Abstract
BackgroundTumor cell proliferation is a predictor of survival in cutaneous melanoma. The aim of the present study was to evaluate the prognostic impact of mitotic count, Ki-67 expression and novel proliferation markers phosphohistone H3 (PHH3), minichromosome maintenance protein 4 (MCM4) and mitosin, and to compare the results with histopathological variables.Methods202 consecutive cases of nodular cutaneous melanoma were initially included. Mitotic count (mitosis per mm2) was assessed on H&E sections, and Ki-67 expression was estimated by immunohistochemistry on standard sections. PHH3, MCM4 and mitosin were examined by staining of tissue microarrays (TMA) sections.ResultsIncreased mitotic count and elevated Ki-67 expression were strongly associated with increased tumor thickness, presence of ulceration and tumor necrosis. Furthermore, high mitotic count and elevated Ki-67 expression were also associated with Clark's level of invasion and presence of vascular invasion. High expression of PHH3 and MCM4 was correlated with high mitotic count, elevated Ki-67 expression and tumor ulceration, and increased PHH3 frequencies were associated with tumor thickness and presence of tumor necrosis. Univariate analyses showed a worse outcome in cases with elevated Ki-67 expression and high mitotic count, whereas PHH3, MCM4 and mitosin were not significant. Tumor cell proliferation by Ki-67 had significant prognostic impact by multivariate analysis.ConclusionsKi-67 was a stronger and more robust prognostic indicator than mitotic count in this series of nodular melanoma. PHH3, MCM4 and mitosin did not predict patient survival.
Highlights
Tumor cell proliferation is a predictor of survival in cutaneous melanoma
Increased mitotic count was strongly associated with tumor thickness, presence of ulceration and tumor necrosis, as well as advanced Clark's level of invasion (p = 0.038) and presence of vascular invasion (p = 0.052) (Table 1)
Elevated Ki-67 expression was correlated with increased tumor thickness and presence of tumor ulceration, tumor necrosis (p = 0.007), increased Clark's level of invasion (p = 0.015) and vascular invasion (p = 0.027) (Table 1)
Summary
Tumor cell proliferation is a predictor of survival in cutaneous melanoma. Cutaneous melanoma is one of the most rapidly increasing malignancies among Caucasians [1,2], and improved understanding of its biological characteristics and prognostic factors is important. Since tumor cell proliferation is an increasingly important prognostic factor in many. The 2002 American Joint Committee on Cancer (AJCC) staging system for melanoma was based on a multicenter analysis of prognostic factors in more than 17,000 patients [4]. Mitotic frequency is a powerful predictor of survival [6,7,8,9,10,11], and the inclusion of this marker in staging of primary melanomas has been included in the 2010 edition of the AJCC pTNM staging system.
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