title: Detection and discrimination of preneoplastic and early stages of lung adenocarcinoma using hnRNP B1 combined with the cell cycle-related markers p16, cyclin D1, and Ki-67.
abstract: Heterogeneous nuclear ribonucleoprotein B1 (hnRNP B1), an RNA binding protein, is a useful marker for early detection of lung squamous cell carcinoma because it is overexpressed in the early stages of lung cancer, including bronchial dysplasia, a premalignant lesion of lung squamous cell carcinoma. In the case of adenocarcinoma, we investigated the utility of hnRNP B1 for both detection of early adenocarcinoma and discrimination of non-invasive lesion, atypical adenomatous hyperplasia (AAH) from adenocarcinoma. hnRNP B1, cyclin D1, p16, and Ki-67 were analyzed in lung adenocarcinoma tissues and divided into early and overt adenocarcinoma and AAH, using immunohistochemistry. The intensity of these molecular markers was compared among three groups and also analyzed for 4 patients who showed both adenocarcinoma and AAH. Thirty-six of 54 (67%) adenocarcinoma patients showed positive staining of hnRNP B1: 14/20 (70%) early adenocarcinoma and 22/34 (65%) overt adenocarcinoma. In contrast, overexpression of hnRNP B1 in non-invasive lesion, AAH was observed in only 9% (1/11). Overexpression of cyclin D1 and decrease of p16 were frequently observed in both adenocarcinoma and AAH. These results suggest that hnRNP B1 would be a candidate of molecular marker for detection of early lung adenocarcinoma. In addition, combined analysis of hnRNP B1 and cell cycle-related genes, such as cyclin D1 and p16, might aid in discrimination of AAH from early adenocarcinoma.
authors.affiliation: Department of Pathology, Saga Medical School, Saga 849-8501, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Tominaga
authors.forename: Naoko
authors.initials: N
authors.lastname: Sueoka
authors.forename: Koji
authors.initials: K
authors.lastname: Irie
authors.forename: Kentaro
authors.initials: K
authors.lastname: Iwanaga
authors.forename: Osamu
authors.initials: O
authors.lastname: Tokunaga
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Hayashi
authors.forename: Kei
authors.initials: K
authors.lastname: Nakachi
authors.forename: Eisaburo
authors.initials: E
authors.lastname: Sueoka
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor; D019938:Cyclin D1; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018450:Disease Progression; D005260:Female; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D006801:Humans; D006965:Hyperplasia / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; C439768:hnRNP A2; D019938:Cyclin D1