Molecular cytogenetic analysis of Bowen's disease and squamous cell carcinoma of the skin by comparative genomic hybridization

Y Yoshikawa MD PhD^a, T Ishida MD^a,b, C Nakamura MD^a, Y Hamamoto MD PhD^a, T Furuya MD^b, S Kawauchi MD PhD^b, A Oga MD PhD^b, M Muto MD PhD^a, K Sasaki MD PhD^b

^aDepartment of Dermatology and Biomolecular Recognition, ^bDepartment of Pathology; Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan

AIM : Bowen's disease and squamous cell carcinoma (SCC) of the skin are both keratinocyte-derived malignant tumors. Although Bowen's disease is referred to as "SCC in situ" in some textbooks, the clinical characteristics as well as the histopathological features of Bowen's disease are clearly different from those of SCC. It is still controversial whether Bowen's disease is an early lesion of SCC and the genetic differences between Bowen's disease and SCC have not yet been clearly described. In this study, in order to elucidate the genetic aberrations underlying the pathological and biological differences between Bowen's disease and SCC, we examined DNA sequence copy number aberrations (DSCNAs) in these disorders. METHODS : High-molecular-weight DNA extracted from fresh-frozen tissue specimens of 10 Bowen's disease and 11 SCC patients was analyzed for DSCNAs using comparative genomic hybridization (CGH). Of SCC specimens, 7 of them were classified as stage I and the reminder as stage II, according to the TNM staging system. CGH was performed by standard techniques and the results were analyzed statistically. RESULTS : In Bowen's disease, CGH analysis revealed gains (including amplification) in chromosomes 1q22-q31, 7q21.3-q31.3, 20p, Xq23-qter, 1p35-p32.1, 1p31.1-p21, 1q32.1-q43, 3q22-qter, 8q23-qter, and 20q ( > 50% ). Copy number decreases were observed on chromosomes 17p, 2q21,1-q24.3, 16q, 17q, 5q21-q23, and 2q31-qter ( > 40% ). In SCC, gains (including amplification) were detected at chromosomes 3q, 8q,21.3-qter, 7q31.3, and 5p ( > 36% ). Losses were detected at chromosomes 3pter-p21.2, 5q11.2-q23.3, 17p, 8p, and 9pter-p21 ( > 36% ). Gains of 1p31.1-p21 (p < 0.02), 1q22-q31 (p < 0.03), 1q32.1-q43 (p < 0.02) and Xq23-qter (p < 0.004) were preferentially detected in Bowen's disease. Loss of 2q21.1-q24.3 were observed only in Bowen's disease (p < 0.004). Loss of 3pter-p21.2 was found exclusively in SCC (p < 0.001). CONCLUSIONS : DSCNAs common to Bowen's disease and SCC were gains of 3q and 8q, and loss of 17p. These observations suggest that these chromosomes sites harbor the potential genes involved in the tumorigenesis of skin cancer. However, there was significant difference in chromosomal regions with DSCNAs between Bowen's disease and SCC. These findings indicate that Bowen's disease differs from SCC at the cytogenetic level, and that Bowen's disease and SCC in situ might be different disorders.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 796 (Genetic instability).