Tumour budding as prognostic factor in stage I/II colorectal carcinoma

Abstract

This study confirms the prognostic value of budding in a contemporary series of colorectal carcinomas that by TNM were low risk. Technically easy, rapid and robust to determine, budding quantified in pan-cytokeratin stains significantly aids in the identification of high-risk patients and is recommended for more general use in surgical pathology.

Tumor budding in colorectal carcinoma: time to take notice

“…In one of the earlier studies of tumor budding, Hase et al 18 demonstrated that 5-year survival rates of Dukes B (stage II, T3-4 N0) patients with high-grade budding are significantly worse than those of Dukes C (N þ ) patients without budding (29 percent vs 66 percent; Po0.001). A number of more recent studies have confirmed that patients with Stage II colorectal carcinoma do significantly worse when high-grade budding is present, [34][35][36]38,41,45 and several studies have shown that survival rates of patients with Stage II colorectal carcinoma with high-grade budding are equivalent to survival rates of patients with Stage III colorectal carcinoma. [34][35][36] In their studies of Stage II and III pT3 tumors, Okuyama et al 34,35 found that tumor budding was the only factor on multivariate analysis to be associated with decreased survival and was more prognostically significant than lymph node metastases.…”

“…Similarly, the presence of budding has been associated with increased risk of distant metastases, [34][35][36] suggesting that budding may also be associated with vascular invasion. A few tumor-budding studies have used vascular markers and/or elastic stains to assess vascular invasion, 11,12,19,22,26,32,37,38 but only four have analyzed the relationship between budding and vascular invasion: Kazama et al 22 found no relationship between budding and vascular invasion, whereas three other studies have reported a statistically significant correlation between budding and venous invasion, though the association was not as pronounced as the relationship with lymphatic invasion and lymph node metastases. 11,12,32 The tumor-host interaction at the invasive front may be of prognostic importance in the setting of tumor budding.…”

“…11,12,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] On multivariate analysis, budding has consistently emerged as an independent adverse prognostic factor, associated with local tumor recurrence and distant metastases, and significantly worse overall and disease-free survival. 12,15,16,21,27,28,31,32,[34][35][36]38,40,41 The adverse prognostic impact of high-grade tumor budding is seen in both early and advanced colorectal carcinoma, and there are several scenarios in which this feature might influence clinical decision making, particularly in early colorectal carcinoma.…”

“…The most widely cited scoring system, developed by Ueno et al, 27 defines 'high-grade budding' as 410 buds composed of fewer than 5 cells in a 25 Â field (field area ¼ 0.385 mm 2 ). Other authors have defined buds as being composed of r5 cells, 38 while some have not set an upper cell limit and instead count both single cells and bundles of five or more cells as buds, as proposed by Morodomi et al 11 and commonly applied in the Japanese literature. This heterogeneity in defining budding is compounded by the use of varying field diameters and cutoffs for defining 'high-grade' budding, especially when a score is given as #/hpf rather than/mm 2 .…”

“…12,13,22,23,31,32,38,40,43,44,48,51,54,55 The use of immunohistochemistry in the assessment of budding is somewhat controversial: some authors argue that the evaluation of budding should be limited to H&E-stained slides because of the cost and impracticality of performing immunohistochemistry in routine cases, while others argue that immunohistochemistry should be used routinely to improve the accuracy and reproducibility of bud counts. In addition to cost considerations, the use of immunohistochemistry may also require the establishment of a separate cutoff for defining positive budding.…”