Role of 17p13.3 chromosomal region in determining p53 protein immunopositivity in human astrocytic tumors

Abstract

Immunohistochemistry of p53 protein is being increasingly performed as a clinical service as well as in research for prediction of tumor behavior. Although early reports suggested that p53 immunopositivity was associated with p53 gene alterations, recent evidence indicates that this is not always true. Earlier, we had demonstrated the significant association of loss of heterozygosity (LOH) of the chromosomal region 17p13.3 with higher grades of human astrocytic tumors. This was independent of the heterozygosity status of p53. LOH of p53 was taken as an indicator of p53 gene alteration, which was substantiated by sequencing a subset of the tumors. In the present study, we report that p53 immunopositivity in 40 of the same set of tumors (five could not be evaluated because of paucity of tissue) was significantly associated with LOH of 17p13.3 region (Fisher's exact two-tailed, P=0.012; odds ratio, 12) but not with LOH of p53 (Fisher's exact two-tailed, P=0.324; odds ratio, 2.24). This indicates that the gene(s) on the 17p13.3 region of the human chromosome may be influencing the p53 immunopositivity status of glial tumors and possibly other tumors in general. This has great implications in interpreting p53 immunohistochemistry results of biopsies of various tumor types as due to p53 mutations alone. The study thus points to a new molecular correlate for p53 immuno-positivity in tumors.