High tumor budding stratifies breast cancer with metastatic properties

Abstract

Tumor budding refers to single or small cluster of tumor cells detached from the main tumor mass. In colon cancer high tumor budding is associated with positive lymph nodes and worse prognosis. Therefore, we investigated the value of tumor budding as a predictive feature of lymph node status in breast cancer (BC). Whole tissue sections from 148 surgical resection specimens (SRS) and 99 matched preoperative core biopsies (CB) with invasive BC of no special type were analyzed on one slide stained with pan-cytokeratin. In SRS, the total number of intratumoral (ITB) and peripheral tumor buds (PTB) in ten high-power fields (HPF) were counted. A bud was defined as a single tumor cell or a cluster of up to five tumor cells. High tumor budding equated to scores averaging >4 tumor buds across 10HPFs. In CB high tumor budding was defined as ≥10 buds/HPF. The results were correlated with pathological parameters. In SRS high PTB stratified BC with lymph node metastases (p ≤ 0.03) and lymphatic invasion (p ≤ 0.015). In CB high tumor budding was significantly (p = 0.0063) associated with venous invasion. Pathologists are able, based on morphology, to categorize BC into a high and low risk groups based in part on lymph node status. This risk assessment can be easily performed during routine diagnostics and it is time and cost effective. These results suggest that high PTB is associated with loco-regional metastasis, highlighting the possibility that this tumor feature may help in therapeutic decision-making.

High-Grade Tumor Budding Stratifies Early-Stage Cervical Cancer with Recurrence Risk

“…These findings suggest that tumor budding is a frequent early event of cervical cancer dissemination and is associated with cervical cancer progression. Similar results have been demonstrated in colorectal carcinoma [21, 26], breast cancer [16], and gastric cancer [27]. The budding cells at the invasive tumor front are considered epithelial mesenchymal transition (EMT)-derived tumor cells, with increased migratory and invasive capacities and stem cell properties [21, 28, 29].…”

“…Morphologically, tumor budding is defined as the presence of single tumor cells or isolated small clusters of tumor cells (up to 5 tumor cells) scattered in the stroma at the invasive front; it represents a type of local diffusely infiltrative growth and occurs when tumor cells detach from the invasive tumor margin and migrate into the surrounding stroma. Tumor budding has frequently been observed in several types of solid tumors, including colorectal cancer [12], esophageal carcinoma [13], pancreatic carcinoma [14, 15], breast cancer [16, 17], lung carcinoma [18, 19], and endometrial carcinoma [20]; tumor budding has been recognized as an aggressive indicator and an adverse prognostic factor [12–20]. Moreover, as a result of its significant prognostic value, tumor budding is recommended by the International Union against Cancer for inclusion in the pathological report of colorectal cancer as an additional prognostic factor [21].…”

Does evaluation of tumour budding in diagnostic biopsies have a clinical relevance? A systematic review

“…The studies evaluated tumour budding in pretreatment samples in the following cancers: five studies (four cohorts) on rectal cancer, two on colorectal cancer and three (two cohorts) on oral cancer . There was one study on breast cancer, one on epidermoid anal cancer and one on cancer of the external auditory canal …”

“…Pre‐operative tumour budding in oral cancer also had strong correlations with tumour grade, tumour depth and blood vessel invasion . In breast cancer, tumour budding is associated with venous invasion . A study of epidermoid anal cancer revealed that pretreatment tumour budding was a significant predictor of overall survival .…”

“…In addition, some of these studies reported the concordance of the score of tumour budding in pre‐operative diagnostic biopsy samples and postoperative surgical specimens . However, the implementation of tumour budding for pathology reports and treatment planning still requires further studies …”