metallothionein and Cystadenoma--Mucinous

Metallothioneins (MTs) are a family of cystein-rich metal-binding proteins, which are expressed in normal cells during fetal and postnatal life but also in a variety of human neoplasms. MT expression in human tumors has been linked to resistance to anticancer drugs and differentiation and progression in some types of tumors. This study examined the immunohistochemical expression of MTs in benign, borderline and malignant tumors of ovarian surface epithelium and the possible correlations with clinicopathological parameters and survival. A total of 87 cases with diagnosis of ovarian surface epithelial tumors were included. Specifically, 21 cases of benign cystadenomas (11 serous and 10 mucinous), 14 borderline (low malignant potential tumors, 8 mucinous and 6 serous) and 52 cases of ovarian cancer were analysed. Immunohistochemical expression of MT (cut-off level > 10% of tumor cells) was clearly associated with malignancy. A statistically significant correlation was found between the expression of MT in cancer cases and benign tumors (p < 0.0001) and cancer cases and borderline tumors p = 0.003. In cancer cases a difference was observed between grade I and III (p = 0.002). There was no correlation of MT overexpression with survival in the small number of ovarian carcinoma patients where it was analysed. MT constitutes a marker that characterizes aggressiveness and a high malignant potential in ovarian epithelial tumors. In diagnostic problems MT may help distinguish between benign, borderline and malignant tumors.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Cell Differentiation; Cell Proliferation; Cystadenoma, Mucinous; Cystadenoma, Serous; Diagnosis, Differential; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Metallothionein; Middle Aged; Ovarian Neoplasms; Tumor Suppressor Protein p53

Metallothioneins (MTs) are low molecular weight proteins that control cell proliferation via their metalloregulatory function. Several studies in various tumors have shown their influence in determining response to chemotherapy and prognosis. Because there has been no such study pertaining to ovarian tumors, we investigated MT expression and nuclear size in mucinous ovarian neoplasms (12 benign, 6 borderline, and 8 malignant). The percentage of MT-positive stained cells was significantly higher in the borderline than in the benign tumors, but lower than in the malignant tumors. Single layers of cells in the borderline tumors showed mild immunostaining in 50% of the cells and moderate staining in the remaining 50%, while 83.3% of cells within multilayered epithelium showed moderate to strong immunostaining. In the carcinomas, 87.5% of tumors showed moderate to strong staining in single-layered epithelium and moderate to strong staining of all the cells in multilayered epithelium. Morphometry measurements showed that the mean nuclear area of cells in the carcinomas was significantly larger than in the borderline or benign tumors. The nuclear area of cells in the carcinomas with early recurrence or metastasis was also significantly larger than in carcinomas without recurrence or metastasis. It is concluded that MT protein expression and nuclear size are possible markers for the evaluation of the progression of malignancy in mucinous ovarian tumors.

Topics: Cell Nucleus; Cystadenocarcinoma, Mucinous; Cystadenoma, Mucinous; Diagnosis, Differential; Female; Humans; Metallothionein; Ovarian Neoplasms; Predictive Value of Tests; Prognosis; Survival Rate