腹膜假黏液瘤155例病理预后因素分析

Pathological prognostic factors of pseudomyxoma peritonei

目的探讨腹膜假黏液瘤(pseudomyxoma peritonei,PMP)患者的病理学特征与预后的关系,寻找影响预后的独立病理指标。方法收集首都医科大学附属北京世纪坛医院2012至2018年手术的PMP病理标本,研究肿瘤的病理组织学类型、原发灶、淋巴结转移、脉管瘤栓、神经侵犯、细胞密度等病理组织学特征及黏蛋白、错配修复(MMR)基因相关蛋白、Ki-67、p53蛋白的免疫组织化学结果;收集临床治疗及随访资料,采用Kaplan-Meier法计算患者生存率;以生存预后模型进行单因素和多因素分析,研究独立影响PMP预后的病理学因素。结果共纳入155例PMP,男77例,女78例;中位年龄55岁(25~79岁);腹膜低级别黏液癌98例(63.2%),腹膜高级别黏液癌49例(31.6%),腹膜高级别黏液癌伴印戒细胞8例(5.2%)。淋巴结有转移者15例(9.7%),无转移者140例(90.3%);有脉管瘤栓者18例(11.6%),无脉管瘤栓者137例(88.4%);MMR蛋白缺失率6.3%(8/126);Ki-67阳性指数<50%者100例(64.5%),≥50%者55例(35.5%);p53野生型99例(63.9%),突变型56例(36.1%)。单因素分析发现影响患者生存的主要病理指标包括:性别、年龄、原发病灶、组织病理学类型、淋巴结转移、脉管瘤栓、神经侵犯、细胞密度、MMR蛋白缺失、Ki-67阳性指数、p53蛋白。多因素分析显示组织病理学类型(HR 59.78,P<0.01)、淋巴结转移(HR 3.74,P=0.028)、神经侵犯(HR 7.81,P=0.007)、MMR蛋白缺失(HR 9.82,P<0.01)为独立预后因子。结论组织病理学类型是PMP的最重要常规病理预后指标,MMR蛋白缺失是PMP的独立分子预后指标。

Objective To analyze the pathological features of pseudomyxoma peritonei (PMP) in correlation with the survival status and independent prognostic factors. Methods One-hundred and fifty-five PMP specimens were collected at Beijing Shijitan Hospital, Capital Medical University, from 2012 to 2018. Conventional histopathological evaluation was performed to document the primary tumor site, histopathological type, lymph nodes metastasis, tumor emboli in the blood and lymph vessels, nerve invasion and cellular density. The immunohistochemical parameters including Ki-67, p53, MMR-related protein, MUC2 and MUC5AC were analyzed. Clinical follow-up data were reviewed to correlate with pathological prognostic factors using Kaplan-Meier estimator and Cox proportional hazards regression model for univariate and multivariate analysis. Results Among 155 PMP patients, there were 77 males and 78 females. There were 98 cases (63.2%) of low-grade peritoneal mucinous carcinomatosis, 49 cases (31.6%) of high-grade peritoneal mucinous carcinomatosis, 8 cases (5.2%) of high-grade mucinous carcinoma peritonei with signet ring cells;only 15 cases (9.7%) with lymph node metastasis;18 cases (11.6%) with tumor emboli in the blood and lymph vessels;8/126 (6.3%) were positive dMMR;100 cases (64.5%) had Ki-67 label index <50%, and 56 cases(36.1%) presented with mutant type p53. Univariate analysis revealed 11 survival-related pathological parameters including gender, age, primary tumor site, histopathological type, lymph node metastasis, tumor emboli in the blood and lymph vessels, nerve invasion, cellular density, Ki-67 label index rate, p53 and dMMR. Multivariate analysis identified 4 independent prognostic factors including the histopathological type (HR 59.78, P<0.01), lymph node metastasis (HR 3.74, P=0.028), nerve invasion (HR 7.81, P=0.007) and dMMR (HR 9.82, P<0.01). Conclusions Histopathological type is the most important prognostic factor of PMP with dMMR as an independent molecular prognostic indicator.