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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

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.
Lingua originaleEnglish
pagine (da-a)452-462
Numero di pagine11
RivistaDiagnostics
Volume11
DOI
Stato di pubblicazionePubblicato - 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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