Nuclear morphometry, immunohistochemical staining with Ki‐67 antibody and mitotic index in the assessment of proliferative activity and prognosis of primary malignant melanomas of the skin

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Abstract
Nuclear morphometry, immunohistochemical staining with Ki-67 antibody and mitotic index were studied in primary cutaneous malignant melanomas. The number of Ki-67 positive cells/ 200 tumor cells did not correlate with any nuclear morphometrical parameters, and it only approached but did not reach significant correlation with melanoma thickness according to Breslow. The nuclear area, short axis and long axis correlated with melanoma thickness, but the nuclear axis ratio (which reflects the sphericity of nuclei) and melanoma thickness did not show significant correlation. Mitotic index was higher in thick melanomas and in melanomas with high Ki-67 positivity, large nuclear area, long nuclear short axis, and small nuclear axis ratio. In Cox's stepwise proportional hazard model, melanoma thickness and the nuclear axis ratio were significant independent prognostic factors for patient survival, while the nuclear area, short axis and long axis, gender, age, Clark level, mitotic index and Ki-67 positivity lacked significant independent prognostic value. The results suggest that the proliferative activity of tumor cells does not alone explain the great importance of tumor thickness as prognosticator in melanoma. The thickness of melanoma measured according to Breslow and the nuclear axis ratio are more efficient prognosticators in melanoma than parameters associated with proliferation.