Amplification of c-erbB2 oncogene: a major prognostic indicator in uterine serous papillary carcinoma.
BACKGROUND
Overexpression of the epidermal growth factor type II receptor HER-2/neu has been associated with resistance to chemotherapy and poor survival in several human tumors. In the current study, the authors have determined the frequency and clinical significance of HER-2/neu gene amplification in uterine serous papillary endometrial carcinoma (USPC), a highly aggressive variant of endometrial carcinoma.


METHODS
Fluorescence in situ hybridization (FISH) assay was used to analyze gene amplification in paraffin blocks from 30 women harboring Stage IA-IV USPC treated at the University of Arkansas for Medical Sciences (Little Rock, AR) from 1997 to 2004. Chromosome 17 polysomy status by FISH was also assessed in all specimens. USPC patient survival in relation to HER-2/neu gene amplification was analyzed using Kaplan-Meier curves in conjunction with the log-rank test.


RESULTS
Amplification of the HER-2/neu gene by FISH was observed in 14 of the 30 (47%) cases. Heterogeneity was noted in 4 of 14 cases in the amplification of the HER-2/neu gene within the same tumor samples with pockets of amplified tumor cells amidst nonamplified tumor cells. Patients with USPC harboring tumors with HER-2/neu gene amplification had a significantly shorter survival time from diagnosis to disease-related death when compared with FISH-negative patients (P = 0.0008). African-American (AA) patients were found to have a poorer prognosis compared with Caucasian (C) women (P = 0.01) and to harbor USPC with significantly higher levels of HER-2/neu gene amplification (P = 0.02).


CONCLUSIONS
HER-2/neu gene amplification in USPC was found to be an important prognostic indicator for poor outcome that occurs more frequently in AA when compared with C patients. Determination of HER-2/neu gene amplification may guide clinical management of patients with USPC and may have important implications for the implementation of novel treatment strategies.
Santin
Alessandro D
AD
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205-7199, USA. santinalessandrod@uams.edu
Bellone
Stefania
S
Van Stedum
Sue
S
Bushen
Wendy
W
Palmieri
Michela
M
Siegel
Eric R
ER
De Las Casas
Luis E
LE
Roman
Juan J
JJ
Burnett
Alexander
A
Pecorelli
Sergio
S
D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D018283:Cystadenocarcinoma, Papillary / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D014594:Uterine Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases