Xi Yun, Zhou Fang, Liu Yulan, Zhou Haifei, Lu Xiaoyan, Fang Xianhua, Yan Lifeng, Zhou Jianqing, Zhu Tao, Tang Huarong
Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, China.
Department of Gynecology, Zhejiang Hospital, Hangzhou, China.
Ther Adv Med Oncol. 2025 Jul 31;17:17588359251361880. doi: 10.1177/17588359251361880. eCollection 2025.
Gastric-type endocervical adenocarcinoma (GAS), the predominant non-human papillomavirus cervical cancer, is highly aggressive with poor prognosis. No drugs are effective against advanced or recurrent GAS.
This study aimed to analyze the clinical and pathological characteristics of GAS, evaluate the expression of targets for targeted drug therapy, and assess the predictive value of Immunoscore for prognosis.
The study retrospectively analyzed the clinical and pathological characteristics and follow-up data of 107 cases of GAS and 523 of human papillomavirus-associated cervical adenocarcinoma (HPVA) treated surgically at Zhejiang Cancer Hospital between January 2015 and December 2022.
Immunohistochemistry was used to detect the expressions of Tumor Protein 53 (P53), p16 protein (P16), Human Epidermal Growth Factor Receptor 2, Mucin 6, Programmed Death-Ligand 1 (PD-L1), Claudin 18.2, and immune markers Cluster of Differentiation 3/Cluster of Differentiation 8 in tumors. Ridge regression analysis was employed to obtain an Immunoscore, and receiver-operating characteristic curves were used to calculate the cutoff value to divide the Immunoscores into the low-risk and high-risk groups. The Kaplan-Meier method and Cox proportional hazards regression model were used in the survival and multivariate analyses, respectively.
Compared with HPVA, GAS was associated with later staging, larger tumor size, deeper invasion, and higher risks of lymph node metastasis, lymphovascular space invasion, parametrial involvement, ovarian metastasis, and peritoneal metastasis ( < 0.05). For patients in stages IA-IIIC2, the risk of recurrence/metastasis in GAS was significantly higher than that in HPVA (43.9% vs 21.2%, < 0.001). The 5-year rates of progression-free survival (PFS; 44% vs 75.4%, < 0.001) and overall survival (OS; 47.9% vs 82.5%, < 0.001) were significantly lower in GAS than in HPVA. In the multivariate analysis, the histological type of GAS was an independent risk factor for OS (hazard ratio (HR) = 1.773, = 0.023). In GAS, 71.7% and 46.7% were positive for Claudin 18.2 and PD-L1 (combined proportion score ⩾1), respectively. Four (3.7%) patients showed 3+ expression of Her-2. Cox multivariate analysis results indicated the Immunoscore as an independent predictive factor for PFS (HR = 2.532, = 0.002) and OS (HR = 3.147, = 0.003) in patients with GAS. The 5-year OS rates for the low- and high-risk groups based on the Immunoscore were 62.1% and 0% ( < 0.001), and the 5-year PFS rates were 57.3% and 9.0% ( < 0.001), respectively.
GAS is extremely aggressive and prone to recurrence and has a poor prognosis. The Immunoscore is an independent prognostic factor of GAS. Claudin 18.2 is expressed at high rates in GAS and is a potential therapeutic target.
胃型宫颈内膜腺癌（GAS）是主要的非人乳头瘤病毒型宫颈癌，侵袭性强，预后差。尚无药物对晚期或复发性GAS有效。
本研究旨在分析GAS的临床和病理特征，评估靶向药物治疗靶点的表达情况，并评估免疫评分对预后的预测价值。
本研究回顾性分析了2015年1月至2022年12月在浙江省肿瘤医院接受手术治疗的107例GAS患者和523例人乳头瘤病毒相关宫颈腺癌（HPVA）患者的临床和病理特征及随访数据。
采用免疫组织化学法检测肿瘤中肿瘤蛋白53（P53）、p16蛋白（P16）、人表皮生长因子受体2、黏蛋白6、程序性死亡配体1（PD-L1）、紧密连接蛋白18.2以及免疫标志物分化簇3/分化簇8的表达。采用岭回归分析获得免疫评分，并使用受试者工作特征曲线计算临界值，将免疫评分分为低风险组和高风险组。生存分析和多变量分析分别采用Kaplan-Meier法和Cox比例风险回归模型。
与HPVA相比，GAS与分期较晚、肿瘤体积较大、浸润较深以及淋巴结转移、脉管间隙浸润、宫旁组织受累、卵巢转移和腹膜转移风险较高相关（P<0.05）。对于IA-IIIC2期患者，GAS的复发/转移风险显著高于HPVA（43.9%对21.2%，P<0.001）。GAS的5年无进展生存率（PFS；44%对75.4%，P<0.001）和总生存率（OS；47.9%对82.5%，P<0.001）显著低于HPVA。多变量分析中，GAS的组织学类型是OS的独立危险因素（风险比（HR）=1.773，P=0.023）。在GAS中，紧密连接蛋白18.2和PD-L1（联合比例评分⩾1）的阳性率分别为71.7%和46.7%。4例（3.7%）患者Her-2呈3+表达。Cox多变量分析结果表明，免疫评分是GAS患者PFS（HR=2.532，P=0.002）和OS（HR=3.147，P=0.003）的独立预测因素。基于免疫评分的低风险组和高风险组的5年OS率分别为62.1%和0%（P<0.001），5年PFS率分别为57.3%和9.0%（P<0.001）。
GAS侵袭性极强，易于复发，预后较差。免疫评分是GAS的独立预后因素。紧密连接蛋白18.2在GAS中高表达，是潜在的治疗靶点。
