HER-2/neu overexpression and amplification in uterine serous papillary carcinoma: comparative analysis of immunohistochemistry, real-time reverse transcription-polymerase chain reaction, and fluorescence in situ hybridization.
Uterine serous papillary carcinoma (USPC) is a rare and highly malignant form of endometrial cancer (EC) characterized by early metastasis, chemoresistance, and high mortality rate. Little is known about USPC tumorigenesis even if recently a HER-2/neu role has been suggested in its development and progression. The aim of the present study was to evaluate HER-2 expression by immunohistochemistry (IHC) in 12 USPC formalin-fixed, paraffin-embedded (FFPE) samples. Moreover, we looked at the correlation between HER-2 protein expression and HER-2/neu gene amplification by fluorescence in situ hybridization (FISH), other than HER-2/neu messenger RNA expression by quantitative real-time reverse transcription (RT)-polymerase chain reaction (PCR). Finally, these results have been compared with commonly evaluated clinical features in EC patients, in order to define the potential prognostic value of HER-2/neu overexpression in USPCs. A high expression of HER-2 protein by IHC was noted in 2 of 12 patients (16.6%), and the same cases showed specific HER-2/neu gene amplification by FISH. All the samples investigated displayed a perfect concordance between IHC and FISH data. Five (41.6%) of 12 tumors demonstrated polysomy of chromosome 17 and, focusing on the 2 USPCs that showed HER-2/neu overexpression, one of them (50%) was polysomic for chromosome 17. All the other USPC cases (58.4%) showed to be disomic for chromosome 17. Quantitative RT real-time PCR performed on complementary DNA obtained from all FFPE USPC samples showed a complete correlation with FISH and IHC data. Moreover, HER-2/neu overexpression was associated with a poorer overall survival and a very low relapse-free survival time, thus being considered a candidate marker of worse overall prognosis in USPC. The use of trastuzumab (Herceptin), a monoclonal antibody directed against HER-2/neu, for the therapy of patients with HER-2/neu-positive USPCs should be further investigated in clinical trials.
Odicino
F E
FE
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Brescia, Brescia, Italy. fodicino@tiscali.it
Bignotti
E
E
Rossi
E
E
Pasinetti
B
B
Tassi
R A
RA
Donzelli
C
C
Falchetti
M
M
Fontana
P
P
Grigolato
P G
PG
Pecorelli
S
S
D000368:Aged; D000369:Aged, 80 and over; D018283:Cystadenocarcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D016612:Paraffin Embedding; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
D018719:Erb-b2 Receptor Tyrosine Kinases