Τομέας Κλινικοεργαστηριακός
Library of the School of Health Sciences

2013-01-08

2012

Παναγιώτου Ιωάννης

Αναπλ. Καθ. Λάζαρης Ανδρέας

Διερεύνηση της απορρύθμισης των γονιδίων HER2/neu και PTEN στο μη μικροκυτταρικό καρκίνο του πνεύμονα

Greek

Introduction. HER2/neu overexpression due to gene amplification is an important
factor in breast cancer modifying the sensitivity to anti-HER-2/neu monoclonal
antibody therapy. The clinical significance of HER2/neu expression in
non-small-cell lung carcinoma (NSCLC) is currently under evaluation. The tumor
suppressor gene PTEN negatively regulates the HER2/PI3K/Akt signalling pathway.
Although the loss of PTEN is not a rare event in NSCLC its prognostic role is
still not well established. Purpose: The purpose of this study was to evaluate
the role of HER2/neu oncogene in both gene and protein level and the role of
PTEN tumor suppressor gene in protein level in NSCLC. Emphasis was given to
investigate the role of simultaneous HER2 and PTEN protein expression
alterations in relation to prognosis of NSCLC patients. Materials and methods:
Surgical specimens were obtained from a total of 61 patients with NSCLC who
underwent a surgical resection. Immunohistochemistry was performed by the use
of anti-HER2/neu monoclonal antibody (TAB 250) and anti-PTEN polyclonal
antibody (PN 37). Chromogenic in situ hybribization was applied based on the
use of HER2/neu gene and chromosome 17 centromeric probes. Protein expression
levels were evaluated using an image analysis system and finally statistical
analysis was performed. Patients followed-up in a period of 3years after the
operation. Results: HER2 overexpression (2+/3+ score) was detected in 17
(27.87%) patients. Additionally, loss of PTEN expression was observed in 24
(39.34%) cases, low expression in 29 (47.54%) and overexpression in 8 (13.12%)
cases. Gene analysis identified 4/61(6.56%) HER2/neu low-level gene amplified
cases. Chromosome 17 analysis detected aneuploidy in 2/61(3.28%) cases.
Simultaneous HER2 overexpression and PTEN low/loss of expression were
correlated to the occurrence of metastases. (71,43% vs 36,17% p=0.03). Strong
relationship between the number of positive regional lymph node stations during
the time of operation and simultaneous deregulation of the two genes was
revealed (p=0.04). Multivariate analysis determined that HER2 overexpression
was associated with an increasing risk of developing metastases (OR: 4.3;
95%CI: 1.2-15.9; p: 0.03) while PTEN overexpression was associated with lower
risk to develop metastases (OR: 0.1; 95%CI: 0.1, 1.0; p: 0.05). Conclusions:
Simultaneous HER2 and PTEN deregulation is a significant genetic event that is
likely to offer in the progression of NSCLC.

Proto-ongogene , Tumor suppressor gene, Non-small cell lung cancer, Immunohistochemistry, Chomogenic in situ hybridization

No

0

Yes

458

X, 203

File access is restricted only to the intranet of UoA.

https://pergamos.lib.uoa.gr/uoa/dl/object/1306020