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Tumor Budding and PDC Grade Are Stage Independent Predictors of Clinical Outcome in Mismatch Repair Deficient Colorectal Cancer

发布日期:2018/9/16 16:15:59 文章来源: 作者: 点击次数:1787

 

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Am J Surg Pathol 2018;42:60–68

Tumor Budding and PDC Grade Are Stage Independent Predictors of Clinical Outcome in Mismatch Repair Deficient Colorectal Cancer

Éanna Ryan,MB BCh,*† Yi Ling Khaw,MB,‡ Ben Creavin,MB BCh,*† Robert Geraghty,MSc,‡ Elizabeth J. Ryan, PhD,§ David Gibbons, MB, FCAP,‡ Ann Hanly, MD, FRCSI,*† Sean T. Martin, MD, FRCSI,*† P. Ronan O’Connell, MD, FRCSI, FRCS,*†§ Desmond C. Winter,MD, FRCSI,*† and Kieran Sheahan,MB, BSc, FRCPI, FRCPath, FCAP†‡§

Abstract: Mismatch repair deficient (dMMR) colorectal cancer (CRC) despite its association with poor histologic grade often has improved prognosis compared with MMR proficient CRC. Tumor budding and poorly differentiated clusters (PDCs) may predict metastatic potential of colorectal adenocarcinoma (CRC). In addition, their assessment may be more reproducible than the evaluation of other histopathologic parameters. Therefore, we wished to determine their potential as prognostic indicators in a cohort of dMMR CRC patients relative to histologic grade. We investigated the predictive value of conventional WHO grade, budding, PDC grade and other histopathologic parameters on the presence of lymph node metastasis (LNM) and clinical outcome in 238 dMMR CRCs. MMR status was determined by immunohistochemistry for the mismatch repair proteins hMLH1, hMSH2, hMSH6, and hPMS2. Tumor budding and PDCs were highly correlated (r=0.701; P<0.000). Both budding and PDC grade were associated with WHO grade, perineural invasion, lympho-vascular invasion, and extramural vascular invasion, and the presence of LNM in dMMR CRC (P<0.009). Independent predictors of LNM were PDC grade (odds ratio, 4.12; 95% confidence interval [CI], 1.69-10.04; P=0.011) and EMVI (odds ratio, 3.81; 95% CI, 1.56-9.19; P<0.000). Only pTstage (hazard ratio [HR], 4.11; 95% CI, 1.48-11.36; P=0.007) and tumor budding (HR, 2.99; 95% CI, 1.72-5.19; P<0.000) were independently associated with worse disease-free survival (DFS). If tumor budding was excluded from the model, PDC grade became significant for DFS (HR, 2.34; 95% CI, 1.34-4.09; P=0.003). WHO Grade does not independently correlate with clinical outcome in dMMR CRC. PDC grade and extramural vascular invasion are independent predictors of LNM. Tumor budding and pTstage are the best predictors of DFS. If tumor budding cannot be assessed, PDC grade may be used as a prognostic surrogate.

 

在错配修复缺陷的结直肠癌中肿瘤出芽和PDC分级是临床结局的独立预测因素

摘要:错配修复缺陷(dMMR)的结直肠癌(CRC)尽管与组织学分级差有关,但与MMR正常的CRC相比通常预后较好。肿瘤出芽和低分化细胞簇(PDC)可以预测结直肠腺癌(CRC)的转移潜能。此外,这两者的评估可能比其他组织病理学参数更有可重复性。因此,我们希望通过一组dMMR CRC患者的组织学分级来确定其作为预后因素的潜能。本文基于淋巴结转移(LNM)和的临床结局研究了238dMMR结直肠癌的传统WHO分级、肿瘤出芽、PDC分级及其他组织病理学参数的预测价值,免疫组化检测MMR状态:错配修复蛋白hMLH1hMSH2hMSH6hPMS2。肿瘤出芽与PDCs高度相关(r = 0.701p0)。在dMMR CRC中肿瘤出芽和PDC分级都与WHO分级、神经侵犯、淋巴血管侵犯、肠壁外血管侵犯(EMVI)及淋巴结转移相关(p0.009)。淋巴结转移的独立预测因子是PDC分级(比值比,4.1295%置信区间[CI]1.69-10.04; P=0.011) EMVI (比值比, 3.8195% CI1.56-9.19P<0.000)。只有pT分期(风险比[HR]4.1195% CI1.48-11.36P = 0.007)和肿瘤出芽(HR2.9995% CI1.72-5.19P0)是独立的,与较差的无病生存期(DFS)相关。除外肿瘤出芽,PDC分级对于DFS有更重要意义(HR2.3495% CI1.34-4.09P = 0.003)。在dMMR CRCWHO分级与临床预后不完全相关。PDC分级和肠壁外血管侵犯是淋巴结转移的独立预测因素。肿瘤出芽和pT分期是DFS的最佳预测因素。如果不能对肿瘤出芽进行评估,PDC分级可作为预后替代。(翻译 杨巧)

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