p53, p21, Rb, and MDM2 proteins in tongue carcinoma from patients <35 versus >75 years

Abstract

Relatively rare squamous cell carcinomas of the tongue in young patients may be associated with different etiologic factors and pathogenetic mechanisms than carcinomas from the same site in older patients. Alterations in cell cycle proteins likely contribute to the biologic behavior of these neoplasms. The purpose of this investigation was to evaluate cell cycle proteins (p53, p21, Rb, MDM2) in lateral tongue cancers from patients at the two ends of the age spectrum. All available archived lateral tongue carcinomas from patients <35 years (n = 36, 23 males and 13 females) were sectioned, immunohistochemically stained, and evaluated. Protein expression was scored as percent positive nuclei. An equal number of sequentially accessioned lateral tongue specimens from patients >75 years (23 males and 13 females) were stained and compared. Positive p53 staining was seen in 18/36 of the <35-year group versus 24/36 of the >75-year group (p = 0.149). Increased p21 staining (both percent of positive cells and intensity) was evident in 25/32 of the <35-year group versus 24/32 of the >75-year group (p = 1.0). Increased p21 expression was seen in both p53-positive and -negative cases in both age groups. Rb protein was increased in 16/29 of the <35-year group versus 17/26 of the >75-year group (p = 0.58). Fourteen cases (4/35 vs 10/36, p = 0.135) showed positive MDM2 staining; MDM2-positive cases were also p53 positive in 4/4 younger and 8/10 older patients. We conclude that p53, p21, Rb, and MDM2 are over-expressed in lateral tongue cancers, and that immunohistochemical profiles are heterogeneous. A p53-independent pathway of p21 induction is supported by the results; p53 suppression may be associated with MDM2 protein expression in a subset of cancers. Significant differences in the expression of p53, p21, Rb, and MDM2 proteins are not evident in lateral tongue carcinomas from patients <35 years as compared to patients >75 years.