Abstract
Background. Mutations of the β-catenin gene (CTNNB1), leading to aberrant immunohistochemical expression of β-catenin, represent a key mechanism of WNT/β-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 β-catenin and AQP1 in ovarian carcinoma. Methods. We evaluated the expression of β-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 β-catenin staining pattern. The remaining 16 cases showed a preserved β-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 β-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.
Highlights
Epithelial ovarian carcinomas (OC) represent the most lethal gynaecological malignancy, being the fifth cause of female related cancer death [1]; its incidence and mortality are constantly increasing, mainly because the majority of women are diagnosed in advanced stage [1]
A cohort of 32 patients presenting with peritoneal carcinosis documented by diagnostic peritoneal biopsies which confirmed the histological diagnosis of high grade serous ovarian carcinoma (HGSC) was included in the study
All patients met the following additional inclusion criteria: International Federation of Gynecology and Obstetrics (FIGO) stage IIIC/IV, platinum-based NACT, and complete clinical response after neoadjuvant chemotherapy: score 0 according to the surgical scoring system for the IDS residual disease (0, no residual disease; 1, ≤1 cm residual disease; 2, >1 cm residual disease; 3, Unknown)
Summary
Epithelial ovarian carcinomas (OC) represent the most lethal gynaecological malignancy, being the fifth cause of female related cancer death [1]; its incidence and mortality are constantly increasing, mainly because the majority of women are diagnosed in advanced stage [1]. NACT and IDS have been proposed ever more for OC patients to increase the radicality of surgery and to reduce morbidity and mortality, taking into consideration the favorable results obtained in two randomized controlled phase III trials [3,4] It is well known the histopathological assessment of NACT response in OC represents the most important prognostic tool to establish the rate of complete citoreductive surgery and to predict patient outcome [5,6,7]. New prognostic biomarkers are needed to predict the biologic behavior and therapeutic response, improving the clinical outcomes of OC patients In this field, some previous studies highlighted the potential role in carcinogenesis, tumor progression and metastasis development of different cancers by Aquaporin 1 (AQP1), a small trans-membrane water channel protein [14,15,16,17,18,19]. AQP+ cases may represent a subset of poor responders who could be considered more eligible for cytoreductive surgery rather than for neoadjuvant chemotherapy
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