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

被引:8
作者
Angelico, Giuseppe [1 ]
Ieni, Antonio [2 ]
Caltabiano, Rosario [3 ]
Santoro, Angela [1 ]
Inzani, Frediano [1 ]
Spadola, Saveria [1 ]
Tuccari, Giovanni [2 ]
Macri, Antonio [4 ,5 ]
Zannoni, Gian Franco [1 ,6 ]
机构
[1] Fdn Policlin Univ A Gemelli IRCCS, Dipartimento Sci Salute Donna Bambino & Sanita Pu, Unita Ginecopatol & Patol Mammaria, I-00168 Rome, Italy
[2] Univ Messina, Dept Human Pathol Adult & Dev Age Gaetano Barresi, Sect Pathol, I-98122 Messina, Italy
[3] Univ Catania, Sect Anat Pathol, Dept Gian Filippo Ingrassia, I-95123 Catania, Italy
[4] Univ Messina, Dept Human Pathol Adult & Dev Age Gaetano Barresi, Sect Surg & Peritoneal Surface Malignancy, I-98122 Messina, Italy
[5] Univ Messina, Soft Tissue Sarcoma Program, I-98122 Messina, Italy
[6] Univ Cattolica Sacro Cuore, Ist Anat Patol, I-00168 Rome, Italy
关键词
ovarian cancer; serous carcinoma; chemo-resistance; pathologic response; platinum-based chemotherapy; aquaporin; 1; beta-catenin; wingless-related integration site (wnt)/beta-catenin pathway; CHEMOTHERAPY RESPONSE SCORE; NEOADJUVANT CHEMOTHERAPY; PRIMARY SURGERY; CELL-MIGRATION; CANCER; AQUAPORIN-1; PROSTATE; DENSITY; LUNG;
D O I
10.3390/diagnostics11030452
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页数:11
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