Mitotic rate correlates with sentinel lymph node status and outcome in cutaneous melanoma greater than 1 millimeter in thickness: A multi-institutional study of 1524 cases

Background: The 7th edition of the TNM American Joint Committee on Cancer classification incorporates mitotic rate (MR) only for primary cutaneous melanoma (PCM) with Breslow thickness (BT) <= 1 mm. Objective: To investigate whether and to what extent MR is able to predict sentinel lymph node (SLN) status and clinical outcome of PCM patients with BT >1 mm. Methods: The study included consecutive patients with PCM. Logistic regression and Cox regression model were used to analyze the impact of MR on SLN status, disease- free survival (DFS), and overall survival. Results: From 1998 to 2015, 1524 PCM (median age 57.8 years) cases were diagnosed with a BT >1 mm in six centers of the Italian Melanoma Intergroup. Median follow-up was 5.0 years. By multivariate analysis, MR was associated with SLN positivity (odds ratio 1.98, 95% confidence interval [CI] 1.12-3.50, P = .018). After adjusting for BT, ulceration, age, sex, and SLN status, MR correlated with a poor DFS (hazard ratio 1.52, 95% CI 1.18-1.97, P = .002) and overall survival (hazard ratio 1.63, 95% CI 1.17-2.29, P = .004). Limitations: Retrospective analysis. Conclusion: MR is an independent prognostic factor for PCM patients with BT >1 mm. Incorporating this tissue biomarker could provide a better stratification of patients entering clinical trials in the adjuvant setting.