Mechanisms of acquired resistance to trastuzumab-based treatment in gastric cancer are largely unknown. In this study, we analyzed 22 pairs of tumor samples taken at baseline and post-progression in patients receiving chemotherapy and trastuzumab for advanced HER2-positive [immunohistochemistry (IHC) 3+ or 2+ with in-situ hybridization (ISH) amplification] gastric or gastroesophageal cancers. Strict clinical criteria for defining acquired trastuzumab resistance were adopted. Loss of HER2 positivity and loss of HER2 over-expression were defined as post-trastuzumab IHC score <3+ and absence of ISH amplification, and IHC "downscoring" from 2+/3+ to 0/1+, respectively. HER2 IHC was always performed, while ISH was missing in 3 post-progression samples. Patients with initial HER2 IHC score 3+ and 2+ were 14 (64%) and 8 (36%), respectively. Loss of HER2 positivity and HER2 over-expression was observed in 32 and 32% samples, respectively. The chance of HER2 loss was not associated with any of the baseline clinicopathological variables. The only exception was in patients with initial IHC score 2+ versus 3+, for both endpoints of HER2 positivity (80 vs. 14%; p=0.008) and HER2 over-expression (63 vs. 14%; p=0.025). As already shown in breast cancer, loss of HER2 may be observed also in gastric cancers patients treated with trastuzumab-based chemotherapy in the clinical practice. This phenomenon may be one of the biological reasons explaining the failure of anti-HER2 second-line strategies in initially HER2-positive disease.
HER2 loss in HER2-positive gastric or gastroesophageal cancer after trastuzumab therapy : Implication for further clinical research / F. Pietrantonio, M. Caporale, F. Morano, M. Scartozzi, A. Gloghini, F. De Vita, E. Giommoni, L. Fornaro, G. Aprile, D. Melisi, R. Berenato, A. Mennitto, C.C. Volpi, M.M. Laterza, V. Pusceddu, L. Antonuzzo, E. Vasile, E. Ongaro, F. Simionato, F. de Braud, V. Torri, M. Di Bartolomeo. - In: INTERNATIONAL JOURNAL OF CANCER. - ISSN 0020-7136. - 139:12(2016 Dec), pp. 2859-2864.
|Titolo:||HER2 loss in HER2-positive gastric or gastroesophageal cancer after trastuzumab therapy : Implication for further clinical research|
PIETRANTONIO, FILIPPO (Corresponding)
|Parole Chiave:||gastric cancer; HER2; HER2 loss; resistance; trastuzumab; medicine (all); oncology; cancer research|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
|Data di pubblicazione:||dic-2016|
|Data ahead of print / Data di stampa:||ago-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/ijc.30408|
|Appare nelle tipologie:||01 - Articolo su periodico|
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