engleski

The relevance of p53 isoforms for the prognosis and outcome in soft tissue sarcoma

Soft tissue sarcoma (STS) encompasses a plenitude of malignant tumors of the connective tissue. Most of these tumors are very invasive and the response to chemotherapy and radiation is very limited. The mechanism of soft tissue sarcoma tumorigenesis is still unclear ; therefore, they represent a major therapeutic challenge. Mutation of p53 is a common hallmark of cancer. It is mutated in more than 50% of human tumors. However, knowledge about the prognostic relevance of p53 mutations in STS is not comprehensive, and, according to our data, seems to be rare. Therefore, other mechanisms of p53 inactivation might be involved. As is already well accepted, p53 is expressed not only as full length, but also as isoforms, some of which inhibit wild-type p53. There are no studies that have examined the relative expression of p53 isoforms in STS so far. Here, we have analyzed the relative mRNA expression of the p53, Δ40p53, Δ133p53 (C- terminal isoforms), p53α, p53β and p53γ (N- terminal isoforms) in a panel of 5 STS cell lines, 26 STS specimens and 15 matched normal adjacent tissues using real-time PCR. Further we have analyzed their relationship to the outcome of disease. We have found that almost all isoforms were expressed equally, only p53γ was expressed at a higher level compared to p53. Further, we have observed that all three N-terminal isoforms are positively correlated to each other, compared to C-terminal ones which were not correlated. Additionally, higher p53β expression was significantly associated with longer overall survival (OS) of patients, while there was a trend toward significant association of higher Δ40p53 expression with longer OS. However, the higher Δ40p53 expression was positively correlated to reappearance of tumor with marginal statistical significance. These results have shown the implications of p53 isoforms in development of STS and might provide the elucidation for deregulated p53 function in STS.

p53 isoforms; soft tissue sarcoma

nije evidentirano