title: Frequent hepatocyte growth factor overexpression and low frequency of c-Met gene amplification in human papillomavirus-negative tonsillar squamous cell carcinoma and their prognostic significances.
abstract: Human papillomavirus (HPV) is an important prognostic factor for tonsillar squamous cell carcinoma (TSCC). HPV-positive and HPV-negative TSCCs are considered distinct in terms of prognosis and sensitivity to chemo/radiotherapy. However, to date, no study has thoroughly evaluated the individual prognostic factors for these 2 disease subgroups. Hepatocyte growth factor (HGF)-Met signaling pathway can be a predictive marker for prognosis or therapy response, especially in HPV-negative TSCC. We therefore investigated the prognostic values of HGF and c-Met expression in TSCC according to HPV status. Immunohistochemical analyses of HGF and c-Met protein expression and silver in situ hybridization of c-Met gene copy number were performed in 79 formalin-fixed, paraffin-embedded specimens. In HPV-negative TSCC, HGF overexpression, regional lymph node category, and ipsilateral cervical nodal metastasis predicted decreased overall survival (OS) (P = .017, P = .024, and P = .003, respectively). The latter 2 were also independent prognostic factors for progression-free survival (P = .023 and P = .002, respectively). In HPV-positive TSCC, heavy alcohol consumption and advanced primary tumor category were predictive of progression-free survival, whereas no independent prognostic factor for OS was identified. HGF overexpression had a significant effect on OS in HPV-negative TSCC but not in HPV-positive TSCC. HPV-negative/HGF-high expression tumors exhibited the worst survival outcomes, whereas HPV-positive/HGF-low expression tumors had the most favorable prognosis. c-Met expression and c-Met gene amplification were not associated with survival outcomes in TSCC patients. In conclusion, HGF may be a potential prognostic marker in HPV-negative TSCC, whereas c-Met exhibited limited clinical significance in TSCC.
authors.affiliation: Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea.
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Kwon
authors.affiliation: Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do 431-070, Republic of Korea.
authors.forename: Hye-Rim
authors.initials: HR
authors.lastname: Park
authors.affiliation: Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 134-701, Republic of Korea.
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Shin
authors.affiliation: Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 134-701, Republic of Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kwon
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Ilsong Memorial Institute Head and Neck Cancer Center, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 134-701, Republic of Korea.
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Lee
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Ilsong Memorial Institute Head and Neck Cancer Center, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 134-701, Republic of Korea.
authors.forename: Jin Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 134-701, Republic of Korea.
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 134-701, Republic of Korea. Electronic address: esnam2003@yahoo.co.kr.
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Nam
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000821:virology; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D014067:Tonsillar Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000821:virology
chemical_list: D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met
keywords: HGF; Human papillomavirus; Squamous cell carcinoma; Tonsil; c-Met