Prognostic significance of proliferation and motility in primary malignant melanoma of the skin

Abstract

The metastatic cascade depends on the presence of tumor cells which are capable of proliferation as well as of invasion with active motility. In the present study, it was examined whether the demonstration of both features in the primary lesion of malignant melanoma of the skin carries prognostic significance. Proliferation was assessed by mitotic counts and Ki 67 staining, and motility was estimated by image analysis and comparison of the image analysis results with computer simulations; 27 cases of primary malignant melanoma with a maximum vertical tumor thickness exceeding 1 mm were prospectively sampled. Mitotic counts were carried out on H & E stained sections, image analysis of the tumor pattern on S-100 immunostained paraffin slides, and Ki 67 labeling of actively cycling cells was evaluated on frozen sections. Neither proliferation nor pattern analysis alone provided a significant prognostic result with respect to overall survival and to metastasis free survival. The estimates of motility, derived from a combination of pattern analysis and proliferation values, however, proved to be significant predictors of overall survival and metastasis-free survival (log rank test: p less than or equal to 0.05). The motility features were superior to Clark level and Breslow index in this set of cases. The results demonstrate that the assessment of tumor cell proliferation and motility in histological sections may reflect the metastatic potential of primary malignant melanomas of the skin.

Ki67 antigen and PCNA proliferation markers predict survival in anorectal malignant melanoma

“…Two studies reported a correlation between Ki67 staining and survival in thick melanoma (>3 mm and >4 mm) 10,26 . Ki67 was associated with survival in another study 27 and with tumour thickness in other studies 28,29 . Both Ki67 and PCNA, as well as tumour stage and tumour thickness, were correlated with overall survival in a study of 93 cutaneous melanomas 11 .…”

Cell proliferation markers in predicting metastases in malignant melanoma

“…Soyer (14) studied 145 melanocytic tumors aud fouud that within the group of primaiy melanomas there was a significant correlation between proliferative activity as assessed by the expression of Ki-67 antigen and maximum tumor thickness, Clark's level of invasion 'and mitotic rate and possibly with the occurrence of metastasis. Other studies show uo specific association between Ki-67 expression and likelihood of metastasis or survival (15,16). These findings concur with ours, iu which Ki-67 expression was mostly negative iu both metastasizing and non-metastasizing melanomas of comparable thickne.ss and level.…”

Prognostic Factors in Cutaneous Melanoma

“…Proliferation rate is currently often assessed by immunolabeling of Ki-67, which is a nuclear molecule expressed in cells actively transiting the cell division cycle. In one study, quantifi cation of the mitotic rate and immunolabeling of Ki-67, taken in conjunction with a morphological measure of tumor invasiveness, correlated signifi cantly with overall and disease-free survival [ 173 ]. Labeling for either Ki-67 or proliferating cell nuclear antigen (PCNA; another marker for proliferation) has also correlated signifi cantly with disease-free and overall survival by univariate analysis [ 174 ].…”