Overexpression of annexin A4 is associated with chemoresistance in papillary serous adenocarcinoma of the ovary
Overexpression of annexin A4 is associated with chemoresistance in papillary serous adenocarcinoma of the ovary
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DOI：
10.1016/j.humpath.2012.08.024
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发表时间：
2013-06-01
期刊：
影响因子：
3.3
通讯作者：
Kim, Byoung-Gie
中科院分区：
文献类型：
--
作者：
Choi, Chel Hun;Sung, Chang Ohk;Kim, Byoung-Gie
卵巢癌中的膜联蛋白 A4 研究主要集中在透明细胞癌，这种癌对化疗表现出很强的抵抗力。本研究的目的是检查浆液性卵巢癌中膜联蛋白 A4 的表达和细胞定位。我们通过实时聚合酶链反应评估了 40 例卵巢浆液性癌组织中膜联蛋白 A4 的表达。此外，通过免疫组织化学研究了 70 个上皮性卵巢癌组织中该蛋白在肿瘤内的分布。 14 个化疗耐药肿瘤中的膜联蛋白 A4 转录物水平高于 26 个化疗敏感肿瘤中的膜联蛋白 A4 转录物水平 (P = .013)。免疫组化表达显示，70份样本中有14份（20.0%）检测到核表达，70份样本中有17份（24.3%）检测到细胞质表达。结果显示，35.7% 有核表达的女性对铂类化疗耐药，而无核表达的女性中只有 14.3% 对化疗耐药 (P = .065)。此外，核染色患者的无病生存期明显短于染色阴性的患者。多变量比例风险模型显示，分期和核膜联蛋白 A4 表达是独立的预后因素（风险比分别为 6.34 [P = .001] 和 2.85 [P = .011]）。这项研究表明，膜联蛋白 A4 的过度表达和核定位与浆液性乳头状卵巢癌患者的化疗耐药性和较差的生存率有关。未来的研究需要开发针对卵巢上皮腺癌患者的膜联蛋白 A4 的新疗法。 (C) 2013 Elsevier Inc. 保留所有权利。
Annexin A4 study in ovarian cancer has been primarily focused on clear cell carcinoma, which exhibits strong resistance to chemotherapy. The aim of this study was to examine the expression and cellular localization of annexin A4 in serous ovarian carcinomas. We evaluated the expression of annexin A4 with real-time polymerase chain reaction in 40 ovarian serous carcinoma tissues. Furthermore, the distribution of the protein within the tumor was studied by immunohistochemistry in 70 epithelial ovarian carcinoma tissues. The levels of annexin A4 transcripts were higher in 14 chemoresistant tumors than those in 26 chemosensitive tumors (P = .013). Immunohistochemical expressions showed that nuclear expression was detected in 14 (20.0%) of 70 samples, and cytoplasmic expression was detected in 17 (24.3%) of 70 samples. The results showed that 35.7% of women with nuclear expression were resistant to platinum-based chemotherapy, whereas only 14.3% of women without expression were chemoresistant (P = .065). In addition, patients with nuclear staining had significantly shorter disease-free survival than did patients who showed negative staining. Multivariate proportional hazards model revealed that the stage and nuclear annexin A4 expression were independent prognostic factors (hazard ratios, 6.34 [P = .001] and 2.85 [P = .011], respectively). This study showed that overexpression and nuclear localization of annexin A4 are related to chemoresistance and poor survival in patients with serous papillary ovarian carcinomas. Future studies are required to develop new therapies targeting annexin A4 in patients with ovarian epithelial adenocarcinoma. (C) 2013 Elsevier Inc. All rights reserved.