BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is likely overexpressed and/or amplified in locally advanced gastric cancer with extensive (bulky N2 or paraaortic) lymph node metastasis, and patients may benefit from treatment with anti-HER2 antibodies. This study evaluated the frequency of HER2 overexpression and amplification in The Japanese Gastric Cancer Association (JGCA)-N3 and JGCA-bulky N2 tumors and the correlation between HER2 status and survival. METHODS: HER2 status was assessed using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in tumor tissue samples from 89 patients with gastric adenocarcinoma enrolled in the phase II JCOG0001 and JCOG0405 trials. HER2 positivity was defined as IHC3+ or IHC2+ with confirmatory FISH results. RESULTS: Of the 89 tumor samples, 24 (27 %) showed HER2 positivity, including 16 scored as IHC3+ and 8 as IHC2+ and FISH positive. Multivariate analysis showed that the HER2 positivity rate was significantly higher in evaluable differentiated tumors than in undifferentiated tumors [18/44 (40.9 %) vs. 5/42 (11.9 %)]. Although the apparent OS curve of HER2 positive was superior to that of HER2 negative patients, HER2 status was not a statistically significant prognostic factor in multivariate analysis. CONCLUSION: The HER2 positivity rate was relatively high in patients with JGCA-bulky N2 and JGCA-N3 gastric adenocarcinoma, suggesting that HER2 evaluation is essential to select the therapeutic regimen for neoadjuvant chemotherapy for this group of patients.
BACKGROUND:Human epidermal growth factor receptor 2 (HER2) is likely overexpressed and/or amplified in locally advanced gastric cancer with extensive (bulky N2 or paraaortic) lymph node metastasis, and patients may benefit from treatment with anti-HER2 antibodies. This study evaluated the frequency of HER2 overexpression and amplification in The Japanese Gastric Cancer Association (JGCA)-N3 and JGCA-bulky N2 tumors and the correlation between HER2 status and survival. METHODS:HER2 status was assessed using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in tumor tissue samples from 89 patients with gastric adenocarcinoma enrolled in the phase II JCOG0001 and JCOG0405 trials. HER2 positivity was defined as IHC3+ or IHC2+ with confirmatory FISH results. RESULTS: Of the 89 tumor samples, 24 (27 %) showed HER2 positivity, including 16 scored as IHC3+ and 8 as IHC2+ and FISH positive. Multivariate analysis showed that the HER2 positivity rate was significantly higher in evaluable differentiated tumors than in undifferentiated tumors [18/44 (40.9 %) vs. 5/42 (11.9 %)]. Although the apparent OS curve of HER2 positive was superior to that of HER2 negative patients, HER2 status was not a statistically significant prognostic factor in multivariate analysis. CONCLUSION: The HER2 positivity rate was relatively high in patients with JGCA-bulky N2 and JGCA-N3 gastric adenocarcinoma, suggesting that HER2 evaluation is essential to select the therapeutic regimen for neoadjuvant chemotherapy for this group of patients.
Authors: Ian Smith; Marion Procter; Richard D Gelber; Sébastien Guillaume; Andrea Feyereislova; Mitch Dowsett; Aron Goldhirsch; Michael Untch; Gabriella Mariani; Jose Baselga; Manfred Kaufmann; David Cameron; Richard Bell; Jonas Bergh; Robert Coleman; Andrew Wardley; Nadia Harbeck; Roberto I Lopez; Peter Mallmann; Karen Gelmon; Nicholas Wilcken; Erik Wist; Pedro Sánchez Rovira; Martine J Piccart-Gebhart Journal: Lancet Date: 2007-01-06 Impact factor: 79.321
Authors: M Tanner; M Hollmén; T T Junttila; A I Kapanen; S Tommola; Y Soini; H Helin; J Salo; H Joensuu; E Sihvo; K Elenius; J Isola Journal: Ann Oncol Date: 2005-02 Impact factor: 32.976
Authors: Martine J Piccart-Gebhart; Marion Procter; Brian Leyland-Jones; Aron Goldhirsch; Michael Untch; Ian Smith; Luca Gianni; Jose Baselga; Richard Bell; Christian Jackisch; David Cameron; Mitch Dowsett; Carlos H Barrios; Günther Steger; Chiun-Shen Huang; Michael Andersson; Moshe Inbar; Mikhail Lichinitser; István Láng; Ulrike Nitz; Hiroji Iwata; Christoph Thomssen; Caroline Lohrisch; Thomas M Suter; Josef Rüschoff; Tamás Suto; Victoria Greatorex; Carol Ward; Carolyn Straehle; Eleanor McFadden; M Stella Dolci; Richard D Gelber Journal: N Engl J Med Date: 2005-10-20 Impact factor: 91.245
Authors: Harry H Yoon; Qian Shi; William R Sukov; Mark A Lewis; Christopher A Sattler; Anne E Wiktor; Tsung-Teh Wu; Robert B Diasio; Robert B Jenkins; Frank A Sinicrope Journal: J Clin Oncol Date: 2012-09-17 Impact factor: 44.544
Authors: Roberto de Moraes Cordts Filho; Paulo Kassab; Laura Carolina Lopez Claro; Mabel Tatty de Medeiros Fracassi; Patrícia Colombo-Souza; Daniel Kenji Fukuhara; Fábio Rodrigues Thuler; Wilson Rodrigues de Freitas Junior; Elias Jirjoss Ilias; Carlos Alberto Malheiros Journal: ScientificWorldJournal Date: 2016-12-25