HER-2/neu amplification and overexpression in endometrial carcinoma

HER-2/neu is a proto-oncogene associated with poor prognosis in women with breast and ovarian carcinoma. The significance of HER-2/neu in endometrial carcinoma is less clearly established. The authors compared HER-2/neu gene amplification using fluorescence in situ hybridization and protein overexpr ession using immunohistochemistry with survival in patients with endometria l carcinoma. Fluorescence in situ hybridization and immunohistochemical sta ining were performed on 72 formalin-fixed, paraffin-embedded endometrial ca rcinoma specimens. Vysis combination HER-2/neu and centromere 17 probe mixt ure was applied to isolated tumor cell nuclei. A minimum of 200 nuclei were scored for each specimen using standard signal enumeration criteria. A spe cimen was considered amplified with 5% or greater amplified nuclei. Tissue sections were immunostained with polyclonal antibody against p185erb-2 tran smembrane glycoprotein. Immunohistochemical reactivity was scored on a thre e-tiered scale. HER-2/neu gene amplification and protein overexpression wer e detected in 15 of 72 (21%) and 12 of 72 (17%) of the specimens, respectiv ely, with 2 casts of normal copy overexpression and 5 cases of amplificatio n without overexpression. Both amplification and overexpression were associ ated with higher grade tumors. Amplification was associated with clear cell and serous subtypes (p = 0.002) and overexpression with only clear cell ty pe (p = 0.006). Using the proportional hazards model of survival, amplifica tion was found to have significant negative predictive value beyond stage, grade, and cell type (p = 0.002). HER-2/neu gene amplification as detected by fluorescence in situ hybridization in archival material has significant prognostic value.