Correlation Of Immunohistochemistry And Silver In Situ Hybridization For The Assessment Of C-Met In Uterine Cervical Cancer Patients Treated With Radical Hysterectomy

Objectives: The aim of this study was to compare c-MET protein overexpression and gene copy number (GCN) in uterine cervical cancer and to assess their prognostic significance. Methods: c-MET protein expression and GCN status were determined using immunohistochemistry (IHC) and silver in situ hybridization (SISH), respectively, in 117 cervical cancers comprising 83 squamous cell carcinomas (SCCs), 23 adenocarcinomas (ACs), 7 adenosquamous cell carcinomas (ASCCs), and 4 other types. Results: Forty-five of 117 (38.5%) cervical cancer patients had c-MET protein overexpression (IHC 2+ in 40 cases and IHC 3+ in 5 cases). The frequency of overexpression was 31.3% in SCCs, 73.9% in ACs, 14.3% in ASCCs and 25.0% in other types. IHC 3+ c-MET protein overexpression was observed only in ACs and correlated with worse overall survival (OS) (p = 0.001) and progression-free survival (PFS) (p < 0.001). High polysomy (HP) of chromosome 7 and gene amplification (GA) were found in 6 (5.1%) and 0 of the 117 cervical cancers, respectively. Of the 6 HP cases, 3 were SCCs and 3 were ACs. GCN could not be determined in 16 (13.7%) of the 117 cases. HP cases showed a trend for worse prognosis than cases with negative c-MET SISH, but this did not reach statistical significance (OS, p = 0.307; PFS,p = 0.184). Nonetheless, c-MET protein overexpression and increased GCN were significantly correlated (r = 0.228,p = 0.022). Conclusions: c-MET, evaluated using IHC and GCN, may be a prognostic biomarker of poor prognosis in patients with cervical AC.