Immunohistochemical Evaluation of Minichromosome Maintenance Protein 7 (MCM7), Topoisomerase IIα, and Ki-67 in Diffuse Malignant Peritoneal Mesothelioma Patients Using Tissue Microarray.

Abstract

Immunohistochemistry and tissue microarray (TMA) were used to perform a prognostic analysis of markers related to cell proliferation in diffuse malignant peritoneal mesothelioma (DMPM). Clinicopathologic data were extracted from a prospectively collected database containing cases of peritoneal mesothelioma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the National Cancer Institute of Milan from 1995 to 2013. Eighty-one DMPM patients were recruited and their tissue samples were used to construct TMAs. We evaluated the immunoexpressions of markers related to cell proliferation-topoisomerase IIα, minichromosome maintenance protein 7 (MCM7), and Ki-67-and then conducted a multivariate Cox model to identify the predictors of overall survival (OS) and progression-free survival (PFS) among the following parameters: age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, baseline serum albumin, Charlson Comorbidity Index, previous systemic chemotherapy, histological subtype (epithelioid vs. biphasic/sarcomatoid), peritoneal cancer index, completeness of cytoreduction (CC), and proliferative biological markers. The rates of high/intermediate immunoreactivity were 95 % for topoisomerase IIα and 90 % for MCM7, and the median Ki-67 labeling index was 5 %. The independent predictors of OS were baseline serum albumin >3.5 g/dl, CC, and Ki-67 >5 %, whereas those for PFS were an ECOG performance status of 0, baseline serum albumin >3.5 g/dl, Charlson Comorbidity Index >3, previous systemic chemotherapy, morbidity G3-5, and Ki-67 >5 %. The remaining biological markers were not associated with outcome. Ki-67 was found to be a new powerful determinant of outcome. Patients with a Ki-67 labeling index >5 % carry a very poor prognosis and do not benefit from the combined procedure. Further studies should be conducted to confirm the present data.