Intratumoral budding: A novel prognostic biomarker for tumor recurrence and a potential predictor of nodal metastasis in uterine cervical cancer.

Objective: To evaluate the prognostic and predictive significance of lymphovascular invasion (LVI) and lymph node metastasis of intratumoral budding (ITB) and its correlation with clinicopathological parameters in patients with cervical cancer.

Methods: Total 151 patients with cervical cancer who underwent radical hysterectomy with pelvic and/or paraaortic lymphadenectomy were included. We assessed the status of ITB and peritumoral budding (PTB) in all available hematoxylin and eosin-stained specimens. Univariate and multivariate analyses were performed for ITB, PTB, and other clincopathological parameters as predictors of recurrence.

Results: ITB (≥3TB/HPF) was significantly associated with large tumor size, deep stromal invasion, LVI, parametrial invasion, and lymph node metastasis. The numbers of ITBs and PTBs were positively correlated (r = 0.754, p < 0.0001). ITB was more frequently observed in squamous cell carcinoma compared with adenocarcinoma and adenosquamous cell carcinoma (p = 0.010). ITB was found to be an independent prognostic factor for tumor recurrence by multivariate analysis (hazard ratio, 1.92; 95% confidence interval [CI], 1.37-9.90; p = 0.026). Multiple logistic regression showed association of LVI (odds ratio [OR], 1.85; 95% CI, 1.11-3.06; p = 0.017) and lymph node metastasis (OR, 1.96; 95% CI, 1.26-4.66; p = 0.019).

Conclusion: ITB is an independent prognostic factor for tumor recurrence. ITB is a surrogate marker for predicting LVI in cervical cancers. The evaluation of ITB may be readily applied in the clinical setting for improved prognosis and to guide the clinical management of patients with cervical cancer.