K-ras gene point mutation in neogenetic lesions of subpleural fibrotic lesions: Either an early genetic event in lung cancer development or a non-specific genetic change during the inflammatory reparative process

In the present study, K-ras mutation was investigated in 156 neogenetic epi thelia that appeared in the lesion of subpleural fibrosis in order to eluci date the close relationship of lung cancer development with pulmonary inter stitial pneumonia. The neogenetic epithelia were histologically subclassifi ed into six types: (i) ciliated bronchial epithelium (CBE); (ii) squamous m etaplastic epithelium (SME); (iii) cuboidal immature epithelium (CIE); (iv) stratified immature epithelium (SIE); (v) mucus cell epithelium (MCE); and (vi) intestinal metaplastic epithelium (IME). K-ras mutation was detected in 9.6% of neogenetic epithelia overall; 21% of CIE, 12% of SIE, 16% of SME , but not in other types of neogenetic epithelia. Immunohistochemically, CI E and SIE frequently expressed surfactant apoprotein and SME was characteri stic to carcinoembryonic antigen expression. According to Ki-67 immunostain , CIE, SIE and SME are likely to grow faster than other histological types of epithelia. K-ras mutation was seen exclusively in codon 12 with predomin ant G to A and G to C substitutions without any G to T transversions, resul ts which are somewhat different to previous studies in lung cancers. The pr esent study dearly demonstrated that K-ras mutation appeared in certain his tological types of neogenetic epithelia, but raised the question of whether K-ras mutation in neogenetic epithelia during the inflammatory reparative process might be an early genetic event in lung carcinogenesis.