Tumor budding activity is an independent prognostic factor in squamous cell carcinoma of the vulva

Tumor budding activity (TBA) is recognized as a potential prognostic factor in carcinomas from several anatomic sites. This study evaluates the prognostic value of TBA in a cohort of squamous cell carcinoma of the vulva (VSCC). TBA, defined as clusters of5 tumor cells that are detached from the main tumor and that infiltrate into surrounding stroma, was assessed in 82 cases of surgically excised VSCC and correlated with patient outcomes. All cases were classified into one of 3 groups: no TBA, low TBA (1-14 foci), and high TBA (≥15 foci). Twenty-three (29.1%), 37 (45.1%), and 22 (26.8%) cases showed no, low, and high TBA, respectively. High TBA was associated with reduced overall survival (OS) on multivariate analysis independent of FIGO stage, human papillomavirus (HPV) status, and p53 status. The majority of tumors with high TBA displayed a p53 mutant staining pattern (77.3%, 17 of 22). The 17 patients whose tumors displayed a p53 mutant/high TBA profile had worse outcomes when compared with 15 patients whose tumors showed a p53 mutant/no TBA or p53 mutant/low TBA profile (mean OS 37.5 versus 63.3 months, respectively, P = .002). High TBA was observed in only 5 of 47 HPV-associated cases, and this subset also seemed to display a worse patient outcome as compared with the rest of the HPV-associated cohort (OS 16.8 versus 142.8 months, P .0001). In summary, these findings indicate that TBA is an independent prognostic indicator in VSCC patients, and that high TBA is associated with worse clinical outcomes.