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 epithelia that appeared in the lesion of subpleural fibrosis in order to elucidate the close relationship of lung cancer development with pulmonary interstitial pneumonia. The neogenetic epithelia were histologically subclassified into six types: (i) ciliated bronchial epithelium (CBE); (ii) squamous metaplastic 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, CIE and SIE frequently expressed surfactant apoprotein and SME was characteristic 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 predominant G to A and G to C substitutions without any G to T transversions, results which are somewhat different to previous studies in lung cancers. The present study clearly demonstrated that K-ras mutation appeared in certain histological 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.
Second Department of Pathology, Gunma University School of Medicine, Maebashi, Japan.
A M
AM
Maeshima
A
A
Maeshima
O
O
Kawashima
T
T
Nakajima
D000368:Aged; D000369:Aged, 80 and over; D001059:Apoproteins / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D004252:DNA Mutational Analysis; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics*; D019394:Ki-67 Antigen / Q000378:metabolism; D017563:Lung Diseases, Interstitial / Q000235:genetics / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics*; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011658:Pulmonary Fibrosis / Q000235:genetics* / Q000473:pathology; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism
D001059:Apoproteins; D002272:Carcinoembryonic Antigen; D019394:Ki-67 Antigen; D018396:Mucin-1; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C046616:pulmonary surfactant apoprotein