Gao Shangshu, Song Yan
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Diagn Pathol. 2025 Jun 10;20(1):73. doi: 10.1186/s13000-025-01666-7.
To investigate the clinicopathological and molecular features, diagnosis, and differential diagnosis of gastric-type cervical adenocarcinoma (GAS).
A retrospective analysis was conducted on 100 patients diagnosed with GAS at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, from January 2017 to January 2025. Clinicopathological data, histological characteristics, and immunohistochemical expression patterns were analyzed. Targeted next-generation sequencing (NGS) was performed on 11 cases.
The cohort comprised 100 GAS patients (median age 50 years). Common clinical manifestations included abnormal uterine bleeding and vaginal discharge, with a significant proportion presenting at advanced FIGO stages (II-IV). Histological features were characteristic, and immunohistochemistry, including markers like MUC6, p16, PAX8, and PAX2, was crucial for diagnosis and differential diagnosis. Molecular analysis of 11 cases revealed a distinct high-frequency somatic mutation profile, including TP53 (72.7%), KRAS (45.5%), SMAD4 (45.5%), CDKN2A (36.4%), PIK3CA (27.3%) and STK11 (18.2%). This profile showed molecular homology with pancreaticobiliary adenocarcinoma and was characterized by microsatellite stable (MSS) and low tumor mutational burden (TMB). Regarding molecular markers and prognosis, aberrant p53 expression was frequent (50%, 37/74) but showed no significant association with clinicopathological factors or survival outcomes (p > 0.05). In contrast, PD-L1 expression (CPS ≥ 1) was significantly associated with higher FIGO stage (p = 0.021) and shorter progression-free survival (PFS) (p = 0.046).
GAS is a highly malignant, HPV-independent cervical adenocarcinoma characterized by atypical clinical symptoms and complex histology. This study, representing a large cohort from Northern China, provides comprehensive insights into its clinicopathological and molecular landscape. We characterized its unique molecular profile and, importantly, identified PD-L1 (CPS ≥ 1) as a potential prognostic marker associated with shorter PFS. These findings contribute to improving diagnosis, understanding biological behavior, and identifying potential therapeutic targets for this aggressive subtype.
探讨胃型宫颈腺癌（GAS）的临床病理及分子特征、诊断及鉴别诊断。
对2017年1月至2025年1月在中国医学科学院肿瘤医院/国家癌症中心/国家癌症临床研究中心确诊为GAS的100例患者进行回顾性分析。分析临床病理数据、组织学特征及免疫组化表达模式。对11例患者进行靶向二代测序（NGS）。
该队列包括100例GAS患者（中位年龄50岁）。常见临床表现为子宫异常出血和阴道分泌物增多，相当一部分患者在国际妇产科联盟（FIGO）晚期（II-IV期）就诊。组织学特征具有特异性，免疫组化，包括MUC6、p16、PAX8和PAX2等标志物，对诊断和鉴别诊断至关重要。对11例患者的分子分析显示出独特的高频体细胞突变谱，包括TP53（72.7%）、KRAS（45.5%）、SMAD4（45.5%）、CDKN2A（36.4%）、PIK3CA（27.3%）和STK11（18.2%）。该谱与胰胆管腺癌显示分子同源性，特征为微卫星稳定（MSS）和低肿瘤突变负荷（TMB）。关于分子标志物与预后，p53异常表达常见（50%，37/74），但与临床病理因素或生存结局无显著相关性（p>0.05）。相比之下，程序性死亡受体配体1（PD-L1）表达（综合阳性评分[CPS]≥1）与更高的FIGO分期显著相关（p=0.021），无进展生存期（PFS）更短（p=0.046）。
GAS是一种高度恶性、人乳头瘤病毒（HPV）非依赖性宫颈腺癌，具有非典型临床症状和复杂组织学特征。本研究代表了来自中国北方的一个大型队列，全面深入地揭示了其临床病理和分子特征。我们明确了其独特的分子谱，重要的是，确定PD-L1（CPS≥1）为与较短PFS相关的潜在预后标志物。这些发现有助于改善诊断、理解生物学行为并确定这种侵袭性亚型的潜在治疗靶点。
