Morphology and prognostic value of tumor budding in rectal cancer after neoadjuvant radiotherapy

Du, Changsheng; Xue, Weicheng; Li, Jiyou; Cai, Yong; Gu, Jin

doi:10.1016/j.humpath.2011.07.026

Cited by 26 publications

(25 citation statements)

References 27 publications

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“…In this study, the biomarker patterns would be consistent with the adverse effect of an invasive and migratory EMT phenotype, being further associated with adverse pathological features of higher T‐stage, extramural vascular invasion and tumour budding. Tumour budding has been previously associated with poor outcome of colorectal cancer , including the distinct morphological and prognostic significance of postirradiation budding in rectal cancer . The present study further defines its important biological relationship with EMT, with the motile phenotype potentially leading to tumour budding, distinct from the main tumour mass.…”

Section: Discussionsupporting

confidence: 60%

The role of epithelial mesenchymal transition and resistance to neoadjuvant therapy in locally advanced rectal cancer

et al. 2014

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Section: Discussionsupporting

confidence: 60%

The role of epithelial mesenchymal transition and resistance to neoadjuvant therapy in locally advanced rectal cancer

et al. 2014

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“…33,34 This study demonstrates that budding in the initial biopsy predicts residual adverse features post neoadjuvant chemoradiotherapy (higher ypT stage, positive lymph nodes, poorly differentiated tumors and lymphovascular invasion). Intra-tumoral budding was associated with tumor regression grade Tumor budding has a sensitivity, specificity, positive predictive value and negative predictive value of 23.38, 100, 100 and 16.90%, respectively for determining non-response to neoadjuvant chemoradiotherapy.…”

Section: Discussionmentioning

confidence: 72%

Prognostic significance of tumor budding in rectal cancer biopsies before neoadjuvant therapy

et al. 2014

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Tumor budding is an increasingly important prognostic feature for pathologists to recognize. The aim of this study was to correlate intra-tumoral budding in pre-treatment rectal cancer biopsies with pathological response to neoadjuvant chemoradiotherapy and with long-term outcome. Data from a prospectively maintained database were acquired from patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy. Pre-treatment rectal biopsies were retrospectively reviewed for evidence of intra-tumoral budding. Multivariate logistic regression was used to identify factors contributing to cancer-specific death, expressed as hazard ratios with 95% confidence intervals. Of the 185 patients with locally advanced rectal cancer, 89 patients met the eligibility criteria, of whom 18 (20%) exhibited budding in a pre-treatment tumor biopsy. Intra-tumoral budding predicted a poor pathological response to neoadjuvant chemoradiotherapy (higher ypT stage, P ¼ 0.032; lymph node involvement, P ¼ 0.018; lymphovascular invasion, P ¼ 0.004; and residual poorly differentiated tumors, P ¼ 0.005). No patient with intra-tumoral budding exhibited a tumor regression grade 1 or complete pathological response, providing a 100% specificity and positive predictive value for non-response to neoadjuvant chemoradiotherapy. Intra-tumoral budding was associated with a lower disease-free 5-year survival rate (33 vs 78%, Po0.001), cancer-specific 5-year survival rate (61 vs 87%, P ¼ 0.021) and predicted cancer-specific death (hazard ratio 3.51, 95% confidence interval 1.03-11.93, P ¼ 0.040). Intratumoral budding at diagnosis of rectal cancer identifies those who will poorly respond to neoadjuvant chemoradiotherapy and those with a poor prognosis.

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“…Budding has been shown to be a negative prognostic factor for survival in different kinds of study designs and for a broad range of cut-offs. However, most of the previous studies could demonstrate effects on survival only in univariate analysis or limited to disease free survival [15][16][17][18][19]. Including patients with complete response in the analysis appeared to attenuate the prognostic impact of tumor budding.…”

Section: Discussionmentioning

confidence: 95%

“…Budding has been described as a prognostic feature after chemoradiotherapy in rectal cancer patients in several publications with the general limitation of a retrospective study design. In previous studies, budding was reported in 10.1-63.2% of cases due to different methodologies used for evaluation [3,[15][16][17][18][19][20]. Budding has been shown to be a negative prognostic factor for survival in different kinds of study designs and for a broad range of cut-offs.…”

Section: Discussionmentioning

confidence: 99%

Tumor budding outperforms ypT and ypN classification in predicting outcome of rectal cancer after neoadjuvant chemoradiotherapy

et al. 2019

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Background: Budding is a complementary prognostic factor for colorectal cancer. In this study, we aimed to clarify the role of tumor budding in rectal cancer patients after preoperative chemoradiotherapy. Methods: A total of 124 patients with rectal cancer treated with neoadjuvant chemoradiotherapy and consecutive surgery were included. Surgical specimens were evaluated for budding and routine clinicopathological features. Budding was evaluated on hematoxylin and eosin (H&E)-stained slides and by cytokeratin immunohistochemical (IHC) staining. Results: A budding rate of 36.9% (n = 38) by H&E and 55.6% (n = 55) by IHC was observed. Budding was significantly associated with a high ypT and ypN status, poor differentiation, and low degrees of tumor regression. Moreover, budding was strongly predictive of a worse patient outcome, as measured by tumor recurrence or death. In multivariate analyses, budding remained the only significant parameter for overall survival and was even superior to the ypT and ypN status (budding in H&E: hazard ratio (HR) 2.72, 95% confidence interval (95% CI) 1.15-6.44, p = 0.023; budding in IHC: HR 5.19, 95% CI 1.62-16.61, p = 0.006). Conclusion: Budding is a strong prognostic predictor of survival in rectal cancer patients after neoadjuvant therapy. A standardized evaluation of tumor budding after neoadjuvant therapy may thus aid in risk stratification and guide the clinical management of patients with rectal cancer. Immunostaining can help to enhance the diagnostic accuracy and prognostic significance.

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Morphology and prognostic value of tumor budding in rectal cancer after neoadjuvant radiotherapy

Cited by 26 publications

References 27 publications

The role of epithelial mesenchymal transition and resistance to neoadjuvant therapy in locally advanced rectal cancer

The role of epithelial mesenchymal transition and resistance to neoadjuvant therapy in locally advanced rectal cancer

Prognostic significance of tumor budding in rectal cancer biopsies before neoadjuvant therapy

Tumor budding outperforms ypT and ypN classification in predicting outcome of rectal cancer after neoadjuvant chemoradiotherapy

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