Evaluation of Applicability of Tumor Budding and Poorly Differentiated Clusters as Additional Prognostic Markers in Colorectal Cancers

Abstract

Purpose

Very few studies have assessed tumor budding (TB) and poorly differentiated cell clusters (PDCs) simultaneously in colorectal cancers (CRCs). The goal of this study was to establish a correlation between these two pertinent histological features and to reinforce the importance of their incorporation in routine histopathological reporting of CRC cases as a means to predict clinical outcome.

Methods

Resection specimens of colorectal carcinoma were included in the study. Patients who received presurgical therapy, or refused consent were excluded. PDC and TB were evaluated in routine hematoxylin and eosin-stained histopathological sections taken from the advancing edge of the tumor. TB and PDC were reported by selecting a “hotspot” chosen after review of all available slides with invasive tumor. It was then followed by their correlation with other known prognostic factors.

Results

Spearman's rho calculator for strength of association between TB and PDC as well as association of TB and PDC individually with known prognostic factors revealed statistical significance. Correlation of TB and PDC with histologic grade, primary tumor (pT), and regional lymph node (pN) stage was done based on one-way analysis of variance calculator, which yielded statistically significant results.

Conclusion

Evaluation of these two histological parameters in the same hotspot field at the tumor invasive front plays a fundamental role in the definition of cancer aggressiveness and prediction of tumor behavior.

Keywords

colorectal cancers (CRC) - morphology - tumor budding (TB) - poorly differentiated cell cluster (PDC) - prognostic markers

Authors' Contributions

S.S. helped in study conception and design, material preparation, data collection, and analysis, written first draft of the manuscript; whereas R.G. and S.C. was involved in study conception and design, material preparation, data collection, and analysis.

Informed Consent

Informed consent was obtained from all participants included in the study.

Ethical Approval

The Institutional Ethics Committee has approved the study.

Publikationsverlauf

Eingereicht: 15. Juli 2023

Angenommen: 11. Juni 2024

Artikel online veröffentlicht:
03. Juli 2024

• References

• 1 Zlobec I, Lugli A. Tumour budding in colorectal cancer: molecular rationale for clinical translation. Nat Rev Cancer 2018; 18 (04) 203-204
• 2 Lugli A, Kirsch R, Ajioka Y. et al. Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Mod Pathol 2017; 30 (09) 1299-1311
• 3 Ueno H, Kajiwara Y, Shimazaki H. et al. New criteria for histologic grading of colorectal cancer. Am J Surg Pathol 2012; 36 (02) 193-201
• 4 Hase K, Shatney C, Johnson D, Trollope M, Vierra M. Prognostic value of tumor “budding” in patients with colorectal cancer. Dis Colon Rectum 1993; 36 (07) 627-635
• 5 Mitrovic B, Schaeffer DF, Riddell RH, Kirsch R. Tumor budding in colorectal carcinoma: time to take notice. Mod Pathol 2012; 25 (10) 1315-1325
• 6 Zlobec I, Lugli A. Prognostic and predictive factors in colorectal cancer. Postgrad Med J 2008; 84 (994) 403-11
• 7 Jass JR, Barker M, Fraser L. et al. APC mutation and tumour budding in colorectal cancer. J Clin Pathol 2003; 56 (01) 69-73
• 8 Okuyama T, Nakamura T, Yamaguchi M. Budding is useful to select high-risk patients in stage II well-differentiated or moderately differentiated colon adenocarcinoma. Dis Colon Rectum 2003; 46 (10) 1400-1406
• 9 Ueno H, Price AB, Wilkinson KH, Jass JR, Mochizuki H, Talbot IC. A new prognostic staging system for rectal cancer. Ann Surg 2004; 240 (05) 832-839
• 10 Zlobec I, Minoo P, Terracciano L, Baker K, Lugli A. Characterization of the immunological microenvironment of tumour buds and its impact on prognosis in mismatch repair-proficient and -deficient colorectal cancers. Histopathology 2011; 59 (03) 482-495
• 11 Ueno H, Hase K, Hashiguchi Y. et al. Site-specific tumor grading system in colorectal cancer: multicenter pathologic review of the value of quantifying poorly differentiated clusters. Am J Surg Pathol 2014; 38 (02) 197-204
• 12 Barresi V, Bonetti LR, Ieni A, Branca G, Baron L, Tuccari G. Histologic grading based on counting poorly differentiated clusters in preoperative biopsy predicts nodal involvement and pTNM stage in colorectal cancer patients. Hum Pathol 2014; 45 (02) 268-275
• 13 Barresi V, Branca G, Ieni A. et al. Poorly differentiated clusters (PDCs) as a novel histological predictor of nodal metastases in pT1 colorectal cancer. Virchows Arch 2014; 464 (06) 655-662
• 14 Barresi V, Reggiani Bonetti L, Branca G, Di Gregorio C, Ponz de Leon M, Tuccari G. Colorectal carcinoma grading by quantifying poorly differentiated cell clusters is more reproducible and provides more robust prognostic information than conventional grading. Virchows Arch 2012; 461 (06) 621-628
• 15 Marx AH, Mickler C, Sauter G. et al. High-grade intratumoral tumor budding is a predictor for lymphovascular invasion and adverse outcome in stage II colorectal cancer. Int J Colorectal Dis 2020; 35 (02) 259-268
• 16 Lugli A, Vlajnic T, Giger O. et al. Intratumoral budding as a potential parameter of tumor progression in mismatch repair-proficient and mismatch repair-deficient colorectal cancer patients. Hum Pathol 2011; 42 (12) 1833-1840
• 17 Zlobec I, Hädrich M, Dawson H. et al. Intratumoural budding (ITB) in preoperative biopsies predicts the presence of lymph node and distant metastases in colon and rectal cancer patients. Br J Cancer 2014; 110 (04) 1008-1013
• 18 Archilla I, Díaz-Mercedes S, Aguirre JJ. et al. Lymph node tumor burden correlates with tumor budding and poorly differentiated clusters: a new prognostic factor in colorectal carcinoma?. Clin Transl Gastroenterol 2021; 12 (03) e00303
• 19 Mohan N, Kalaranjini KV, Mohandas L. Assessment of tumour budding in colorectal carcinoma and its correlation with pathological staging among patients undergoing resection at a tertiary care hospital in Kerala, India. J Clin Diagn Res 2023; 17 (10) EC01-EC07
• 20 Maurya S, Patel S, Srikantegowda H. A study of significance of poorly differentiated clusters in colorectal carcinomas: association with histopathological prognostic factors. J Clin Diagn Res 2020; 14 (11) EC28-EC32
• 21 Shah AH, Gami AJ, Desai NH, Gandhi JS, Trivedi PP. Tumor budding as a prognostic indicator in colorectal carcinoma: a retrospective study of primary colorectal carcinoma cases in a tertiary care center. Indian J Surg Oncol 2022; 13 (03) 459-467
• 22 Terry S, Savagner P, Ortiz-Cuaran S. et al. New insights into the role of EMT in tumor immune escape. Mol Oncol 2017; 11 (07) 824-846
• 23 Chae YK, Chang S, Ko T. et al. Epithelial-mesenchymal transition (EMT) signature is inversely associated with T-cell infiltration in non-small cell lung cancer (NSCLC). Sci Rep 2018; 8 (01) 2918