GENDER COMPARISONS IN HUMAN LUNG-CANCER - ANALYSIS OF P53 MUTATIONS, ANTI-P53 SERUM ANTIBODIES AND C-ERBB-2 EXPRESSION

Little is known about the molecular mechanisms of lung carcinogenesis in women. We initiated an investigation of the role of gender in pulmo nary carcinogenesis by analysis of p53 mutations, immunohistochemistry , serum antibodies and c-erbB-2 expression in a series of 63 male and 44 female lung cancer patients whose tumors were resected at the Mayo Clinic between 1991 and 1992. There were 102 smokers and 5 never smoke d. Adenocarcinoma was the more frequent histological type in women (62 %) than in men (41%). Sequence analysis of exons 5-8 in 42 females and 49 males identified 44 p53 mutations in 42 tumors (46%). Base substit ution mutations showed a preponderance of G:C-->T:A transversions, whi ch were more frequent in women than men (40 versus 25%) and in individ uals exposed to asbestos, c-erbB-2 immunohistochemical staining was id entified more frequently in females (nine cases) than males (two cases ). Marked immunohistochemical staining for p53 positively correlated w ith the presence of missense mutations in exons 5-8 (81%, P < 0.001). Seven missense mutations (four in exon 5, two in exon 6, one in exon 8 ) were identified in five of nine patients who had serum antibodies re cognizing p53; tumors from these patients were also strongly positive for p53 by immunohistochemistry. These and other results indicate gend er differences in the genetic and biochemical alterations in lung canc er and generate hypotheses regarding; gender differences in lung cance r susceptibility.