Minichromosome maintenance proteins are useful adjuncts to differentiate between benign and malignant melanocytic skin lesions

• Published in: Journal of the American Academy of Dermatology 2009-05, Vol.60 (5), p.808-813
• Main Authors: Gambichler, Thilo, MD, Shtern, Marina, MD, Rotterdam, Sebastian, MD, Bechara, Falk G., MD, Stücker, Markus, MD, Altmeyer, Peter, MD, Kreuter, Alexander, MD
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; biomarkers; Biomarkers, Tumor - analysis; Cell Cycle Proteins - analysis; cell cycle regulators; Dermatology; DNA-Binding Proteins - analysis; Dysplastic Nevus Syndrome - metabolism; Female; Humans; Immunohistochemistry; Ki-67 Antigen - analysis; Male; malignant melanoma; Medical sciences; melanocytic nevus; MIB-1; Middle Aged; Minichromosome Maintenance Complex Component 3; Minichromosome Maintenance Complex Component 4; Minichromosome Maintenance Complex Component 7; minichromosome maintenance protein; Nevus, Pigmented - chemistry; Nuclear Proteins - analysis; proliferation; Skin Neoplasms - chemistry
• ISSN: 0190-9622; 1097-6787
• DOI: 10.1016/j.jaad.2009.01.028

Background Markers identifying premalignant and malignant melanocytic skin lesions are needed. Objective We aimed to investigate the protein expression of minichromosome maintenance (MCM) proteins in melanocytic skin lesions with different malignant potential. Methods Paraffin-embedded sections of benign melanocytic nevi (BN, n = 37), dysplastic nevi (DN, n = 25), and primary superficial spreading (SSM, n = 58) were assessed. Immunohistochemistry was performed for Ki-67, MCM3, MCM4, and MCM7 antibodies. Results Ki-67 expression of SSM was significantly increased when compared to DN ( P = .0001) and BN ( P = .0015). Compared to BN and DN, expression of MCM3 was significantly increased in SSM ( P < .0001 and P = .019, respectively). MCM3 expression of DN was significantly increased as compared to BN ( P = .0067). There was a significant correlation between MCM3 expression and Breslow tumor thickness ( r = 0.44, P = .019). In SSM, MCM4 expression was significantly increased when compared with DN ( P < .0001) and BN ( P = .0033). MCM4 immunoreactivity was significantly higher in DN than in BN ( P = .016). Immunohistology of MCM7 did not reveal significant differences between the groups investigated ( P = .48). However, immunoreactivity of MCM7 significantly correlated with Breslow tumor thickness and Clark level ( r = 0.39, P = .023; r = 0.44, P = .010, respectively). Limitations Limitations of our study include the absence of survival data, mRNA results, and functional studies. Conclusions MCM3 as well as MCM4 are differentially expressed in BN, DN, and SSM. Hence, immunolabeling of MCM3 and MCM4 proteins appears to be a promising additive tool for distinguishing benign from malignant melanocytic skin lesions.