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 im-munohistochemistry (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 overexpres-sion 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.

Cervical cancer; C-MET; Immunohistochemistry; Silver in situ hybridization; Prognosis.

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