Overexpression and activation of EGFR and VEGFR2 in medullary thyroid carcinomas is related to metastasis. Export

@article{citeulike:5839804, abstract = {Therapeutic options for patients with metastatic medullary thyroid carcinoma (MTC) are limited due to lack of effective treatments. Thus, there is a need to thoroughly characterize the pathways of molecular pathogenesis, and to identify potential targets for therapy in MTC. Since EGFR seems to play a crucial role for RET activation, a key feature of MTCs, and several promising EGFR/VEGFR2-targeted drugs have been developed, the present study was designed to investigate whether these proteins are altered in MTCs. We used a well-characterized series of 153 MTCs to evaluate EGFR activation by sequencing and FISH analysis and to perform EGFR and VEGFR2 immunohistochemistry. EGFR tyrosine kinase domain mutations were not a feature of MTCs, however, EGFR polysomy and a strong EGFR expression was detected in 15\% and 13 \% of the tumors, respectively. Interestingly, EGFR was significantly over-expressed in metastases compared to primary tumors (35\% versus 9\%, P=0.002). We also studied whether specific RET mutations had an effect on EGFR, and found a decrease in EGFR polysomies (P=0.006) and a tendency towards lower EGFR expression for the most aggressive RET mutations (918, 883). Concerning VEGFR2, metastasis showed a higher expression than primary tumors (P=2.8x10-8). In this first study investigating the relationship between EGFR, RET, and VEGFR2 in a large MTC series, we found an activation of EGFR and VEGFR2 in metastasis, using both independent and matched primary/metastasis samples. This suggests that some MTC patients may benefit from existing anti-EGFR/VEFGR2 therapies, although additional preclinical and clinical evidence is needed.}, author = {Rodriguez-Antona, Cristina and Pallares, Judith and Montero-Conde, Cristina and Inglada-Perez, Lucia and Castelblanco, Esmeralda and Landa, I\~{n}igo and Leskela, Susanna and Leandro-Garcia, Luis and Lopez-Jimenez, Elena and Let\'{o}n, Rocio and Casc\'{o}n, Alberto and Lerma, Enrique and Martin, M. Carmen and Carralero, M. Carmen and Mauricio, D\'{\i}dac and Cigudosa, Juan and Matias-Guiu, Xavier and Robledo, Mercedes}, citeulike-article-id = {5839804}, citeulike-linkout-0 = {http://dx.doi.org/10.1677/ERC-08-0304}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19776290}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19776290}, day = {23}, doi = {10.1677/ERC-08-0304}, issn = {1479-6821}, journal = {Endocrine-related cancer}, keywords = {cancer, thyroid}, month = {September}, posted-at = {2009-09-25 11:14:54}, priority = {2}, title = {Overexpression and activation of EGFR and VEGFR2 in medullary thyroid carcinomas is related to metastasis.}, url = {http://dx.doi.org/10.1677/ERC-08-0304}, year = {2009} }

TY - JOUR ID - citeulike:5839804 L3 - citeulike-article-id:5839804 N2 - Therapeutic options for patients with metastatic medullary thyroid carcinoma (MTC) are limited due to lack of effective treatments. Thus, there is a need to thoroughly characterize the pathways of molecular pathogenesis, and to identify potential targets for therapy in MTC. Since EGFR seems to play a crucial role for RET activation, a key feature of MTCs, and several promising EGFR/VEGFR2-targeted drugs have been developed, the present study was designed to investigate whether these proteins are altered in MTCs. We used a well-characterized series of 153 MTCs to evaluate EGFR activation by sequencing and FISH analysis and to perform EGFR and VEGFR2 immunohistochemistry. EGFR tyrosine kinase domain mutations were not a feature of MTCs, however, EGFR polysomy and a strong EGFR expression was detected in 15% and 13 % of the tumors, respectively. Interestingly, EGFR was significantly over-expressed in metastases compared to primary tumors (35% versus 9%, P=0.002). We also studied whether specific RET mutations had an effect on EGFR, and found a decrease in EGFR polysomies (P=0.006) and a tendency towards lower EGFR expression for the most aggressive RET mutations (918, 883). Concerning VEGFR2, metastasis showed a higher expression than primary tumors (P=2.8x10-8). In this first study investigating the relationship between EGFR, RET, and VEGFR2 in a large MTC series, we found an activation of EGFR and VEGFR2 in metastasis, using both independent and matched primary/metastasis samples. This suggests that some MTC patients may benefit from existing anti-EGFR/VEFGR2 therapies, although additional preclinical and clinical evidence is needed. JF - Endocrine-related cancer SN - 1479-6821 TI - Overexpression and activation of EGFR and VEGFR2 in medullary thyroid carcinomas is related to metastasis. KW - cancer KW - thyroid AU - Rodriguez-Antona, Cristina AU - Pallares, Judith AU - Montero-Conde, Cristina AU - Inglada-Perez, Lucia AU - Castelblanco, Esmeralda AU - Landa, Iñigo AU - Leskela, Susanna AU - Leandro-Garcia, Luis AU - Lopez-Jimenez, Elena AU - Letón, Rocio AU - Cascón, Alberto AU - Lerma, Enrique AU - Martin, Carmen AU - Carralero, Carmen AU - Mauricio, Dídac AU - Cigudosa, Juan AU - Matias-Guiu, Xavier AU - Robledo, Mercedes PY - 2009/09/23/ UR - http://dx.doi.org/10.1677/ERC-08-0304 ER -