Prognostic significance of mitotic rate in localized primary cutaneous melanoma: An analysis of patients in the multi-institutional american joint committee on cancer melanoma staging database

Purpose: The aim of this study was to assess the independent prognostic value of primary tumor mitotic rate compared with other clinical and pathologic features of stages I and II melanoma. Methods: From the American Joint Committee on Cancer (AJCC) melanoma staging database, information was extracted for 13,296 patients with stages I and II disease who had mitotic rate data available. Results Survival times declined as mitotic rate increased. Ten-year survival ranged from 93% for patients whose tumors had 0 mitosis/mm2 to 48% for those with ≥ 20/mm² (P < .001). Mean number of mitoses/mm2 increased as the primary melanomas became thicker (1.0 for melanomas ≤ 1 mm, 3.5 for 1.01 to 2.0 mm, 7.3 for 3.01 to 4.0 mm, and 9.6 for > 8 mm). Ulceration was also associated with a higher mitotic rate; 59% of ulcerated melanomas had ≥ 5 mitoses/mm² compared with 16% of nonulcerated melanomas (P < .001). In a multivariate analysis of 10,233 patients, the independent predictive factors for survival in order of statistical significance were as follows: tumor thickness (χ² = 104.9; P < .001), mitotic rate (χ² = 67.0; P < .001), patient age (χ² = 48.2; P < .001), ulceration (χ² = 46.4; P < .001), anatomic site (χ² = 34.6; P < .001), and patient sex (χ² = 33.9; P < .001). Clark level of invasion was not an independent predictor of survival (χ² = 3.2; P = .37). Conclusion: A high mitotic rate in a primary melanoma is associated with a lower survival probability. Among the independent predictors of melanoma-specific survival, mitotic rate was the strongest prognostic factor after tumor thickness.