Her-2/neu overexpression and amplification in uterine papillary serous carcinoma.
OBJECTIVE
Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer characterized by early metastasis, resistance to therapy, and a high mortality rate. Little is known about the biology of these tumors. Smaller studies suggest that Her-2/neu may be involved in the tumorigenesis of this disease. The purpose of this study was to evaluate the protein expression and gene amplification of Her-2/neu in UPSC and to determine its prognostic value.


METHODS
Tumor tissue from 68 patients with UPSC treated at The University of Texas M.D. Anderson Cancer Center from 1989 to 2002 was available. Her-2/neu expression was evaluated by immunohistochemistry (IHC). Overexpression was defined as complete membrane staining in greater than 10% of the cells. In tumors with overexpression of Her-2/neu by IHC, fluorescence in situ hybridization (FISH) was performed to assess gene amplification. Clinical and pathologic information was obtained from medical records.


RESULTS
Twelve (18%) of 68 tumors demonstrated Her-2/neu overexpression. Of these, only two showed gene amplification. When evaluating all 68 patients, Her-2/neu overexpression was associated with a poorer overall survival (OS; P = .008). In our multivariate Cox proportional hazards models, Her-2/neu IHC overexpression, lymph node status, and stage were each associated with OS (P < or = .05).


CONCLUSIONS
Positive IHC overexpression of Her-2/neu was seen in 18% of UPSCs but was rarely correlated with Her-2/neu gene amplification. Overexpression of Her-2/neu was associated with a worse overall prognosis. The use of trastuzumab (Herceptin; Genentech, South San Francisco, CA) in women with UPSC should be further evaluated in a clinical trial setting.
Slomovitz
Brian M
BM
Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 440, Houston, TX 77030-4009, USA.
Broaddus
Russell R
RR
Burke
Thomas W
TW
Sneige
Nour
N
Soliman
Pamela T
PT
Wu
Weiguo
W
Sun
Charlotte C
CC
Munsell
Mark F
MF
Gershenson
David M
DM
Lu
Karen H
KH
D000368:Aged; D000369:Aged, 80 and over; D018283:Cystadenocarcinoma, Papillary / Q000235:genetics* / Q000401:mortality; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate; D014594:Uterine Neoplasms / Q000235:genetics* / Q000401:mortality