Expression of Major Vault Protein in ovarian carcinoma

Abstract

Introduction: The major vault protein (MVP) is a component of large ribonucleoprotein complexes called Vaults. Vaults are organelles in eukaryotic cells, three times bigger than the ribosomes, associated with the nuclear pores. Their function has not been fully elucidated. Vaults are probably involved in RNA trafficking and cell signaling by regulating the selective permeability of the nuclear pores. Since Scheffer et al. showed that MVP is identical to the LRP (Lung Resistance Protein), a new role for the vaults emerged - a multi-drug resistance in malignant tumors. Objective: To evaluate the expression of MVP in advanced high-grade ovarian carcinoma and analyze possible correlations to the disease course and chemotherapy response. Material and methods: We tested the expression of MVP in 31 cases with ovarian cancer treated with the same postoperative chemotherapeutic protocol, 17 of which had a satisfactory response to the therapy (group I) and 14 had a poor response (group II). MVP expression was tested with immunostaining using the LRP-56 primary antibody and En-Vision Flex (DAKO) visualization kit and in two of the positive samples, electron microscopy was performed to confirm the localization of vaults at the nuclear pores and correlate the immunostaining pattern. Results: We found MVP over-expression in 50-100% of the tumor cell population in the second group, compared to cases with negative staining and cases with MVP staining in less than 30% of tumor cells in samples from the first group (p<0,01). Anti-MVP staining prior to chemotherapy could be a beneficial prognostic marker in cases with ovarian carcinoma, especially having in mind that its visualization (detection) exploits routine methodology. Conclusion: We found MVP expression in more than 50% of tumor cells in advanced highgrade ovarian carcinoma in 38.7% of cases. This overexpression is correlated to worse chemotherapy (platinum-based and taxanes) response and shorter event-free time.