title: Predictive advantage of a cell type classification for pulmonary adenocarcinoma coupled with data for p53, K-ras and EGFR alterations.
abstract: We analyzed relationships between histological subtypes of pulmonary adenocarcinomas and three gene alterations (p53, K-ras, and epidermal growth factor receptor gene), or thyroid transcription factor-1 (TTF-1) expression, and also studied prognoses by the subtypes, with or without combined multiple gene mutation status. Our purpose was to clearly determine pathogenesis, along with the best predictive value for biology and therapy-related traits. A total of 223 consecutively resected pulmonary adenocarcinomas were sub-classified using either the World Health Organization (WHO) or our five-cell type (FCT) classification system (hobnail, columnar/cuboidal, mixed, polygonal/oval, and goblet cell types). DNAs extracted from frozen samples of the adenocarcinomas were examined for gene alterations, and TTF-1 expressions were determined using immunohistochemistry. Next, relationships among the various data and clinicopathological factors were analyzed. The most striking result was: while almost 70% of adenocarcinomas were sub-classified as a mixed subtype by WHO, the FCT classified many of them as other cell subtypes. The FCT closely reflected differences in etiological factors, cellular lineages, and frequencies of gene mutations; and whether the data from combined gene mutations were used or not, differences among the cell types in postoperative survivals appeared. In contrast, subtypes of WHO did not show any association with the gene alteration or prognosis, and the FCT more suitably indicated sensitivity to gefitinib therapy than did WHO. The FCT combined with multiple gene mutation status appears to be useful in indicating pathogenesis and predicting the biological nature of pulmonary adenocarcinomas, and it could facilitate development of new therapies for each subtype.
authors.affiliation: Laboratory of Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Okada
authors.forename: Takuo
authors.initials: T
authors.lastname: Shimmyo
authors.forename: Takehisa
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Ken
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Hayashi
authors.forename: Eiju
authors.initials: E
authors.lastname: Tsuchiya
mesh_terms: D000230:Adenocarcinoma / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D000368:Aged; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014944:World Health Organization
chemical_list: D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors