P53 Gene Mutations in Pituitary Carcinomas

Abstract

Although p53 overexpression detected by immunohistochemistry has been reported in pituitary adenomas and carcinomas, genetic mutations in the p53 gene have not been previously detected in these tumors. We analyzed a series of eight pituitary adenomas and six pituitary carcinomas by immunohistochemistry, polymerase chain reaction amplification, and sequencing of p53 exon 5 through exon 8 for genetic mutations. Three carcinomas showed more than 20% expression of p53 protein in the tumor cells. One of these tumors with 60% overexpression of p53 protein had a mutation in codon 248, a common "hot spot" for p53 mutation, while the other carcinoma with 90% overexpression of p53 protein had a mutation in codon 135. All adenomas were negative for p53 mutations and had 15% of the cells expressing the p53 protein. Analysis of control tumors including four lung carcinomas with proven p53 mutations also had greater than 85% of the tumor cells overexpressing p53 protein. Two breast carcinoma cell lines with known p53 mutations, MBA-MD 231 and MBA-MD-486, also showed greater than 85% of the tumor cells overexpressing p53. These results show that p53 mutations are present in a subset of pituitary carcinomas and are usually associated with a high percentage of tumor cells overexpressing the p53 protein.

The role of proto-oncogene GLI1 in pituitary adenoma formation and cell survival regulation

“…Whereas p53 is usually undetectable in healthy cells due to rapid degradation, mutations in the TP53 gene can lead to overexpression of oncogenic p53 in cancer cells (Janicke et al 2008). Because TP53 mutations have only rarely been detected in pituitary adenomas, mutationrelated p53 upregulation seems not very feasible (Suliman et al 2001, Tanizaki et al 2007). However, oxidative stress is a general feature of cancer cells, going along with DNA damages and apoptosis.…”

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“…Mutations in proto-oncogenes like KRAS, RET, PTTG and c-MYC and in tumor suppressors like RB1 are very rarely reported in corticotrophinomas (10). Mutations in the p53 gene (TP53) are extremely rare and were found only in atypical corticotroph (i.e., aggressive) tumors and carcinomas (11,12). CD is rarely seen in the context of genetic syndromes like multiple endocrine neoplasia MEN1 (MEN1 encoding menin), MEN4 (CDKN1B encoding p27/KIP1), McCuneAlbright syndrome (GNAS oncogene encoding the stimulatory G protein Gsa) and never in Carney complex (PRKAR1A) (13,14,15).…”

The Role of p16 and MDM2 Gene Polymorphisms in Prolactinoma: MDM2 Gene Polymorphisms May Be Associated with Tumor Shrinkage

“…Based on this hypothesis, MDM2 protein expression in hypophyseal tumors was first demonstrated in a study by Suliman et al (19). Although p53 is one of the most frequently inactivated genes in human cancer, p53 mutation was very rarely detected in hypophyseal adenomas (34,35). As a possible explanation for this, it was suggested that in the pathogenesis of hypophyseal tumors, the effect of cellular stress on p53 pathway could be more important than mutations in p53 and that p53 may not initiate tumor development, but could play a role in prognosis (36).…”