely analyzed, this study aims to determine it in the management of CRC with peritoneal involvement. Clinicopathological data from 37 patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for CRC with peritoneal involvement after preoperative chemotherapy, were collected and immunohistochemistry for FRMD6 in preoperative samples was performed. After neoadjuvant chemotherapy, 5 patients achieved pathologic complete response.

After CRS/HIPEC, disease progressed in 66.7% of the patients and at the time of the study 48.6% had died of disease. FRMD6 expression was positive in 45.9% of cases. Statistical analysis revealed a significant association between FRMD6 expression and prognosis both in terms of progression free survival and overall survival and a tendency to significance for the association with pathological response to therapy.

Our results align with the few previous studies findings, which have shown a better prognosis for patients overexpressing FRMD6, but for the first time in the world literature we have analyzed this marker in patients undergoing HIPEC. CRC is the second leading cause of cancer-related death worldwide, mainly attributed to metastatic disease. Peritoneum is one of the most common metastatic sites and selected patients with peritoneal metastasis may undergo a curative-intent aggressive therapy based on CRS combined with HIPEC usually after neoadjuvant systemic chemotherapy. In the setting of a therapy not devoid of risk, proper patient selection is a crucially important aspect in optimizing outcomes but remains challenging.

To this end, within the personalized medicine framework, identifying novel prognostic biomarkers is essential and FRMD6 expression could be a marker of good prognosis in patients with peritoneal involvement.