P53 GENE STATUS IN ENDOMETRIAL CARCINOMAS SHOWING DIFFUSE POSITIVITY FOR P53 PROTEIN BY IMMUNOHISTOCHEMICAL ANALYSIS

Although detection of p53 protein by immunohistochemical testing was o riginally thought to indicate p53 gene mutation, recent analyses of hu man malignancies have shown that high expression of p53 protein may oc cur without detectable gene mutation. Several explanations have been p roposed for this phenomenon, including mutation out of ''hot spot'' re gions, overexpression of wild-type protein, sampling error in molecula r analyses, and conformational changes of wild-type p53 protein. As di scussed, it is unlikely that the first two possibilities contribute si gnificantly to the occurrence of this phenomenon, and the current stud y examined the possibility that sampling error in molecular analyses m ight account for a lack of concordance between immunohistochemical and molecular analyses. Such a possibility exists because immunohistochem ical studies frequently report high expression when staining is only f ocal or regional and molecular analyses are based on the polymerase ch ain reaction, which is highly exponential in nature and may not detect mutation if the target gene segment is not amplified early in the cha in reaction. In the current report, p53 protein expression was examine d by immunohistochemical testing in 45 cases of endometrioid carcinoma , and all cases showing diffuse positivity were then examined by polym erase chain reaction in combination with single-strand conformational analysis for exons 4 to 9 with the use of a microdissection technique to separate malignant from benign cells. Of the 45 cases, diffuse stai ning was found in four cases, and only two of the four were found to s how evidence of gene mutation. This study concluded that high p53 prot ein expression can occur without evidence of gene mutation in endometr ial carcinoma; because all four cases examined by polymerase chain rea ction with single-strand conformational analysis in this study showed diffuse staining by immunohistochemical analysis, it seems unlikely th at sampling error in molecular analysis accounts for the lack of conco rdance. As discussed, it seems distinctly possible that conformational changes of the p53 wild-type protein account for this phenomenon. Fur ther investigation into this possibility might be beneficial.