HER-2/neu oncogene amplification and chromosome 17 aneusomy in endometrial carcinoma: correlation with oncoprotein expression and conventional pathological parameters.
The objective of the present study was to evaluate the correlation between HER-2 gene amplification and HER-2 protein overexpression in endometrial carcinoma using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We also analyzed chromosome 17 aneusomy and the association between these biological parameters and conventional clinicopathological variables. FISH analysis was performed on 73 selected paraffin-embedded sections from endometrial carcinomas which previously had HER-2 status determined immunohistochemically using monoclonal antibodies (MoAb) 300G9 and CB11. Using a ratio of more than two oncogene signals/centromere to indicate amplification, a total of 42 out of the 73 endometrial tumors included in this study resulted positive by FISH where as protein overexpression was identified in 29 out of 73 with a concordance rate of 74.3%. However, when the mean signals/centromere per nucleus increased (ratio > 4 < or = 5) a higher concordance between the two assays was seen (p = 0.007). In addition, HER-2 amplification was significantly correlated with tumor stage (p = 0.021) and myometrial invasion (p = 0.010), whereas chromosome 17 polisomy showed a positive correlation only with myometrial invasion (p = 0.004) No significant correlation was found between HER-2 gene amplification, chromosome 17 aneusomy and patient outcome. Nevertheless, the probability of a 5 year overall survival decreased from 70% to 43%, respectively, for ratio > 2 < or = 4 and ratio > 4 < or = 5 when we grouped the amplified cases on the basis of HER-2:CEP17 ratio. In conclusion, molecular characteristics provide objective data that may be useful in predicting prognosis in patients with endometrial cancer.
Cianciulli
A M
AM
Dept. of Clinical Pathology, Regina Elena Cancer Institute, Rome, Italy. cianciulli@ifo.it
Guadagni
F
F
Marzano
R
R
Benevolo
M
M
Merola
R
R
Giannarelli
D
D
Marandino
F
F
Vocaturo
G
G
Mariani
L
L
Mottolese
M
M
D000911:Antibodies, Monoclonal / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009215:Myometrium / Q000473:pathology; D009361:Neoplasm Invasiveness; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D013997:Time Factors
D000911:Antibodies, Monoclonal; D018719:Erb-b2 Receptor Tyrosine Kinases