Prognostic Value of Tumor Budding in Early-Stage Cervical Adenocarcinomas

Background: Tumor budding has recently been reported as an independent adverse prognostic factor for colorectal adenocarcinomas and other types of carcinoma in the digestive tract. This study aimed to evaluate the prognostic value of tumor budding in patients with early-stage cervical adenocarcinomas and any associations with other clinical and pathological features. Methods: Histological slides of patients with early-stage (IB-IIA) usual-type endocervical adenocarcinoma who underwent radical hysterectomy and pelvic lymph node dissection, without preoperative chemotherapy, between January 2006 and December 2012 were reviewed. Tumor budding was evaluated in routinely-stained sections and defined as detached single cells or clusters of fewer than 5 cells in a tumor invasive front and was stratified based on the number of bud counts in 10-high-power fields as low (<15 buds) and high (≥15 buds). Correlations between tumor bud count and other clinical and pathological variables including follow-up outcomes were assessed. Results: Of 129 patients, a high tumor bud count was observed in 15 (11.6%), positively associated with histologic grade 3 (p<0.001), invasive pattern C (Silva System) (p=0.004), lymph node metastasis (p=0.008), stage IB2-IIA (p=0.016), and tumor size >2 cm (p=0.036). Kaplan-Meyer analysis showed a significant decrease in both disease-free survival and cancer-specific survival for patients with a high tumor bud count (p=0.027 and 0.031, respectively). On multivariate analysis, histologic grade 3 was the only independent predictor for decreased disease-free survival (p=0.004) and cancer-specific survival (p=0.003). Conclusions: A high tumor budding count based on assessment of routinely-stained sections was found to be associated with decreased disease-free and cancer-specific survival in patients with early-stage cervical adenocarcinomas. However, it was not found to be an independent prognostic predictor in this study.