CC BY-NC-ND 4.0 · J Lab Physicians 2022; 14(04): 485-490
DOI: 10.1055/s-0042-1747676
Original Article

A Retrospective Study of Association of Tumor Budding, Tumor Microenvironment, and Clinicopathological Characteristics of Invasive Breast Carcinoma

Tanwi Singh
1   Pathology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
Kalpana Chandra
1   Pathology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
Nidhish Kumar
1   Pathology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
Anuja Mishra
1   Pathology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
Sanjeet Singh
1   Pathology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
Anju Singh
1   Pathology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
Umesh Kumar
1   Pathology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
Praveen Kumar
2   General Medicine, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
› Author Affiliations


Background Tumor budding (TB) has been identified in many solid cancers and thought to be involved in invasion and is the initial step in the metastatic process. Limited information is available documenting the role of tumor budding in breast carcinoma. With this aim, the present study evaluates the association of tumor budding, tumor microenvironment, and its correlation with clinicopathologic parameters.

Materials and Methods A total of 102 cases were archived and evaluated for peripheral and intra tumoral budding along with tumor microenvironment on hematoxylin and eosin (H&E) slides.

Statistical Analysis Correlation between tumor budding, tumor microenvironment, and other classical clinicopathological parameters was studied by Chi-square test. A p-value less than 0.05 was considered significant.

Results Females constituted 99 cases out of 102 and 3 were males. We found 55.9% and 44.1% of patients in the age group less than or equal to 50 and greater than 50, respectively. Also, 65.6% of cases presented with small tumor size less than or equal to 5 cm, 80.39% with lymph node metastasis, and 76.4% with lympho-vascular emboli. High peripheral tumoral budding (PTB) was seen in 45.10%, low peripheral tumoral budding in 54.9%, high ITB in 53.9%, and low ITB in 46.1%. Necrosis was found only in 39.21%. Significant statistical association of PTB was found with lymph node metastasis, lymphovascular emboli, and tumor necrosis, whereas ITB with tumor grade, lymph node metastasis, lympho-vascular emboli, and necrosis. Both PTB and ITB showed no statistically significant correlation with age and size of the tumor.

Conclusion Tumor budding is an independent adverse prognostic factor in invasive breast carcinoma. However, further work is needed to establish a standard method for the quantification of this parameter, which will help in effective stratification of patients in terms of disease-free survival and likely outcome.

Publication History

Article published online:
10 June 2022

© 2022. The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

  • References

  • 1 Cree IA, Lokuhetty D. WHO Classification of Tumours Editorial Board. Breast Tumors. . 5th ed. Lyon (France): International Agency for Research and Cancer; 2019: 83
  • 2 Liang F, Cao W, Wang Y, Li L, Zhang G, Wang Z. The prognostic value of tumor budding in invasive breast cancer. Pathol Res Pract 2013; 209 (05) 269-275
  • 3 Laedrach C, Salhia B, Cihoric N, Zlobec I, Tapia C. Immunophenotypic profile of tumor buds in breast cancer. Pathol Res Pract 2018; 214 (01) 25-29
  • 4 Grigore AD, Jolly MK, Jia D, Farach-Carson MC, Levine H. Tumor budding: the name is EMT. Partial EMT. J Clin Med 2016; 5 (05) 51
  • 5 Ozer SP, Barut SG, Ozer B, Catal O, Sit M. The relationship between tumor budding and survival in colorectal carcinomas. Rev Assoc Med Bras (1992) 2019; 65 (12) 1442-1447
  • 6 Salhia B, Trippel M, Pfaltz K. et al. High tumor budding stratifies breast cancer with metastatic properties. Breast Cancer Res Treat 2015; 150 (02) 363-371
  • 7 Gujam FJ, McMillan DC, Mohammed ZM, Edwards J, Going JJ. The relationship between tumour budding, the tumour microenvironment and survival in patients with invasive ductal breast cancer. Br J Cancer 2015; 113 (07) 1066-1074
  • 8 Masilamani S, Kanmani P. Evaluation of clinicopathologic significance of tumor budding in breast carcinoma. International Journal of Clinical and Diagnostic Pathology 2019; 2 (01) 171-173
  • 9 Klintrup K, Mäkinen JM, Kauppila S. et al. Inflammation and prognosis in colorectal cancer. Eur J Cancer 2005; 41 (17) 2645-2654
  • 10 Zlobec I, Lugli A. Epithelial mesenchymal transition and tumor budding in aggressive colorectal cancer: tumor budding as oncotarget. Oncotarget 2010; 1 (07) 651-661
  • 11 Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ. eds. WHO classification of tumours of the breast. 4th ed. Lyon: IARC Press; 2012
  • 12 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
  • 13 Amin MB, Edge SB, Greene FL. AJCC Cancer Staging Manual. . 8th ed. New York: Springer; 2017
  • 14 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
  • 15 van Wyk HC, Park J, Roxburgh C, Horgan P, Foulis A, McMillan DC. The role of tumour budding in predicting survival in patients with primary operable colorectal cancer: a systematic review. Cancer Treat Rev 2015; 41 (02) 151-159
  • 16 Kumarguru BN, Ramaswamy AS, Shaik S, Karri A, Srinivas VS, Prashant BM. Tumor budding in invasive breast cancer - an indispensable budding touchstone. Indian J Pathol Microbiol 2020; 63 (Supplement): S117-S122
  • 17 Sriwidyani N, Manuaba I, Alit-Artha I, Mantik-Astawa I. Tumor budding in breast carcinoma: relation to E-Cadherin, MMP-9 expression, and metastasis risk. Bali Medical Journal 2016; 5 (03) 497-501
  • 18 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
  • 19 Renuka IV, Madhavi K, Premalatha P, Krishnamacharyulu PAV, Vaishnavi R. Tumor budding in invasive carcinoma of breast of no special type (NST): value as a prognostic factor. IP Journal of Diagnostic Pathology and Oncology 2019; 4 (02) 125-129