title: Clinical and prognostic value of MET gene copy number gain and chromosome 7 polysomy in primary colorectal cancer patients.
abstract: We aimed to explore the clinical and prognostic influence of numeric alterations of MET gene copy number (GCN) and chromosome 7 (CEP7) CN in colorectal cancer (CRC) patients. MET GCN and CEP7 CN were investigated in tissue arrayed tumors from 170 CRC patients using silver in situ hybridization (SISH). MET GCN gain was defined as ≥4 copies of MET, and CEP7 polysomy was prespecified as ≥3 copies of CEP7. Additionally, MET messenger RNA (mRNA) transcription was evaluated using mRNA ISH and compared with MET GCN. MET GCN gain was observed in 14.7 % (25/170), which correlated with advanced stage (P = 0.037), presence of distant metastasis (P = 0.006), and short overall survival (OS) (P = 0.009). In contrast, CEP7 polysomy was found in 6.5 % (11/170), which was related to tumor location in the left colon (P = 0.027) and poor OS (P = 0.029). MET GCN positively correlated with CEP7 CN (R = 0.659, P < 0.001) and mRNA transcription (R = 0.239, P = 0.002). Of note, MET GCN gain and CEP7 polysomy were also associated with poor OS (P = 0.016 and P < 0.001, respectively) in stage II/III CRC patients (n = 123). In multivariate analysis, CEP7 polysomy was an independent prognostic factor for poor OS in all patients (P = 0.009; hazard ratio [HR], 2.220; 95 % confidence interval [CI], 1.233-3.997) and in stage II/III CRC patients (P < 0.001; HR, 20.781; 95 % CI, 4.600-93.882). MET GCN gain and CEP7 polysomy could predict a poor outcome in CRC patients, especially CEP7 polysomy has the most powerful prognostic impact in stage II/III CRC patients.
authors.affiliation: Department of Pathology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: An Na
authors.initials: AN
authors.lastname: Seo
authors.affiliation: Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
authors.forename: Kyoung Un
authors.initials: KU
authors.lastname: Park
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea.|Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Gheeyoung
authors.initials: G
authors.lastname: Choe
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
authors.forename: Duck-Woo
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
authors.forename: Sung-Bum
authors.initials: SB
authors.lastname: Kang
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea. hye2@snu.ac.kr.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*
chemical_list: C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: Chromosome 7; Colorectal cancer; Copy number gain; MET; Silver in situ hybridization