title: Prognostic value of KRAS mutations and Ki-67 expression in stage I lung adenocarcinomas.
abstract: The purpose of the present study was to establish accurate prognostic markers to predict the post-operative recurrence of stage I lung adenocarcinomas (ADC). One-hundred and ninety cases of stage I ADC were examined for KRAS mutations and Ki-67 expression, and their associations with disease recurrence were analyzed. KRAS-mutated cases showed a significantly higher risk of recurrence than cases without mutations (5-year disease-free survival (DFS) 61.0% vs. 85.8%, P=0.017: adjusted Hazard ratio (HR) 4.55, 95% Confidence Interval (CI) 1.61-12.82, P=0.004). Ki-67 high-expressers (labeling index >10%) also showed a higher risk of recurrence than low-expressers (5-year DFS 68.7% vs. 93.2%, P<0.001: adjusted HR 3.84, 95% CI 1.18-12.45, P=0.025). Ki-67 high-expressers with KRAS mutations showed an additional higher risk of recurrence compared to low-expressers without mutations (5-year DFS 37.5% vs. 93.3%, P<0.001: adjusted HR 16.82, 95% CI 3.77-74.98, P<0.001) and their 5-year DFS was nearly equivalent to that of stage II non-small cell lung cancer (NSCLC) in our facility (37.5% vs. 37.2% for stage II NSCLC, p=0.577). The combined use of KRAS status and Ki-67 expression level could be an excellent prognostic marker to predict the post-operative recurrence of stage I ADC.
authors.affiliation: Division of Thoracic Surgery, Kanagawa Prefectural Cardiovascular and Respiratory Center Hospital, Yokohama, Japan. tetsu.n.u@cotton.ocn.ne.jp
authors.forename: Tetsukan
authors.initials: T
authors.lastname: Woo
authors.forename: Koji
authors.initials: K
authors.lastname: Okudela
authors.forename: Takuya
authors.initials: T
authors.lastname: Yazawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Wada
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ogawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiwa
authors.forename: Michihiko
authors.initials: M
authors.lastname: Tajiri
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Rino
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kitamura
authors.forename: Munetaka
authors.initials: M
authors.lastname: Masuda
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D012008:Recurrence; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins