Abstract: Clinicopathological features, prognosis and effects of adjuvant chemotherapy of primary gastric adenosquamous carcinoma(PGASC): a multicenter retrospective study based on propensity score matching                ZHANG Zi-zhen*,  ZHANG Hao-yu, WANG Xin-xin, et al. *Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China 
Corresponding authors: CAO Hui, E-mail:caohuishcn@hotmail.com; CHEN Lin, E-mail: chenlinbj@vip.sina.com；LI Guo-xin, E-mail: gzliguoxin@163.com; HUANG Chang-ming, E-mail: hcmlr2002@163.com
ZHANG Zi-zhen, ZHANG Hao-yu, WANG Xin-xin, CHEN Hao, LIN Jian-xian, and Muerzhate Aimaiti are the first authors who contributed equally to the article
Abstract    Objective    To analyse and discuss the clinicopathological features, survival prognosis and chemotherapy efficacy of primary gastric adenosquamous carcinoma (PGASC). Methods    Clinicopathological data of 48 pathologically confirmed cases of PGASC from 5 gastric cancer centers in China from January 2014 to December 2019 (16 cases from Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 14 cases from Chinese People's Liberation Army General Hospital, 9 cases from Nanfang Hospital, Southern Medical University, 6 cases from Fujian Medical University Union Hospital, and 3 cases from The First People’s Hospital of Kashgar) were retrospectively collected and 487 pathologically confirmed cases of gastric adenocarcinoma (GAC) from Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2016 to December 2016 were collected as control group. Then 48 PGASC and 96 GAC were matched by propensity score matching (PSM) according to the ratio of 1∶2 for analysis. Kaplan-Meier method was used to draw the survival curve, and Log-rank test was used to compare the 3 and 5-year overall survival (OS) rates of the two groups and stratified analysis was carried out on the efficacy of locally advanced PGASC adjuvant chemotherapy. Results     Compared with GAC group, PGASC group showed that the proportion of primary cancer located in cardia  (39.6% vs.22.4%, P<0.01), presented locally advanced and IV stage (95.8% vs.78.6%, P＜0.01), invaded serosa (83.3% vs.65.7%, P<0.05), vessel (39.6% vs.10.5%, P<0.01) and nerve  (41.7% vs.12.7%, P<0.01) was higher. Immunohistochemical results showed that the proportion of Ki67>50% in PGASC group was significantly lower than that in GAC group (33.3% vs.63.4%, P<0.01), while the proportion of PD-L1 ≥10% in tumor microenvironment was significantly higher than that in GAC group (32.4% vs.2.9%, P<0.01). After PSM, the proportion of patients with PD-L1≥10% was still significantly higher than that of the GAC group and the prognostic analysis showed that the OS of PGASC patients was significantly worse than that of GAC patients(3 year’s OS, 30.7% vs.68.4%, P＜0.01; 5 year’s OS, 21.5% vs.64.2%, P＜0.01). Further analysis of the efficacy of postoperative adjuvant chemotherapy in locally advanced patients showed that the OS of patients who received postoperative adjuvant chemotherapy in GAC group was significantly better than that of those who did not receive chemotherapy(P<0.01). There were no statistical differences in OS between PGASC groups(P>0.05). Conclusion  PGASC is a rare pathological type of gastric cancer with unique locations, a high degree of malignancy, low sensitivity to traditional chemotherapy and often results in poor prognosis. Special histological characteristics, unique biological behaviors and changes in immune microenvironment was found in PGASC patients such as PD-L1, relevant basic research and clinical treatment methods need to be further explored. 

Key words: primary gastric adenosquamous carcinoma, gastric adenocarcinoma, prognosis, adjuvant chemotherapy

摘要： 目的    分析原发性胃腺鳞癌（PGASC）病人的临床病理特征、治疗效果及生存预后。方法    回顾性分析2014 年1月至2019年12月5家医院收治的48例PGASC病例的临床资料（PGASC组），包括上海交通大学医学院附属仁济医院16例，中国人民解放军总医院14例，南方医科大学南方医院9例，福建医科大学附属协和医院6例，喀什地区第一人民医院3例；另以2016年1—12月上海交通大学医学院附属仁济医院收治的487例胃腺癌（GAC）病人作为对照（GAC组）。通过倾向性评分匹配法（PSM）按1∶2匹配后，PGASC组48例，GAC组96例。应用Kaplan-Meier法绘制生存曲线，采用Log-rank检验比较两组3、5年总生存率（OS）并分层分析辅助化疗对局部进展期PGASC病人预后的影响。结果    相较于GAC组，PGASC组原发灶位于近贲门部位比例（39.6% vs. 22.4%）、就诊时病人局部进展期和晚期比例（95.8% vs. 78.6%）、浆膜侵犯比例（83.3% vs. 65.7%）、脉管侵犯比例（39.6% vs. 10.5%）以及神经侵犯比例（41.7% vs. 12.7%）均更高，且差异有统计学意义（均P<0.01）。PGASC组中Ki-67＞50%的比例显著低于GAC组（33.3% vs. 63.4%，P＜0.01），而肿瘤微环境中细胞程序性死亡配体1（PD-L1）≥10%的比例显著高于GAC组（32.4% vs. 2.9%，P＜0.01）。PSM后两组仅PD-L1表达存在差异，预后分析结果显示PGASC组OS劣于GAC组（3年OS：30.7% vs. 68.4%，P＜0.01；5年OS：21.5% vs. 64.2%，P＜0.01）。进一步分析局部进展期病人术后辅助化疗效果，GAC组中术后接受辅助化疗者OS显著优于未接受化疗者（P＜0.01），而PGASC组中术后是否接受辅助化疗对OS的影响无统计学意义（P＞0.05）。结论    PGASC是一种罕见的胃癌病理类型，其恶性程度较高，对传统化疗敏感性较低，病人预后较差。PGASC存在特殊的组织学特征、生物学行为及PD-L1表达模式，相关基础研究及临床治疗方法有待进一步深入探索。 

关键词: 原发性胃腺鳞癌, 临床病理特征, 预后, 辅助化疗