CDC28 protein kinase regulatory subunit 1B (CKS1B) expression and genetic status analysis in oral squamous cell carcinoma
Gemma Martín-Ezquerra1*, Rocío Salgado2*, Agustí Toll1, Teresa Baró2, Sergi Mojal4, Mireia Yébenes5, Mª Pilar Garcia-Muret3, Francesc Solé2, Francesc Alameda Quitllet2, Blanca Espinet2^ and Ramon M. Pujol1^
1Department of Medicine and Dermatology, Universitat Autònoma de Barcelona, Hospital del Mar, Barcelona, Spain, 2Molecular Cytogenetics Laboratory, Department of Pathology, IMIM-Hospital del Mar, GRETNHE, IMIM, Barcelona, Spain, 3Department of Dermatology. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, 4Assessorament Metodològic en Investigació Biomèdica (AMIB)-IMIM, Barcelona, Spain and 5Department of Dermatology, Consorci Sanitari Parc Taulí, Sabadell, Spain
*These two authors contributed equally to this work.
^These senior authors equally contributed to this study.
Offprint requests to: Gemma Martin-Ezquerra, M.D., Department of Dermatology, Hospital del Mar, IMAS, Passeig Marítim, 25-29, 08003 Barcelona, Spain. e-mail: GMartin@hospitaldelmar.cat
Summary. CKS1B is a member of the highly conserved cyclin kinase subunit 1 (CKS1) protein family which interacts with cyclin-dependent kinases and plays a critical role in cell cycle progression. In oral squamous cell carcinoma (OSCC), as in other malignancies, CKS1B overexpression has been correlated with reduced survival. To our knowledge, no studies evaluating the genetic status of CKS1B gene in OSCC have been reported. Herein, genetic and protein status of CKS1B were analyzed by immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) techniques in a series of primary OSCC (n=51) and lymph node OSCC metastases samples (n=14). The observed results were compared with those obtained in either inflammatory (oral lichen planus [OLP]) (n=13) and premalignant oral mucosal lesions (oral leukoplakia) (n=16). A significant CKS1B overexpression was observed in OSCC and lymph node metastases samples than in OLP and oral leukoplakia (mean 70% vs 35%, p<0.001). CKS1B overexpression correlated with p27 loss of expression (p=0.0013) and SKP2 overexpression (p<0.00). FISH study disclosed statistical differences in both gene amplifications and gains between samples corresponding to OSCC and metastases from those of OLP and leukoplakia (p<0.001). Amplifications were present in 53% of OSCC samples and 33% of lymph node metastases vs 14% of oral leukoplakia and 0% of
OLP biopsy specimens (p=0.002). Polysomies of chromosome 1 were seen in 46% of OSCC, 33% of ganglionar metastases, 14% of oral leukoplakia and 10% of OLP (p=0.036). Correlation of CKS1B over-expression and gains (both polysomies and amplifications) determined by FISH was statistically significant (p<0.001).
Our results indicate that a high CKS1B expression is a common finding in primary OSCC which correlates with p27 low expression and SKP2 overexpression. This phenomenon may be due either to numerical (chromosome 1 polysomy) or structural (amplifications) CKS1B genetic abnormalities. This phenotypical and cytogenetic profile is not observed in premalignant or inflammatory oral mucosal lesions. Histol Histopathol 26, 71-77 (2011)
Key words: Carcinogenesis, p27, CKS1B, FISH, Squamous cell carcinoma, Oral leukoplakia, Lichen planus
DOI: 10.14670/HH-26.71