Evaluation of Beta-Catenin Subcellular Localization and Water Channel Protein AQP1 Expression as Predictive Markers of Chemo-Resistance in Ovarian High-Grade Serous Carcinoma: Comparative Study between Preoperative Peritoneal Biopsies and Surgical Samples

Gian Franco Zannoni, Frediano Inzani, Giuseppe Angelico, Antonio Ieni, Rosario Caltabiano, Angela Santoro, Saveria Spadola, Giovanni Tuccari, Antonio Macrì

Research output: Contribution to journalArticle

Abstract

Background. Mutations of the beta-catenin gene (CTNNB1), leading to aberrant immunohistochemical expression of beta-catenin, represent a key mechanism of WNT/beta-catenin pathway alteration in ovarian cancer. Aquaporin 1 (AQP1), as component of transmembrane-water-channel family proteins, has been documented in different human tumors and, recently, also in ovarian carcinoma. Only few studies have investigated the pathogenetic and prognostic role of beta-catenin and AQP1 in ovarian carcinoma. Methods. We evaluated the expression of beta-catenin and AQP1 in the preoperative peritoneal biopsies of 32 patients with peritoneal carcinosis, in which a histological diagnosis of high grade serous ovarian carcinoma was made. Furthermore, we have investigated their potential association with chemotherapeutic response evaluated at the omental site, as well as with clinico-pathological parameters. Results. Sixteen cases showed an aberrant membranous and cytoplasmic beta-catenin staining pattern. The remaining 16 cases showed a preserved beta-catenin expression localized only in cell membranes; 20 cases showed positive membranous staining (AQP1+), while 12 cases were considered negative (AQP1-). In the AQP+ group, we detected a significant association of AQP1 expression with poor chemotherapy response in omental tissues complete response score (CRS) 1-2, while a CRS 3 was never observed in all positive cases. Conclusions. Our findings suggest that beta-catenin and AQP1 are expressed in a sub-group of ovarian tumors and play important roles in carcinogenesis. Patients affected by high grade serous carcinoma could be categorized in two different predictive groups: as AQP+ and AQP-. AQP+ cases may represent a subset of poor responders who could be considered more eligible for cytoreductive surgery rather than for neoadjuvant chemotherapy.
Original languageEnglish
Pages (from-to)452-462
Number of pages11
JournalDiagnostics
Volume11
DOIs
Publication statusPublished - 2021

Keywords

  • aquaporin 1
  • chemo-resistance
  • ovarian cancer
  • pathologic response
  • platinum-based chemotherapy
  • serous carcinoma
  • wingless-related integration site (wnt)/β-catenin pathway
  • β-catenin

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