Combined phospho-Akt and PTEN expressions associated with post-treatment hysterectomy after conservative progestin therapy in complex atypical hyperplasia and stage Ia, G1 adenocarcinoma of the endometrium
Combined phospho-Akt and PTEN expressions associated with post-treatment hysterectomy after conservative progestin therapy in complex atypical hyperplasia and stage Ia, G1 adenocarcinoma of the endometrium
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DOI：
10.1016/j.canlet.2006.06.013
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发表时间：
2007-04-08
期刊：
影响因子：
9.7
通讯作者：
Taketani, Yuji
中科院分区：
文献类型：
--
作者：
Minaguchi, Takeo;Nakagawa, Shunsuke;Taketani, Yuji
复杂性不典型增生(CAH)或Ia、G1期子宫内膜腺癌(IaG1期)的年轻患者，如欲保留生育能力，可选择口服孕激素、醋甲羟孕酮(MPA)保守治疗。然而，保守治疗存在进展和复发的潜在风险。为了寻找甲孕酮敏感性的分子标志物，我们对31例甲孕酮治疗的CAH或IaG1患者进行了PTEN、磷酸化Akt、P53、ER和PGR的免疫组织化学检测。12例CAH患者中11例(92%)和19例IaG1患者中15例(79%)初步完全缓解，5例患者因无反应而行子宫切除术。患有CAH的I-I应答患者中有4人(36%)和15名IaG1应答患者中的5人(33%)后来复发。9名CAH患者中有5名(56%)和11名JaG1患者中有3名(27%)在不孕治疗后怀孕。免疫组织化学分析显示，甲孕酮能显著降低磷酸化Akt的表达(p=0.002)。此外，弱Phosho-Akt或PTEN-空表达这两个因素的组合被发现与接受子宫切除术显著相关(p=0.04)，但每个因素都显示出无统计学意义的趋势(p分别为0.07和0.2)。在对甲孕酮完全有效的不孕症治疗后，ER和PGR的强表达与成功妊娠显著相关(p=0.02)。我们在体内的观察表明，甲孕酮的抗肿瘤作用可能是通过Akt的去磷酸化来实现的，免疫组织化学检测Akt和PTEN的表达可能能够预测甲孕酮治疗的结果。(C)2006爱思唯尔爱尔兰有限公司。保留所有权利。
Young patients with complex atypical hyperplasia (CAH) or stage Ia, G1 adenocarcinoma (IaG1) of the endometrium, who desire to preserve fertility, can select the conservative therapy by oral progestin, medroxyprogesterone acetate (MPA). However, conservative treatments involve potential risks of progression and recurrence. In an attempt to find out molecular markers for sensitivity to MPA, we performed immunohistochemical analysis of PTEN, phospho-Akt, p53, ER and PgR in MPA-treated 31 cases with CAH or IaG1. Eleven of 12 cases (92%) with CAH and 15 of 19 cases (79%) with IaG1 demonstrated an initial complete response, while five patients underwent hysterectomy due to no response. Four of I I responders (36%) with CAH and five of 15 responders (33%) with IaG1 later developed relapse. Five of nine patients (56%) with CAH and three of 11 patients (27%) with JaG1 became pregnant after infertility treatment. Immunohistochemical analysis revealed that phospho-Akt expression was significantly decreased by MPA administration (p = 0.002). Furthermore, combination of two factors, weak phosho-Akt or PTEN-null expression, was found to be significantly associated with receiving hysterectomy (p = 0.04), while each factor showed a trend without statistical significance (p = 0.07 and 0.2, respectively). Strong expression of both ER and PgR significantly correlated with successful pregnancy after infertility treatment following complete response to MPA (p = 0.02). Our observations in vivo suggest that anti-tumor action of MPA may be mediated by dephosphorylation of Akt, and that immunohistochemical evaluation of phospho-Akt and PTEN may be able to predict the outcome of MPA therapy. (c) 2006 Elsevier Ireland Ltd. All rights reserved.