DNA-SEQUENCE ANALYSIS OF EXON-2 THROUGH EXON-11 AND IMMUNOHISTOCHEMICAL STAINING ARE REQUIRED TO DETECT ALL KNOWN P53 ALTERATIONS IN HUMAN MALIGNANCIES

p53 mutations are the most common genetic alterations found in human m alignancies, However current estimates of p53 alterations in cancers m ay be inaccurate because there is evidence that current approaches do not detect all p53 alterations, In this study we determine the status of the p53 gene by complete DNA sequencing of exons 2 through 11 as we ll as immunohistochemical staining in cohorts of primary human breast, ovarian and non small cell lung cancer, Overall, 24 of 93 (26%) breas t cancers, 62 of 108 (57%) ovarian cancers and 88 of 154 (57%) non sma ll cell lung cancers contained DNA sequence mutations, whereas positiv e immunohistochemical staining was detected in 15 of 64 (23%) breast, 35 of 94 (37%) ovarian, and 63 of 137 (46%) lung cancers, Of those tum ors that contained mutations, the mutation occurred outside the 'hot-s pot' region in 19% of breast, 18% of ovarian and 17% of lung tumors, i ndicating that a substantial number of mutations remain undetected in studies that are restricted to exons 5 through 9, We observed a high c oncordance between the presence of p53 missense mutations and positive immunohistochemical staining, but a poor concordance between other ty pes of mutations and staining in all three types of malignancies. We c onclude that a combination of DNA sequence analysis of exons 2 through 11 and immunohistochemical staining are required to detect all known alterations in the p53 gene in human malignancies.