Expression and amplification of HER-2/neu oncogene in uterine carcinosarcomas: a marker for potential molecularly targeted treatment?
Surgery is the treatment of choice for uterine carcinosarcomas; nevertheless, the poor effect of chemotherapy and radiotherapy represents an insidious problem for patients with metastatic or unresectable disease, and indeed, new therapeutic approaches are clearly required to improve survival of uterine carcinosarcoma patients. The HER-2 oncogene, located on chromosome 17, encodes for a tyrosine kinase growth factor receptor. We analyzed HER-2/neu overexpression by immunohistochemistry in 28 uterine carcinosarcomas. HER-2/neu amplification with fluorescence in situ hybridization (FISH) was tested in positive cases. The expression of HER-2/neu was correlated with disease-free interval and survival (Kaplan-Meier estimates). We observed HER-2/neu overexpression in nine cases (32.1%) and HER-2/neu amplification in all the four HER-2/neu 3+ score positive cases tested by FISH. HER-2/neu expression was not correlated with clinical outcome. Patients with disease limited to the uterus (stages I-II) displayed a significantly better disease-free survival (P= 0.004) and actuarial survival (P= 0.01). Demonstration of HER-2/neu overexpression and amplification in uterine carcinosarcoma may represent the first rationale step for further investigations. Hence, the results of this analysis may support the challenge of a new therapeutic approach, which could test the role of anti-HER-2 (trastuzumab) in patients with advanced or metastatic uterine carcinosarcoma.
Raspollini
M R
MR
Department of Human Pathology and Oncology, University of Florence, School of Medicine, Viale G.B. Morgagni 85, 50134 Florence, Italy. mariarosaria.raspollini@unifi.it
Susini
T
T
Amunni
G
G
Paglierani
M
M
Castiglione
F
F
Garbini
F
F
Carriero
C
C
Scarselli
G
G
Taddei
G L
GL
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002296:Carcinosarcoma / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D016009:Chi-Square Distribution; D015331:Cohort Studies; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D015316:Genetic Therapy; D006801:Humans; D007044:Hysterectomy / Q000379:methods; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D015996:Survival Rate; D046509:Tissue Culture Techniques; D014594:Uterine Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000628:therapy*
D014408:Biomarkers, Tumor