P16 loss and mitotic activity predict poor survival in patients with peritoneal malignant mesothelioma

Purpose: Peritoneal malignant mesothelioma is an aggressive neoplasm for which intensive therapy improves survival in a subset of patients. We hypothesized that pathologic variables would stratify patients into favorable and unfavorable survival subgroups. Experimental Design: Fifty-four patients with peritoneal malignant mesothelioma were evaluated for trimodal therapy from 1995 to 2003. Two pathologists evaluated pathologic variables independently, and p16 status was analyzed by immunohistochemistry. Results: Patients not receiving trimodal therapy had a significantly increased risk of death [hazard ratio (HR), 9.6; 4.3-21.6; P < 0.0001]. Biphasic histology was also associated with increased risk of death (HR, 8.5; 3.4-21.8; P < 0.0001). In multivariate analysis adjusting for treatment modality and histologic type, high mitotic rate and p16 loss were associated with increased risk of death (HR, 3.074; 1.05-9.0; P < 0.04 and HR, 3.65; 1.3-10.2; P < 0.014, respectively). Conclusions: Biphasic histology, increased mitotic rate, and p16 loss were independently associated with poorer survival in peritoneal malignant mesothelioma. Among the trimodal treated patients, increased mitotic rate was associated with increased risk of death.