Abstract | BACKGROUND:
Tumor 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. METHODS: 202 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. RESULTS: Increased 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. CONCLUSIONS: Ki-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.
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Authors | Rita G Ladstein, Ingeborg M Bachmann, Oddbjørn Straume, Lars A Akslen |
Journal | BMC cancer
(BMC Cancer)
Vol. 10
Pg. 140
(Apr 14 2010)
ISSN: 1471-2407 [Electronic] England |
PMID | 20398247
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers, Tumor
- Cell Cycle Proteins
- Chromosomal Proteins, Non-Histone
- DNA-Binding Proteins
- Histones
- Ki-67 Antigen
- Microfilament Proteins
- Nuclear Proteins
- centromere protein F
- MCM4 protein, human
- Minichromosome Maintenance Complex Component 4
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Topics |
- Aged
- Biomarkers, Tumor
(analysis)
- Cell Cycle Proteins
(analysis)
- Cell Proliferation
- Chi-Square Distribution
- Chromosomal Proteins, Non-Histone
(analysis)
- DNA-Binding Proteins
(analysis)
- Histones
(analysis)
- Humans
- Immunohistochemistry
- Kaplan-Meier Estimate
- Ki-67 Antigen
(analysis)
- Melanoma
(chemistry, mortality, pathology)
- Microfilament Proteins
(analysis)
- Middle Aged
- Minichromosome Maintenance Complex Component 4
- Mitotic Index
- Necrosis
- Neoplasm Invasiveness
- Neoplasm Staging
- Nuclear Proteins
(analysis)
- Phosphorylation
- Predictive Value of Tests
- Prognosis
- Proportional Hazards Models
- Skin Neoplasms
(chemistry, mortality, pathology)
- Tissue Array Analysis
- Up-Regulation
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