HER-2/neu Overexpression and Hormone Dependency in Endometrial Cancer: Analysis of Cohort and Review of Literature

Abstract

Background: Overexpression of HER-2/neu (HER) is associated with unfavorable prognoses in both endometrial and breast cancer. Materials and Methods: To determine whether an association exists between HER expression and markers of hormone dependency in endometrial cancers, we subjected hysterectomy specimens from 125 patients to immuno-histochemical staining for HER. HER was visually interpreted as negative/weakly positive (HER-) versus strongly positive (HER+). Estrogen receptor (ER) and progesterone receptor (PR) levels were quantitated on fresh tissue using a dextran-coated charcoal assay. Results: HER+ was observed in 12% of endometrioid tumors and 22% of nonendometrioid tumors (p=0.07). Mean ER and PR levels were 255 fmol/mg and 457 fmol/mg in endometrioid tumors, compared with 74 and 104 in nonendometrioid tumors (p<0.01). Hyperplasia associated with the tumor was related to high levels of both ER and PR (p<0.05), but not with HER expression. Age was significantly related to high levels of ER (p=0.007). Both recurrence and death rates were significantly associated with low levels of ER and PR (p<0.01). Mean ER and PR levels were 270 and 466 fmol/mg, respectively, in HER-tumors, compared with 95 (p=0.14) and 138 fmol/mg (p=0.02) in HER+ tumors. Conclusion: HER overexpression may be an important step in hormone-independent growth and proliferation in a subgroup of endometrial cancers.