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Conference Paper: An Interim Report Of CALGB 150607: Expression And Mutational Status Of c-MET, HGF, EGFR, KRAS, p53, c-CBL, And E-cadherin In Resected Lung Adenocarcinoma Specimens
Title | An Interim Report Of CALGB 150607: Expression And Mutational Status Of c-MET, HGF, EGFR, KRAS, p53, c-CBL, And E-cadherin In Resected Lung Adenocarcinoma Specimens |
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Authors | |
Issue Date | 2012 |
Publisher | Lippincott Williams & Wilkins. |
Citation | The 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL., 6-8 September 2012. In Journal of Thoracic Oncology, 2012, v. 7 n. 9 suppl., p. S245-S246, abstract no. 190 How to Cite? |
Abstract | PURPOSE/OBJECTIVE(S): c-Met is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor plays a critical role in cancer growth, invasion, and metastasis. The main objective of this study is to evaluate the correla¬tion between c-MET mutation and expression with stage and overall survival in a large group of adenocarcinoma (AC) patients. The secondary aims are to determine the correlation between overall survival and the analysis of: 1) EGFR mutation & expression, 2) TP53 mutation & expression, 3)epithelial-to-mesenchymal transition, 4) KRAS mutation, and 5) CBL mutation, and to evaluate gene amplification of c-MET in AC patients and the sera levels of circulating c-Met and HGF. MATERIALS/METHODS: We evaluated 80 adenocarcinoma patients. Standard PCR and sequencing techniques for mutational analysis of MET, EGFR exons 18-21, TP53 exons 4-10, KRAS exon 2, and CBL exons 2-16. ELISA was used to quantify soluble c-Met and HGF in pre- and post-operative sera. c-MET, phosphorylated (pMET Y1003 and Y1230/34/35), p53, HGF, EGFR, and E-cadherin expression were evaluated by IHC. Staining inten¬sity was scored on four-point scale: 0, negative; 1+, weak; 2+, moderate; 3+, strong. The extent of staining was scored similarly: 0, negative; 1+, 1-10%; 2+, 11-50%; 3+, > 50%. The product of the intensity and extent of staining yielded final scores between 0 and 9. RESULTS: In 9 patients, six non-synonymous (NS) mutations were detected in MET (SEMA domain: E168D, M362T, N375S, and Q318K; JM domain: T992I and R970C). In EGFR, the NS mutation L858R was detected in two patients. We detected 11 NS mutations in TP53 (exon 4: E68*; exon 5: V157F, R175H, I162F, H193Y, Y163D; exon 8: R273L, R273C, V274L, A276F, and G266*). Five NS mutations were detected in exon 2 of KRAS (G12C, G12V, G12D, G12S and G13V). For both c-MET and HGF, there are 65 pairs pre- and post-operative sera with no missing values. There was a significant (p=0.008) increase of soluble c-MET in post- (1750 ng/ml ± 60.2) compared to pre-operative (1584 ng/ml ± 59.2) serum samples. HGF levels were significantly increased (p=0.028) in post- (1006 pg/ml ± 70.6) com¬pared to pre-operative samples (847 pg/ml ± 56.0). The mean expressions as determined by IHC: c-MET 3.9 (±0.3); pY1230/34/35 MET 2.3 (±0.3); pY1003MET 4.8 (±0.3); HGF 4.4 (±0.3); EGFR 4.3 (±0.4); TP53 3.8 (±0.3); and E-cadherin 5.4 (±0.4) CONCLUSION: Unique MET mutations were detected in key functional domains; the SEMA domain and the JM domain. Post-operative patient sera levels were increased dramatically both in HGF and soluble MET. MET, pMET (Y1003), EGFR, E-Cadherin, HGF and P53 were highly expressed. The expression and mutation data will be correlated with clinical outcomes to identify the prognostic role of c-Met. |
Description | Plenary Session: no. 190 |
Persistent Identifier | http://hdl.handle.net/10722/195789 |
ISSN | 2023 Impact Factor: 21.0 2023 SCImago Journal Rankings: 7.879 |
DC Field | Value | Language |
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dc.contributor.author | Salgia, R | en_US |
dc.contributor.author | Nallasura, V | en_US |
dc.contributor.author | Pang, HMH | en_US |
dc.contributor.author | Rolle, CE | en_US |
dc.contributor.author | Richards, W | en_US |
dc.contributor.author | Hodgson, L | en_US |
dc.contributor.author | Arif, Q | en_US |
dc.contributor.author | Husain, A | en_US |
dc.contributor.author | Kratzke, R | en_US |
dc.contributor.author | Vokes, EE | en_US |
dc.date.accessioned | 2014-03-10T04:53:30Z | - |
dc.date.available | 2014-03-10T04:53:30Z | - |
dc.date.issued | 2012 | en_US |
dc.identifier.citation | The 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL., 6-8 September 2012. In Journal of Thoracic Oncology, 2012, v. 7 n. 9 suppl., p. S245-S246, abstract no. 190 | en_US |
dc.identifier.issn | 1556-0864 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/195789 | - |
dc.description | Plenary Session: no. 190 | - |
dc.description.abstract | PURPOSE/OBJECTIVE(S): c-Met is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor plays a critical role in cancer growth, invasion, and metastasis. The main objective of this study is to evaluate the correla¬tion between c-MET mutation and expression with stage and overall survival in a large group of adenocarcinoma (AC) patients. The secondary aims are to determine the correlation between overall survival and the analysis of: 1) EGFR mutation & expression, 2) TP53 mutation & expression, 3)epithelial-to-mesenchymal transition, 4) KRAS mutation, and 5) CBL mutation, and to evaluate gene amplification of c-MET in AC patients and the sera levels of circulating c-Met and HGF. MATERIALS/METHODS: We evaluated 80 adenocarcinoma patients. Standard PCR and sequencing techniques for mutational analysis of MET, EGFR exons 18-21, TP53 exons 4-10, KRAS exon 2, and CBL exons 2-16. ELISA was used to quantify soluble c-Met and HGF in pre- and post-operative sera. c-MET, phosphorylated (pMET Y1003 and Y1230/34/35), p53, HGF, EGFR, and E-cadherin expression were evaluated by IHC. Staining inten¬sity was scored on four-point scale: 0, negative; 1+, weak; 2+, moderate; 3+, strong. The extent of staining was scored similarly: 0, negative; 1+, 1-10%; 2+, 11-50%; 3+, > 50%. The product of the intensity and extent of staining yielded final scores between 0 and 9. RESULTS: In 9 patients, six non-synonymous (NS) mutations were detected in MET (SEMA domain: E168D, M362T, N375S, and Q318K; JM domain: T992I and R970C). In EGFR, the NS mutation L858R was detected in two patients. We detected 11 NS mutations in TP53 (exon 4: E68*; exon 5: V157F, R175H, I162F, H193Y, Y163D; exon 8: R273L, R273C, V274L, A276F, and G266*). Five NS mutations were detected in exon 2 of KRAS (G12C, G12V, G12D, G12S and G13V). For both c-MET and HGF, there are 65 pairs pre- and post-operative sera with no missing values. There was a significant (p=0.008) increase of soluble c-MET in post- (1750 ng/ml ± 60.2) compared to pre-operative (1584 ng/ml ± 59.2) serum samples. HGF levels were significantly increased (p=0.028) in post- (1006 pg/ml ± 70.6) com¬pared to pre-operative samples (847 pg/ml ± 56.0). The mean expressions as determined by IHC: c-MET 3.9 (±0.3); pY1230/34/35 MET 2.3 (±0.3); pY1003MET 4.8 (±0.3); HGF 4.4 (±0.3); EGFR 4.3 (±0.4); TP53 3.8 (±0.3); and E-cadherin 5.4 (±0.4) CONCLUSION: Unique MET mutations were detected in key functional domains; the SEMA domain and the JM domain. Post-operative patient sera levels were increased dramatically both in HGF and soluble MET. MET, pMET (Y1003), EGFR, E-Cadherin, HGF and P53 were highly expressed. The expression and mutation data will be correlated with clinical outcomes to identify the prognostic role of c-Met. | - |
dc.language | eng | en_US |
dc.publisher | Lippincott Williams & Wilkins. | en_US |
dc.relation.ispartof | Journal of Thoracic Oncology | en_US |
dc.title | An Interim Report Of CALGB 150607: Expression And Mutational Status Of c-MET, HGF, EGFR, KRAS, p53, c-CBL, And E-cadherin In Resected Lung Adenocarcinoma Specimens | en_US |
dc.type | Conference_Paper | en_US |
dc.identifier.email | Pang, HMH: herbpang@hku.hk | en_US |
dc.identifier.authority | Pang, HMH=rp01857 | en_US |
dc.identifier.doi | 10.1097/JTO.0b013e318269fc07 | - |
dc.identifier.volume | 7 | en_US |
dc.identifier.issue | 9 suppl. | - |
dc.identifier.spage | S245, abstract no. 190 | en_US |
dc.identifier.epage | S246 | en_US |
dc.publisher.place | United States | en_US |
dc.identifier.issnl | 1556-0864 | - |