title: Differential expressions of cyclin-dependent kinase inhibitors (p27 and p21) and their relation to p53 and Ki-67 in oral squamous tumorigenesis.
abstract: The cyclin-dependent kinase inhibitors p27Kip1 and p21WAF1/Cip1 play important roles in cell-cycle regulation. Although alterations of these genes have been linked to tumorigenesis of several human carcinomas, their involvement in head and neck squamous tumorigenesis is rarely investigated. To determine the role of these genes in the evolution of squamous carcinoma of the head and neck we evaluated their protein expression by immunohistochemistry in non-dysplastic squamous epithelium, premalignant lesions and oral squamous carcinomas. The p53 gene and Ki-67 expressions were correlated with traditional clinicopathologic variables. Our study shows that in histologically non-dysplastic squamous epithelium, p27 expression was noted mainly in superficial differentiated cells, whereas p21, p53 and Ki-67 staining was observed in basal and suprabasal cells. In dysplasia, divergent expression between p27 and p21 was observed: p27 precipitously decreased and p21, p53, and Ki-67 increased with histologic progression. In squamous carcinomas, p27 was mainly expressed in well differentiated tumor cell nests, while the expressions of p21, p53, and Ki-67 were variable in the poorly differentiated tumor areas. A significant inverse relationship between p27 expression and those of p21, p53, and Ki-67 was observed, but no significant association between any of these markers and clinicopathologic factors was noted in this cohort. Our study indicates that: i) down-regulation of p27 and up-regulation of p21 are associated with early progression of HNSC, ii) p21 expression correlates positively with proliferation while p27 correlates positively with cell differentiation and iii) concurrent p27 and p21 expression analysis may allow for better assessment of HNSC progression.
authors.affiliation: Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hong-Ran
authors.initials: HR
authors.lastname: Choi
authors.forename: Susan A
authors.initials: SA
authors.lastname: Tucker
authors.forename: Zheng
authors.initials: Z
authors.lastname: Huang
authors.forename: Ann M
authors.initials: AM
authors.lastname: Gillenwater
authors.forename: Mario A
authors.initials: MA
authors.lastname: Luna
authors.forename: John G
authors.initials: JG
authors.lastname: Batsakis
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000737:chemistry; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D018450:Disease Progression; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D016158:Genes, p53; D005887:Gingival Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis* / Q000235:genetics; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27