Translational Research Unit (TRU), Institute of Pathology, University of Bern, Bern, Switzerland.
Department of Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland.
Br J Cancer. 2014 Feb 18;110(4):1008-13. doi: 10.1038/bjc.2013.797. Epub 2013 Dec 24.
In colorectal cancer (CRC), tumour budding at the invasion front is associated with lymph node (LN) and distant metastasis. Interestingly, tumour budding can also be detected in biopsies (intratumoural budding; ITB) and may have similar clinical importance. Here we investigate whether ITB in preoperative CRC biopsies can be translated into daily diagnostic practice.
Preoperative biopsies from 133 CRC patients (no neoadjuvant therapy) underwent immunohistochemistry for pan-cytokeratin marker AE1/AE3. Across all biopsies for each patient, the densest region of buds at × 40 (high-power field; HPF) was identified and buds were counted.
A greater number of tumour buds in the biopsy was associated with pT stage (P=0.0143), LN metastasis (P=0.0007), lymphatic (P=0.0065) and venous vessel invasion (P=0.0318) and distant metastasis (cM1) (P=0.0013). Using logistic regression, a 'scale' was developed to estimate the probability of LN and distant metastasis using the number of tumour buds (e.g. 10 buds per HPF: 64% chance of LN metastasis; 30 buds per HPF: 86% chance). Inter-observer agreement for ITB was excellent (intraclass correlation coefficient: 0.813).
Tumour budding can be assessed in the preoperative biopsy of CRC patients. It is practical, reproducible and predictive of LN and distant metastasis. Intratumoural budding qualifies for further investigation in the prospective setting.
在结直肠癌（CRC）中，肿瘤在侵袭前沿的芽生与淋巴结（LN）和远处转移有关。有趣的是，肿瘤芽生也可以在活检中检测到（肿瘤内芽生；ITB），并且可能具有相似的临床重要性。在这里，我们研究术前 CRC 活检中的 ITB 是否可以转化为日常诊断实践。
对 133 例（无新辅助治疗）CRC 患者的术前活检进行细胞角蛋白标志物 AE1/AE3 的免疫组织化学染色。对每位患者的所有活检，确定最密集的芽生区域（×40 高倍视野；HPF）并计数芽生数。
活检中肿瘤芽生数与 pT 分期（P=0.0143）、LN 转移（P=0.0007）、淋巴管（P=0.0065）和静脉血管侵犯（P=0.0318）以及远处转移（cM1）（P=0.0013）相关。使用逻辑回归，开发了一种“量表”，使用肿瘤芽生数估计 LN 和远处转移的概率（例如，每 HPF 有 10 个芽生：LN 转移的可能性为 64%；每 HPF 有 30 个芽生：LN 转移的可能性为 86%）。ITB 的观察者间一致性极好（组内相关系数：0.813）。
肿瘤芽生可在 CRC 患者的术前活检中进行评估。它具有实用性、可重复性和预测 LN 和远处转移的能力。肿瘤内芽生有资格在前瞻性研究中进一步研究。
