Zahan Umme Farzana, Sohel Hasibul Islam, Nakayama Kentaro, Ishikawa Masako, Nagase Mamiko, Razia Sultana, Kanno Kosuke, Yamashita Hitomi, Sonia Shahataj Begum, Kyo Satoru
Department of Obstetrics and Gynecology, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan.
Department of Obstetrics and Gynecology, East Medical Center, Nagoya City University, Nagoya 464-8547, Japan.
Int J Mol Sci. 2025 Aug 1;26(15):7469. doi: 10.3390/ijms26157469.
Gastric-type cervical adenocarcinoma (GCA) is a rare and aggressive subtype of cervical adenocarcinoma. Despite its clinical significance, its molecular carcinogenesis and therapeutic targets remain poorly understood. This study aimed to compare the clinicopathological, immunohistochemical, and molecular profiles of GCA and usual-type cervical adenocarcinoma (UCA), exploring prognostic and therapeutic biomarkers in a Japanese population. A total of 110 cervical adenocarcinoma cases, including 16 GCA and 94 UCA cases, were retrospectively analyzed for clinicopathological features, and a panel of immunohistochemical markers was assessed. Sanger sequences were performed for the , , and genes, and survival and clinicopathological correlations were assessed using Kaplan-Meier and Cox regression analyses. GCA was significantly associated with more aggressive features than UCA, including lymph node involvement, advanced FIGO stages, increasing recurrence rate, and poor survival status. High ARID1B expression was observed in a subset of GCA cases and correlated with worse progression-free and overall survival. Additionally, PD-L1 expression was more frequent in GCA than UCA and was associated with unfavorable prognostic factors. Conversely, UCA cases showed strong p16 expression, supporting their HPV-driven pathogenesis. Molecular profiling revealed and mutations in both subtypes, while mutations were identified exclusively in GCA. These findings reveal distinct clinical and molecular profiles for both tumor types and underscore ARID1B and PD-L1 as predictive prognostic and therapeutic biomarkers in GCA, implicating the use of subtype-specific treatment strategies.
胃型宫颈腺癌(GCA)是宫颈腺癌中一种罕见且侵袭性强的亚型。尽管其具有临床意义,但其分子致癌机制和治疗靶点仍知之甚少。本研究旨在比较GCA和普通型宫颈腺癌(UCA)的临床病理、免疫组化和分子特征,探索日本人群中的预后和治疗生物标志物。对110例宫颈腺癌病例(包括16例GCA和94例UCA)进行回顾性分析其临床病理特征,并评估一组免疫组化标志物。对 、 和 基因进行桑格测序,并使用Kaplan-Meier和Cox回归分析评估生存情况与临床病理的相关性。与UCA相比,GCA与更具侵袭性的特征显著相关,包括淋巴结受累、国际妇产科联盟(FIGO)分期较高、复发率增加和生存状况较差。在一部分GCA病例中观察到ARID1B高表达,且与无进展生存期和总生存期较差相关。此外,GCA中PD-L1表达比UCA更频繁,且与不良预后因素相关。相反,UCA病例显示出强烈的p16表达,支持其由人乳头瘤病毒(HPV)驱动的发病机制。分子谱分析显示两种亚型均存在 和 突变,而 突变仅在GCA中被鉴定出来。这些发现揭示了两种肿瘤类型不同的临床和分子特征,并强调ARID1B和PD-L1作为GCA中预测预后和治疗的生物标志物,提示使用亚型特异性治疗策略。
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