Tumor Budding: The Name is EMT. Partial EMT

Overview

Journal J Clin Med

Specialty General Medicine

Date 2016 May 3

PMID 27136592

Citations 235

Authors

Alexandru Dan Grigore

Mohit Kumar Jolly

Dongya Jia

Mary C Farach-Carson

Herbert Levine

Affiliations

Soon will be listed here.

Abstract

Tumor budding is a histological phenomenon encountered in various cancers, whereby individual malignant cells and/or small clusters of malignant cells are seen in the tumor stroma. Postulated to be mirror epithelial-mesenchymal transition, tumor budding has been associated with poor cancer outcomes. However, the vast heterogeneity in its exact definition, methodology of assessment, and patient stratification need to be resolved before it can be routinely used as a standardized prognostic feature. Here, we discuss the heterogeneity in defining and assessing tumor budding, its clinical significance across multiple cancer types, and its prospective implementation in clinical practice. Next, we review the emerging evidence about partial, rather than complete, epithelial-mesenchymal phenotype at the tumor bud level, and its connection with tumor proliferation, quiescence, and stemness. Finally, based on recent literature, indicating a co-expression of epithelial and mesenchymal markers in many tumor buds, we posit tumor budding to be a manifestation of this hybrid epithelial/mesenchymal phenotype displaying collective cell migration.

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References

Ueno H, Mochizuki H, Hatsuse K, Hase K, Yamamoto T . Indicators for treatment strategies of colorectal liver metastases. Ann Surg. 2000; 231(1):59-66. PMC: 1420966. DOI: 10.1097/00000658-200001000-00009. View

Palmqvist R, Rutegard J, Bozoky B, Landberg G, Stenling R . Human colorectal cancers with an intact p16/cyclin D1/pRb pathway have up-regulated p16 expression and decreased proliferation in small invasive tumor clusters. Am J Pathol. 2000; 157(6):1947-53. PMC: 3277300. DOI: 10.1016/S0002-9440(10)64833-X. View

Brabletz T, Jung A, Reu S, Porzner M, Hlubek F, Kunz-Schughart L . Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Natl Acad Sci U S A. 2001; 98(18):10356-61. PMC: 56965. DOI: 10.1073/pnas.171610498. View

Jung A, Schrauder M, Oswald U, Knoll C, Sellberg P, Palmqvist R . The invasion front of human colorectal adenocarcinomas shows co-localization of nuclear beta-catenin, cyclin D1, and p16INK4A and is a region of low proliferation. Am J Pathol. 2001; 159(5):1613-7. PMC: 1867079. DOI: 10.1016/s0002-9440(10)63007-6. View

Ueno H, Murphy J, Jass J, Mochizuki H, Talbot I . Tumour 'budding' as an index to estimate the potential of aggressiveness in rectal cancer. Histopathology. 2002; 40(2):127-32. DOI: 10.1046/j.1365-2559.2002.01324.x. View

Okuyama T, Oya M, Yamaguchi M . Budding (sprouting) as a useful prognostic marker in colorectal mucinous carcinoma. Jpn J Clin Oncol. 2002; 32(10):412-6. DOI: 10.1093/jjco/hyf089. View

Valdes F, Alvarez A, Locascio A, Vega S, Herrera B, Fernandez M . The epithelial mesenchymal transition confers resistance to the apoptotic effects of transforming growth factor Beta in fetal rat hepatocytes. Mol Cancer Res. 2002; 1(1):68-78. View

Jass J, Barker M, Fraser L, Walsh M, Whitehall V, Gabrielli B . APC mutation and tumour budding in colorectal cancer. J Clin Pathol. 2002; 56(1):69-73. PMC: 1769852. DOI: 10.1136/jcp.56.1.69. View

Okuyama T, Oya M, Ishikawa H . Budding as a useful prognostic marker in pT3 well- or moderately-differentiated rectal adenocarcinoma. J Surg Oncol. 2003; 83(1):42-7. DOI: 10.1002/jso.10230. View

10.

Tanaka M, Hashiguchi Y, Ueno H, Hase K, Mochizuki H . Tumor budding at the invasive margin can predict patients at high risk of recurrence after curative surgery for stage II, T3 colon cancer. Dis Colon Rectum. 2003; 46(8):1054-9. DOI: 10.1007/s10350-004-7280-z. View

11.

Imai T . Growth patterns in human carcinoma. Their classification and relation to prognosis. Obstet Gynecol. 1960; 16:296-308. View

12.

Vega S, Morales A, Ocana O, Valdes F, Fabregat I, Nieto M . Snail blocks the cell cycle and confers resistance to cell death. Genes Dev. 2004; 18(10):1131-43. PMC: 415638. DOI: 10.1101/gad.294104. View

13.

Benson 3rd A, Schrag D, Somerfield M, Cohen A, Figueredo A, Flynn P . American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004; 22(16):3408-19. DOI: 10.1200/JCO.2004.05.063. View

14.

Roh M, Lee J, Choi P . Tumor budding as a useful prognostic marker in esophageal squamous cell carcinoma. Dis Esophagus. 2004; 17(4):333-7. DOI: 10.1111/j.1442-2050.2004.00436.x. View

15.

Wang H, Liang W, Lin T, Chen W, Jiang J, Yang S . Curative resection of T1 colorectal carcinoma: risk of lymph node metastasis and long-term prognosis. Dis Colon Rectum. 2005; 48(6):1182-92. DOI: 10.1007/s10350-004-0935-y. View

16.

Park K, Choi H, Roh M, Kwon H, Kim C . Intensity of tumor budding and its prognostic implications in invasive colon carcinoma. Dis Colon Rectum. 2005; 48(8):1597-602. DOI: 10.1007/s10350-005-0060-6. View

17.

Prall F, Nizze H, Barten M . Tumour budding as prognostic factor in stage I/II colorectal carcinoma. Histopathology. 2005; 47(1):17-24. DOI: 10.1111/j.1365-2559.2005.02161.x. View

18.

Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T . Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression. Nat Rev Cancer. 2005; 5(9):744-9. DOI: 10.1038/nrc1694. View

19.

Robson E, Khaled W, Abell K, Watson C . Epithelial-to-mesenchymal transition confers resistance to apoptosis in three murine mammary epithelial cell lines. Differentiation. 2006; 74(5):254-64. DOI: 10.1111/j.1432-0436.2006.00075.x. View

20.

Shinto E, Jass J, Tsuda H, Sato T, Ueno H, Hase K . Differential prognostic significance of morphologic invasive markers in colorectal cancer: tumor budding and cytoplasmic podia. Dis Colon Rectum. 2006; 49(9):1422-30. DOI: 10.1007/s10350-006-0595-1. View