Tumor Budding is a Strong and Reproducible Prognostic Marker in T3N0 Colorectal Cancer

Abstract

Tumor budding is a strong, reproducible, and independent prognostic marker of outcome that is easily assessed on hematoxylin and eosin slides. This may be useful for identifying the subset of T3N0M0 patients at high risk of recurrence who may benefit from adjuvant therapy.

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.…”

“…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 QUASAR trial demonstrated that chemotherapy does result in increased survival in Stage II patients, but the improvement was small and may not justify the costs and side effects of chemotherapy in all patients. 46 The significantly worse outcome experienced by Stage II patients with tumor budding has prompted some authors to suggest that adjuvant chemotherapy should be considered in these patients, 18,[34][35][36]41 but there are no published data assessing the effectiveness of chemotherapy in Stage II colorectal carcinoma with tumor budding.…”

“…A few studies on tumor budding have incorporated an assessment of interobserver variability, with reported kappa values ranging from 0.41 to 0.938. 15,27,32,34,38,41,48 Kappa values, a commonly used measure of interobserver agreement, can be interpreted as follows: o0.20, poor; 0.21-0.40, fair; 0.41-0.60, moderate; 0.61-0.80, good; and 40.80, very good. 56 Intuitively, one would expect the use of immunohistochemistry to improve interobserver variability, but studies assessing interobserver variability on immunohistochemically stained slides have reported kappa values ranging from 0.53 to 0.874, 32,38,48 similar to those reported by authors assessing tumour budding on H&E. 15,27,32,34,41 Only one study has directly compared interobserver variability between assessments performed on H&E and immunohistochemically stained slides among the same group of pathologists: when Suzuki et al 32 evaluated budding with both H&E and immunohistochemistry, they showed only a modest improvement in interobserver variability when anti-cytokeratin antibodies were used (k ¼ 0.41 with H&E, and k ¼ 0.53 with immunohistochemistry).…”

Clinicopathologic and molecular features of sporadic early-onset colorectal adenocarcinoma: an adenocarcinoma with frequent signet ring cell differentiation, rectal and sigmoid involvement, and adverse morphologic features

“…The grade of each colonic adenocarcinoma was scored using a two-tiered scheme: low grade, 450% gland formation and high grade, o50% gland formation. Tumor budding assessment was performed using the rapid bud count method: 15 high budding, 450% of areas examined under  200 magnification were positive for budding and low budding, o50% of areas examined under  200 magnification were positive for budding. The presence of tumor-infiltrating lymphocytes was defined as 47 lymphocytes per 10 high-powered fields.…”