Biomarcador Estômago

Analysis of EGFR, HER2, and TOP2A gene status and chromosomal polysomy in gastric adenocarcinoma from Chinese patients

Escrito por Carla Brito Lopes

Background
The EGFR and HER2 genes are located on chromosomes 7 and 17, respectively. They are therapeutic targets in some tumors. The TOP2A gene, which is located near HER2 on chromosome 17, is the target of many chemotherapeutic agents, and co-amplification of HER2 and TOP2A has been described in several tumor types. Herein, we investigated the gene status of EGFR, HER2, and TOP2A in Chinese gastric carcinoma patients. We determined the rate of polysomy for chromosomes 7 and 17, and we attempted to clarify the relationship between EGFR, HER2, and TOP2A gene copy number and increased expression of their encoded proteins. Furthermore, we tried to address the relationship between alterations in EGFR, HER2, and TOP2A and chromosome polysomy.

Methods
One hundred cases of formalin fixed and paraffin embedded tumor tissues from Chinese gastric carcinoma patients were investigated by immunohistochemistry and fluorescence in situ hybridization (FISH) methods.

Results
Forty-two percent of the cases showed EGFR overexpression; 16% showed EGFR FISH positive; 6% showed HER2 overexpression; and 11% showed HER2 gene amplification, including all six HER2 overexpression cases. TOP2A nuclear staining (nuclear index, NI) was determined in all 100 tumors: NI values ranged from 0.5 – 90%. Three percent of the tumors showed TOP2A gene amplification, which were all accompanied by HER2 gene amplification. Nineteen percent of the tumors showed chromosome 7 polysomy, and 16% showed chromosome 17 polysomy. Chromosome 7 polysomy correlated significantly with EGFR FISH-positivity, but was not associated with EGFR overexpression. HER2 overexpression associated significantly with HER2 gene amplification. TOP2A gene amplification was significantly associated with HER2 gene amplification. No relationship was found between alterations in the EGFR, HER2, and TOP2A genes and clinicopathologic variables of gastric carcinoma.

Conclusion
The data from our study suggest that chromosome 7 polysomy may be responsible for increased EGFR gene copy number in gastric carcinomas, and that HER2 gene amplification may be the major reason for HER2 protein overexpression. A combined investigation of the gene status of EGFR, HER2, and TOP2A should facilitate the identification of a target therapeutic regimen for gastric carcinoma patients.

Pode descarregar o artigo completo aqui:http://www.biomedcentral.com/1471-2407/8/363


Liang, Zhiyong;  Zeng, Xuan;  Gao, Jie;  Wu, Shafei;  Wang, Peng et al. (2008)
BMC Cancer vol. 8 (1) p. 363]. Reprinted with permission under the terms of the Creative Commons Attribution License.

Sobre o autor

Carla Brito Lopes

Carla nasceu a 14 de Fevereiro de 1977 em Viana do Castelo. Completou o bacharelato em Anatomia Patológica, Citológica e Tanatológica na ESTES-Porto em 1998 e licenciou-se em 2001 pela Escola Superior de Tecnologia da Saúde em Lisboa. Concluiu a certificação em Laboratory Management pela ASCP (American Association of Clinical Pathology) em Setembro de 2016.
Actualmente encontra-se a frequentar mestrado em Genética Molecular e Biomedicina na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa.