Department of Hepatogastroenterology and Gastrointestinal Oncology, University of Paris (Paris Descartes), SIRIC CARPEM, Georges Pompidou European Hospital, AP-HP, Paris, France; Department of Medicine, DAME, University Hospital of Udine, Udine, Italy; Department of Medical Oncology, ULSS8 Berica, Vicenza, Italy.
Department of Pathology, Georges Pompidou European Hospital, AP-HP, Paris, France.
Ann Oncol. 2022 Jun;33(6):628-637. doi: 10.1016/j.annonc.2022.03.002. Epub 2022 Mar 16.
Histological characteristics at the invasive front may reflect tumor aggressiveness; specifically, tumor budding (Bd) is an emerging prognostic biomarker in colon cancer (CC). We explored further the significance of Bd for risk stratification by evaluating survival of stage III CC patients included in the IDEA-France phase III trial.
This post-hoc study was conducted on tissue slides from 1048 stage III CC patients. Bd was scored by central review by the Bd criteria of the 2016 International Tumor Budding Consensus Conference (ITBCC 2016) and classified as Bd1 (0-4 buds/0.785 mm), Bd2 (5-9 buds), and Bd3 (≥10 buds) categories. Disease-free survival (DFS) and overall survival (OS) were analyzed by the log-rank test. Clinicopathological features and Immunoscore® were correlated with Bd.
Overall, Bd1, Bd2, and Bd3 were observed in 39%, 28%, and 33% of CC, respectively. Bd2 and Bd3 were associated with vascular (P = 0.002) and perineural invasions (P = 0.0009). The 3-year DFS and the 5-year OS rates for Bd (1 versus 2-3) were 79.4% versus 67.2% (P = 0.001) and 89.2% versus 80.8% (P = 0.001), respectively. This was confirmed after adjustment for relevant clinicopathological features for DFS [hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.12-1.77, P = 0.003] and OS (HR 1.65, 95% CI 1.22-2.22, P = 0.001). When combined with pTN stage and Immunoscore® subgroups, Bd significantly improved disease prognostication.
Bd demonstrated its independent prognostic value for DFS and OS. Given these findings, Bd as per the ITBCC 2016 should be mandatory in every pathology report in stage III CC patients. Bd and Immunoscore® could play a complementary role in personalized health care in this setting.
侵袭前沿的组织学特征可能反映肿瘤的侵袭性；具体来说，肿瘤芽（Bd）是结肠癌（CC）中新兴的预后生物标志物。我们通过评估 IDEA-France 三期试验中纳入的 III 期 CC 患者的生存情况，进一步探讨了 Bd 对风险分层的意义。
对 1048 例 III 期 CC 患者的组织切片进行了这项回顾性研究。Bd 由中央审查中心按照 2016 年国际肿瘤芽形成共识会议（ITBCC 2016）的 Bd 标准进行评分，并分为 Bd1（0-4 个芽/0.785mm）、Bd2（5-9 个芽）和 Bd3（≥10 个芽）类别。采用对数秩检验分析无病生存（DFS）和总生存（OS）。临床病理特征和免疫评分®与 Bd 相关。
总体而言，CC 中分别观察到 Bd1、Bd2 和 Bd3 的比例为 39%、28%和 33%。Bd2 和 Bd3 与血管（P=0.002）和神经周围浸润（P=0.0009）有关。Bd1 与 Bd2-3 相比，3 年 DFS 和 5 年 OS 率分别为 79.4%与 67.2%（P=0.001）和 89.2%与 80.8%（P=0.001）。在调整与 DFS 相关的临床病理特征后（HR 1.41，95%CI 1.12-1.77，P=0.003）和 OS（HR 1.65，95%CI 1.22-2.22，P=0.001），这一结果得到了证实。当与 pTN 分期和免疫评分®亚组相结合时，Bd 显著改善了疾病预后。
Bd 显示出其对 DFS 和 OS 的独立预后价值。鉴于这些发现，根据 ITBCC 2016 对每例 III 期 CC 患者的病理报告均应强制要求报告 Bd。Bd 和免疫评分®在这种情况下可能在个性化医疗保健中发挥互补作用。
