Koelzer Viktor H, Assarzadegan Naziheh, Dawson Heather, Mitrovic Bojana, Grin Andrea, Messenger David E, Kirsch Richard, Riddell Robert H, Lugli Alessandro, Zlobec Inti
Institute of PathologyUniversity of BernBernSwitzerland.
Department of Pathology, Immunology and Laboratory Medicine, College of MedicineUniversity of FloridaGainesvilleFLUSA.
J Pathol Clin Res. 2017 Jul 26;3(3):171-178. doi: 10.1002/cjp2.73. eCollection 2017 Jul.
Tumour budding in colorectal cancer is an important prognostic factor. A recent consensus conference elaborated recommendations and key issues for future studies, among those the use of pan-cytokeratin stains, especially in stage II patients. We report the first prospective diagnostic experience using pan-cytokeratin for tumour budding assessment. Moreover, we evaluate tumour budding using pan-cytokeratin stains and disease-free survival (DFS) in stage II patients. To this end, tumour budding on pan-cytokeratin-stained sections was evaluated by counting the number of tumour buds in 10 high-power fields (0.238 mm), then categorizing counts as low/high-grade at a cut-off of 10 buds, in two cohorts. Cohort 1: prospective setting with 236 unselected primary resected colorectal cancers analysed by 17 pathologists during diagnostic routine. Cohort 2: retrospective cohort of 150 stage II patients with information on DFS. In prospective analysis of cohort 1, tumour budding counts correlated with advanced pT, lymph node metastasis, lymphovascular invasion, perineural invasion (all < 0.0001), and distant metastasis ( = 0.0128). In cohort 2, tumour budding was an independent predictor of worse DFS using counts [ = 0.037, HR (95% CI): 1.007 (1.0-1.014)] and the low-grade/high-grade scoring approach [ = 0.02; HR (95% CI): 3.04 (1.2-7.77), 90.7 versus 73%, respectively]. In conclusion, tumour budding assessed on pan-cytokeratin slides is feasible in a large pathology institute and leads to expected associations with clinicopathological features. Additionally, it is an independent predictor of poor prognosis in stage II patients and should be considered for risk stratification in future clinical studies.
结直肠癌中的肿瘤芽生是一个重要的预后因素。最近的一次共识会议阐述了未来研究的建议和关键问题，其中包括使用全细胞角蛋白染色，特别是在II期患者中。我们报告了首次使用全细胞角蛋白进行肿瘤芽生评估的前瞻性诊断经验。此外，我们在II期患者中使用全细胞角蛋白染色评估肿瘤芽生和无病生存期（DFS）。为此，通过在两个队列中计数10个高倍视野（0.238平方毫米）中的肿瘤芽数量，然后以10个芽为界将计数分为低/高级别，来评估全细胞角蛋白染色切片上的肿瘤芽生。队列1：前瞻性研究，17名病理学家在诊断常规过程中分析了236例未经选择的原发性切除结直肠癌。队列2：150例有DFS信息的II期患者的回顾性队列。在队列1的前瞻性分析中，肿瘤芽生计数与进展期pT、淋巴结转移、淋巴管浸润、神经周围浸润（均<0.0001）和远处转移（=0.0128）相关。在队列2中，使用计数法[=0.037，HR（95%CI）：1.007（1.0 - 1.014）]和低级别/高级别评分法[=0.02；HR（95%CI）：3.04（1.2 - 7.77），分别为90.7%和73%]，肿瘤芽生是DFS较差的独立预测因素。总之，在大型病理机构中，在全细胞角蛋白玻片上评估肿瘤芽生是可行的，并导致与临床病理特征的预期关联。此外，它是II期患者预后不良的独立预测因素，应在未来临床研究中考虑用于风险分层。
