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

• Published in: Anticancer research Vol. 25; no. 4; pp. 2921 - 2927
• Main Authors: MARIANI, Andrea, SEBO, Thomas J, KATZMANN, Jerry A, RIEHLE, Darren L, DOWDY, Sean C, KEENEY, Gary L, LESNICK, Timothy G, PODRATZ, Karl C
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01-07-2005
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Cohort Studies; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - pathology; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Middle Aged; Neoplasms, Hormone-Dependent - metabolism; Neoplasms, Hormone-Dependent - pathology; Receptor, ErbB-2 - biosynthesis; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Tumors; Hormone; Estrogen receptor; Endometrium cancer; Endometrial cancer; progesterone receptors; erbB2 Gene; Gene overexpression; Malignant tumor; Progesterone receptor; estrogen receptors; Female genital diseases; Cancerology; Cohort study; C-Onc gene; Uterine diseases; HER-2/neu; hormone dependency; Protooncogene; Bibliographic review; Hormonal receptor
• ISSN: 0250-7005; 1791-7530

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.