不同分期结直肠癌间质病理特征与预后及淋巴结转移的相关性

Correlations of stromal characteristics with prognosis and lymphatic metastasis of colorectal cancer patients at different stages

目的:探讨不同分期结直肠癌间质病理特征与淋巴结转移的相关性,以及其在预后评价中的价值。方法:回顾性分析2014-2017年贵州医科大学附属医院收治的148例,经内镜或外科手术切除、不同分期直结肠癌患者的临床和病理学特征。组织标本经HE染色后观察结直肠癌间质特征,包括肿瘤-间质比(tumor-stromal ratio,TSR)、肿瘤出芽(tumor budding,TB)、肿瘤浸润前端癌相关性成纤维(cancer associated fibroblasts,CAFs)细胞形态、以及肿瘤腺体富集区域癌性间质反应(desmoplastic reaction,DR)程度。Kaplan-Meire法绘制生存曲线;相关指标经Log-rank检验后,选取有统计学意义的因素纳入COX比例风险回归模型分析预后相关风险因素;单因素Logistics回归分析后选取有统计学意义的指标纳入多因素Logistics回归分析判断与淋巴结转移相关的风险因素。结果:148例患者的平均总生存时间为(43.66±20.13)个月(范围:1~67个月),中位总生存期为48.50个月。Log-rank检验显示,淋巴结转移、肿瘤浸润深度、肿瘤分化、TSR和TB的不同组间患者预后差异有统计学意义(P值均<0.05)。COX比例风险回归模型显示,淋巴结转移(P<0.001)、TSR(P<0.05)和TB(P<0.05)是影响预后的危险因素。相较于有淋巴结转移组(86例),无淋巴结转移组(62例)的TSR、TB及肿瘤浸润前端CAFs形态差异均有明显的统计学意义(P<0.001,P<0.05和P<0.05)。相较于TSR<1组(44例),TSR≥1组(114例)的TB、肿瘤分化程度、有无淋巴结转移及肿瘤浸润深度,差异均有明显的统计学意义(P值均<0.001)。多因素Logistics回归分析显示,肿瘤分化和TSR是影响淋巴结转移的危险因素。结论:本研究验证了主要的间质病理学特征与结直肠癌预后及淋巴结转移的相关性,其中TSR有望成为判断结直肠癌预后及淋巴结转移风险的指标。

Objective:To explore the correlation of pathological characteristics of tumor stoma with the lymph node metastasis of colorectal cancer patients at different stages,and the significance of these characteristics in prognosis evaluation.Methods:Pathological specimens endoscopically resected or surgically excised from 148 colorectal cancer patients at different stages treated in the Affiliated Hospital of Guizhou Medical University from 2014 to 2017 were retrospectively analyzed.The clinico-pathological characteristics of these specimens were collected.After hematoxylin-eosin(HE)staining,these specimens were observed to reveal stromal characteristics,including the tumor-stromal ratio(TSR),tumor budding(TB),cancer associated fibroblasts(CAFs)morphologies at the tumor-infiltrating front,and desmoplastic reaction(DR)degree in the enrichment area of neoplastic glands.The Kaplan-Meire method was used to draw the survival curve.Relevant indicators were checked through Log-rank test and the factors with statistical significance were included in the COX proportional hazard regression model to analyze prognostic risk factors.Indicators statistically significant in the single-factor Logistics regression analysis were included in the multi-factor Logistics regression analysis to determine risk factors associated with lymph node metastasis.Results:The average overall survival(OS)of the 148 patients was(43.66±20.13)months(range:1-67 months,median OS 48.50 months).The Log-rank test showed that patients in different groups exhibited differences in lymph node metastasis,tumor-infiltration depth,tumor differentiation,TSR,and TB(all P<0.05).The COX proportional hazard regression model revealed that lymph node metastasis(P<0.001),TSR(P<0.05),and TB(P<0.05)were prognostic risk factors.The group with no lymph node metastasis had significant differences with the group with lymph node metastasis in the TSR(P<0.001),TB(P<0.05),and CAFs morphologies at the tumor-infiltrating front(P<0.05).The TB,tumor differentiation,with or without lymph node metastasis,and tumor-infiltration depth of the TSR≥1 group displayed significant differences from those of the TSR<1 group.It was found from the multi-factor Logistics regression analysis that tumor differentiation(P<0.001)and TSR(P<0.001)were risk factors influencing lymph node metastasis.Conclusion:The correlations of the main pathological characteristics of tumor stroma with the prognosis and lymph node metastasis of colorectal cancer patients were studied.The TSR is expected to become an indicator for the prognosis and the risk of lymph node metastasis of colorectal cancer.