Thang N Tran1, Christina I Selinger1, Maija R J Kohonen-Corish2, Brian McCaughan3, Catherine Kennedy3, Sandra A O'Toole4, Wendy A Cooper5. 1. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. 2. Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; School of Medicine, University of Western Sydney, New South Wales, Australia; St Vincent's Clinical School, University of New South Wales, New South Wales, Australia. 3. Sydney Cardiothoracic Surgeons, Royal Prince Alfred Medical Centre, New South Wales, Australia. 4. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Sydney Medical School, University of Sydney, New South Wales, Australia. 5. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; School of Medicine, University of Western Sydney, New South Wales, Australia; Sydney Medical School, University of Sydney, New South Wales, Australia. Electronic address: Wendy.Cooper@sswahs.nsw.gov.au.
Abstract
INTRODUCTION: Mesenchymal epithelial transition factor (MET) is a promising therapeutic target in non-small-cell lung cancer (NSCLC) but there are limited data about MET alterations in treatment-naive NSCLC and whether or not these changes are consistent between primary tumors and metastases. We aimed to investigate concordance, clinicopathological correlations, and prognostic value of MET alterations in primary NSCLC and corresponding nodal metastases. MATERIALS AND METHODS: MET gene copy number (GCN) status was evaluated using fluorescent in situ hybridization (FISH) and MET protein expression using immunohistochemistry (IHC) in tissue microarray sections from a retrospective cohort of 300 surgically resected NSCLCs including 93 cases with nodal metastases. RESULTS: Primary NSCLCs were MET IHC positive in 28 (10.3%) of cases and MET FISH positive (high polysomy or amplification) in 22 (8.1%) but only 1 (0.4%) showed amplification. In metastases, high MET GCN (18.3%) and protein expression (21.3%) was more frequent compared with primary tumors. The status of MET in lymph nodes significantly correlated with MET status in the corresponding primary tumors. Squamous cell carcinomas showed lower MET overexpression compared with nonsquamous tumors but there were no other associations with clinicopathological characteristics. Patients with tumors that were either MET FISH positive or IHC positive had a significantly better overall survival in univariate and multivariate analyses. CONCLUSION: Alterations of MET are more commonly seen in nodal metastases than primary tumors and this might have implications for their utility as predictive biomarkers to select patients for MET inhibition. MET overexpression and MET high polysomy occur in a low proportion of primary NSCLCs and is associated with a good prognosis.
INTRODUCTION: Mesenchymal epithelial transition factor (MET) is a promising therapeutic target in non-small-cell lung cancer (NSCLC) but there are limited data about MET alterations in treatment-naive NSCLC and whether or not these changes are consistent between primary tumors and metastases. We aimed to investigate concordance, clinicopathological correlations, and prognostic value of MET alterations in primary NSCLC and corresponding nodal metastases. MATERIALS AND METHODS: MET gene copy number (GCN) status was evaluated using fluorescent in situ hybridization (FISH) and MET protein expression using immunohistochemistry (IHC) in tissue microarray sections from a retrospective cohort of 300 surgically resected NSCLCs including 93 cases with nodal metastases. RESULTS: Primary NSCLCs were MET IHC positive in 28 (10.3%) of cases and MET FISH positive (high polysomy or amplification) in 22 (8.1%) but only 1 (0.4%) showed amplification. In metastases, high MET GCN (18.3%) and protein expression (21.3%) was more frequent compared with primary tumors. The status of MET in lymph nodes significantly correlated with MET status in the corresponding primary tumors. Squamous cell carcinomas showed lower MET overexpression compared with nonsquamous tumors but there were no other associations with clinicopathological characteristics. Patients with tumors that were either MET FISH positive or IHC positive had a significantly better overall survival in univariate and multivariate analyses. CONCLUSION: Alterations of MET are more commonly seen in nodal metastases than primary tumors and this might have implications for their utility as predictive biomarkers to select patients for MET inhibition. MET overexpression and MET high polysomy occur in a low proportion of primary NSCLCs and is associated with a good prognosis.
Authors: Christina I Selinger; Bob T Li; Nick Pavlakis; Matthew Links; Anthony J Gill; Adrian Lee; Stephen Clarke; Thang N Tran; Trina Lum; Po Y Yip; Lisa Horvath; Bing Yu; Maija R J Kohonen-Corish; Sandra A O'Toole; Wendy A Cooper Journal: Histopathology Date: 2016-11-15 Impact factor: 5.087
Authors: Gareth Rivalland; Paul Mitchell; Carmel Murone; Khashayer Asadi; Adrienne L Morey; Maud Starmans; Paul C Boutros; Marzena Walkiewicz; Benjamin Solomon; Gavin Wright; Simon Knight; Thomas John Journal: Transl Lung Cancer Res Date: 2019-04
Authors: Samer Al-Saad; Elin Richardsen; Thomas K Kilvaer; Tom Donnem; Sigve Andersen; Mehrdad Khanehkenari; Roy M Bremnes; Lill-Tove Busund Journal: PLoS One Date: 2017-07-25 Impact factor: 3.240
Authors: Tamkin Ahmadzada; Steven Kao; Glen Reid; Michael Boyer; Annabelle Mahar; Wendy A Cooper Journal: J Clin Med Date: 2018-06-15 Impact factor: 4.241
Authors: Theresa A Boyle; Farah K Khalil; Mari Mino-Kenudson; Gabriel L Sica; Andre L Moreira; Lynette M Sholl; Mirna Z Knight; Liping Zhang; James Saller; Marileila Varella-Garcia; Lynne D Berry; Heidi Chen; Kim E Ellison; Christopher J Rivard; Kelly Kugler; Ignacio I Wistuba; Junya Fujimoto; David J Kwiatkowski; Paul A Bunn; Mark G Kris; Eric B Haura; Fred R Hirsch Journal: Appl Immunohistochem Mol Morphol Date: 2020-10