Indian Journal of Pathology and Microbiology

: 2019  |  Volume : 62  |  Issue : 2  |  Page : 195--196

Expanding the scope of tumor budding

Antonio DAntonio1, Alessandro Caputo2,  
1 Department of Pathology and Cytopathology, University Hospital “S. Giovanni di Dio e Ruggi D'Aragona”, Salerno, Italy
2 Department of Medicine and Surgery, University of Salerno, Salerno, Italy

Correspondence Address:
Antonio DAntonio
Unit of Pathology and Cytopathology, University Hospital S. Giovanni di Dio e Ruggi D'Aragona. Largo Città di Ippocrate - 84131 Salerno

How to cite this article:
DAntonio A, Caputo A. Expanding the scope of tumor budding.Indian J Pathol Microbiol 2019;62:195-196

How to cite this URL:
DAntonio A, Caputo A. Expanding the scope of tumor budding. Indian J Pathol Microbiol [serial online] 2019 [cited 2022 Aug 16 ];62:195-196
Available from:

Full Text

The tendency of neoplastic glands to infiltrate the stroma individually or in small clusters at the invading front of a tumor is termed “tumor budding.”[1] In the context of colorectal adenocarcinoma, tumor budding is graded according to the number of buds (defined as aggregates of 1–4 cells) in a 0.785 mm2 hotspot.[2] Tumor budding can be considered a marker of the invasiveness of a tumor, with tumors displaying higher numbers of buds being associated with more frequent lymph nodal metastases, as well as distant metastases and local recurrence.[2]

In the context of breast cancer, tumor budding has also been shown to be an independent predictor of lymphovascular invasion, lymph nodal metastases, and worse clinical outcome.[3],[4],[5],[6] However, in contrast to what has taken place in the field of colorectal cancer, no consensus has been reached yet for the usage of tumor budding in the clinical practice of breast cancer.

Genetically, tumor buds have been shown to undergo (at least partial) epithelial-mesenchymal transition, with loss of E-cadherin and membranous β-catenin, which would explain their propensity to invade the stroma in small clusters.[3] These observations can give a biological explanation to link between tumor budding and adverse prognostic features.

Despite being most used in the field of colorectal cancer, tumor budding is a characteristic shared by many carcinomas, including those affecting the esophagus, head and neck, breast, uterus, pancreas, and lung.[7] But it is likely that tumor budding is even more common than is currently thought. For example, the Gleason grading system for prostate cancer is based on architectural features of neoplastic glands: well-formed glands constitute Gleason pattern 3, while a number of different architectural features constitute patterns 4 and 5. Among the architectural features which would be graded as pattern 4 is “malformed glands,” which closely resembles tumor buds composed of clusters of cells. Similarly, single-cell tumor buds would be included in pattern 5.[8] What is remarkable is that a prostate adenocarcinoma composed only of pattern 3 is practically devoid of metastatic potential,[9] whereas the presence of any amount of patterns 4 or 5 confers a worse prognosis, with a higher risk of lymph nodal metastases, local recurrence, and a lower progression-free survival.[8] In other words, in the context of a prostate adenocarcinoma composed mostly of well-formed glands, having “tumor buds” on the invasive front would mean the difference between a cancer with no metastatic potential (Gleason score 3 + 3 = 6) and an aggressive cancer that requires radical therapy and close follow-up (Gleason score ≥7). If we were for a moment to forego the Gleason grading system and assess prostate cancer morphologically and architecturally, we could easily see how tumor budding constitutes an adverse prognostic factor in prostate cancer.

An extreme form of budding is exemplified by cancers which show a loss of E-cadherin, such as lobular breast adenocarcinoma and diffuse-type gastric adenocarcinoma, which display a remarkable ability to infiltrate the surrounding tissues.

In conclusion, tumor budding is a directly visible, morphologic consequence of a series of genetic alterations which result in increased aggressiveness and invasiveness of a tumor. Tumor budding is an exciting marker, which requires nothing more than an hematoxylin and eosin-stained slide to assess, and with important prognostic implications for many human tumors. More validation studies and consensus guidelines are required to take advantage of this important marker in clinical practice.


1Lugli A, Karamitopoulou E, Zlobec I. Tumour budding: A promising parameter in colorectal cancer. Br J Cancer 2012;106:1713-7.
2Lugli A, Kirsch R, Ajioka Y, Bosman F, Cathomas G, Dawson H, et al. Recommendations for reporting tumor budding in colorectal cancer based on the international tumor budding consensus conference (ITBCC) 2016. Mod Pathol 2017;30:1299-311.
3Liang 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;209:269-75.
4Salhia B, Trippel M, Pfaltz K, Cihoric N, Grogg A, Lädrach C, et al. High tumor budding stratifies breast cancer with metastatic properties. Breast Cancer Res Treat 2015;150:363-71.
5Gujam F, McMillan D, Mohammed Z, Edwards J, Going J. The relationship between tumour budding, the tumour microenvironment and survival in patients with invasive ductal breast cancer. Br J Cancer 2015;113:1066.
6Tumor budding in invasive breast cancer - an indispensable budding touchstone. Indian J Pathol Microbiol 2019;1:1-1.
7Grigore A, Jolly M, Jia D, Farach-Carson M, Levine H. Tumor budding: The name is EMT. Partial EMT. J Clin Med 2016;5:51.
8Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA, et al. The 2014 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma: Definition of grading patterns and proposal for a new grading system. Am J Surg Pathol 2016;40:244-52.
9Ross HM, Kryvenko ON, Cowan JE, Simko JP, Wheeler TM, Epstein JI. Do adenocarcinomas of the prostate with Gleason score (GS) ≤ 6 have the potential to metastasize to lymph nodes? Am J Surg Pathol 2012;36:1346-52.