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.
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.
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DOI：
10.3390/diagnostics11030452
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发表时间：
2021-03-05
期刊：
影响因子：
--
通讯作者：
Zannoni GF
中科院分区：
文献类型：
--
作者：
Angelico G;Ieni A;Caltabiano R;Santoro A;Inzani F;Spadola S;Tuccari G;Macrì A;Zannoni GF
背景。 β-连环蛋白基因 (CTNNB1) 突变导致 β-连环蛋白免疫组织化学表达异常，这是卵巢癌中 WNT/β-连环蛋白通路改变的关键机制。水通道蛋白 1 (AQP1) 作为跨膜水通道家族蛋白的组成部分，已在不同的人类肿瘤中得到记录，最近在卵巢癌中也有记录。只有少数研究探讨了 β-catenin 和 AQP1 在卵巢癌中的发病机制和预后作用。方法。我们评估了 32 例腹膜癌患者术前腹膜活检中 β-catenin 和 AQP1 的表达，其中组织学诊断为高级别浆液性卵巢癌。此外，我们还研究了它们与网膜部位评估的化疗反应以及临床病理参数的潜在关联。结果。 16 例显示异常的膜和细胞质 β-连环蛋白染色模式。其余 16 例仅在细胞膜上保留了 β-catenin 表达； 20例膜染色阳性（AQP1+），12例膜染色阴性（AQP1-）。在 AQP+ 组中，我们在网膜组织完全缓解评分 (CRS) 1-2 中检测到 AQP1 表达与不良化疗反应显着相关，而在所有阳性病例中从未观察到 CRS 3。结论。我们的研究结果表明，β-连环蛋白和 AQP1 在卵巢肿瘤的一个亚组中表达，并在癌发生中发挥重要作用。受高级别浆液性癌影响的患者可分为两个不同的预测组：AQP+ 和 AQP-。 AQP+病例可能代表反应不佳者的一个子集，他们可能被认为更有资格接受细胞减灭术而不是新辅助化疗。
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.
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