Cytoplasmic expression of laminin-5γ2 chain is associated with progression and acquisition of malignant traits in ovarian serous and mucinous tumors

Abstract

Ovarian tumors are classified into adenoma, borderline tumor, and adenocarcinoma based on cellular atypia and invasion. However, invasion can be difficult to assess histologically, underscoring the need for objective biomarkers. Laminin-5γ2 chain (Lam5γ2), a component of the basement membrane, has been implicated in tumor cell invasion in various malignancies. This study aimed to investigate the immunohistochemical expression of Lam5γ2 as a potential adjunctive biomarker associated with invasive phenotypes in ovarian serous and mucinous tumors. Lam5γ2 immunohistochemistry was performed on 80 ovarian tumor specimens, including adenomas, borderline tumors, and adenocarcinomas of serous and mucinous subtypes. Lam5γ2 expression patterns were compared across histological categories. In serous tumors, Lam5γ2 expression along the basement membrane was preserved in approximately half of adenomas and borderline tumors but was absent in all adenocarcinomas. Notably, cytoplasmic expression was observed in 11 of 12 serous adenocarcinomas (92%), and cytoplasmic staining was more frequent in borderline tumors and adenocarcinomas than in adenomas. A similar pattern was observed in mucinous tumors, with a decrease in basement membrane expression from adenomas to borderline tumors to adenocarcinomas. In mucinous adenocarcinomas, cytoplasmic expression was present in 6 of 10 cases, while basement membrane linear expression was retained in 3 of 10 cases. These differences were statistically significant in both serous and mucinous tumors (P <.001 and P = .03, respectively). Loss of Lam5γ2 expression from the basement membrane and aberrant cytoplasmic localization in ovarian serous and mucinous tumor cells were associated with histological progression and invasive phenotypes. Thus, Lam5γ2 immunoreactivity may serve as a potential adjunctive biomarker, particularly in diagnostically challenging borderline or microinvasive cases, pending validation in larger, independent cohorts.

Keywords: basement membrane; cytoplasmic expression; laminin-5γ2; malignant transformation; mucinous tumor; ovarian cancer; serous tumor.