Proposal for a 10-high-power-fields scoring method for the assessment of tumor budding in colorectal cancer

Abstract

Although tumor budding is linked to adverse prognosis in colorectal cancer, it remains largely unreported in daily diagnostic work due to the absence of a standardized scoring method. Our aim was to assess the interobserver agreement of a novel 10-high-power-fields method for assessment of tumor budding at the invasive front and to confirm the prognostic value of tumor budding in our setting of colorectal cancers. Whole tissue sections of 215 colorectal cancers with full clinico-pathological and follow-up information were stained with cytokeratin AE1/AE3 antibody. Presence of buds was scored across 10-high-power fields at the invasive front by two pathologists and two additional observers were asked to score 50 cases of tumor budding randomly selected from the larger cohort. The measurements were correlated to the patient and tumor characteristics. Inter-observer agreement and correlation between observers' scores were excellent (Po0.0001; intraclass correlation coefficient ¼ 0.96). A test subgroup of 65 patients (30%) was used to define a valid cutoff score for high-grade tumor budding and the remaining 70% of the patients were entered into the analysis. High-grade budding was defined as an average of Z10 buds across 10-high-power fields. High-grade budding was associated with a higher tumor grade (Po0.0001), higher TNM stage (P ¼ 0.0003), vascular invasion (Po0.0001), infiltrating tumor border configuration (Po0.0001) and reduced survival (Po0.0001). Multivariate analysis confirmed its independent prognostic effect (P ¼ 0.007) when adjusting for TNM stage and adjuvant therapy. Using 10-high-power fields for evaluating tumor budding has independent prognostic value and shows excellent inter-observer agreement. Like the BRE and Gleason scores in breast and prostate cancers, respectively, tumor budding could be a basis for a prognostic score in colorectal cancer.

Tumor budding in intestinal-type gastric adenocarcinoma is associated with nodal metastasis and recurrence

“…Tumor Budding in Intestinal Type Gastric Adenocarcinoma -higher tumor budding is consistently linked to adverse pathologic features and clinical outcomes [28,29,30]. Given the wide variety of different methods employed in both colorectal carcinoma and upper gastrointestinal malignancies [15,16,18,21,22,24] that provide largely compatible results, it is reasonable to hypothesize that a single standardized method could be applied to carcinomas throughout the luminal gastrointestinal tract.…”

Tumor Budding Correlates With the Protumor Immune Microenvironment and Is an Independent Prognostic Factor for Recurrence of Stage I Lung Adenocarcinoma

“…13,14 In their attempts to unravel the biologic signifi cance of tumor budding, investigators have noted that tumor budding may be associated with epithelial mesenchymal transition, thereby increasing cancer cell migration and invasion. [15][16][17][18] In breast cancer, immune-induced responses have been shown to promote epithelial mesenchymal transition.…”

“…Tumor budding was defi ned as small tumor nests composed of fewer than fi ve tumor cells ( Fig 2B ) and was quantifi ed by counting 10 highpower fi elds (HPFs) at 3 200 magnifi cation. 13 During evaluation using 10 HPFs, the maximum number of tumor buds per one HPF was considered the number of buds for each tumor. We then classifi ed tumor budding as grade 0 (zero buds per HPF), grade 1 (one to four) ( Fig 2C ), grade 2 (fi ve to nine), or grade 3 ( Ն 10) ( Fig 2D ).…”

Prognostic significance of tumor budding in rectal cancer biopsies before neoadjuvant therapy

“…Recent studies have addressed the role of tumor budding in resected colorectal specimens. [14][15][16] Tumor budding within the entire tumor, rather than at the invasive front, is termed intra-tumoral budding 17 and has been described in both colorectal cancer biopsy and resected specimens. 18,19 This study addresses the prognostic and predictive power of tumor budding in biopsy specimens at the time of diagnosis of locally advanced rectal cancer.…”