Correlation between tumor budding and post-resection prognosis in patients with invasive squamous cell carcinoma of the thoracic esophagus.

Background: Tumor budding is defined as an isolated single cancer cell or a cluster of cancer cells composed of fewer than five cells at the invasive front of a tumor. The aim of the present study was to identify correlations between tumor budding and clinicopathological factors and their impact on postoperative prognosis in invasive squamous cell carcinoma of the thoracic esophagus.

Methods: The subjects were 82 patients who underwent curative resection. The number of tumors showing budding was counted immunohistochemically based on positivity for cytokeratin (AE1/AE3) to distinguish cancer cells from inflammatory cells, and the patients were divided into low-grade and high-grade budding groups. High-grade budding was defined as ≥5 budding foci per field under a 20× objective lens.

Results: One group of 36 patients (43.9%) and a second group of 46 patients (56.1%) were classified into the low-grade and high-grade budding groups, respectively. Patients in the high-grade budding group had significantly larger tumor size, deeper depth of invasion, more frequent lymphatic invasion and venous invasion, as well as more lymph node metastases, than those in the low-grade budding group. Disease-free and overall survivals were worse in the high-grade budding group than in the low-grade budding group (P<0.0001 and P=0.0002, respectively). Three of four patients who had tumor recurrence more than 5 years postoperatively belonged to the low-grade budding group.

Conclusions: Tumor budding appears to be an indicator of tumor growth and invasiveness. Patients with low-grade budding are likely to have a better prognosis than those with high-grade budding, but the tumor may recur in the late phase postoperatively in patients with low-grade budding.