A survival guide to HER2 testing in gastric/gastroesophageal junction carcinoma

2019 ◽  
Vol 90 (1) ◽  
pp. 44-54 ◽  
Author(s):  
Duminda Subasinghe ◽  
Nathan Acott ◽  
Marian Priyanthi Kumarasinghe
Keyword(s):  
Gastroesophageal Junction ◽  
Her2 Testing ◽  
Gastroesophageal Junction Carcinoma

HER2 testing in gastric and gastroesophageal junction adenocarcinomas

2014 ◽  
Vol 20 (6) ◽  
pp. 247-256
Author(s):  
Jason Y. Park ◽  
Paul J. Zhang
Keyword(s):  
Gastroesophageal Junction ◽  
Her2 Testing

Significance of accurate HER2 testing as a new biomarker in advanced gastric cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 106-106
Author(s):  
Tetsuya Kusumoto ◽  
Hajime Ohtsu ◽  
Hiroyuki Kawano ◽  
Koji Ando ◽  
Satoshi Ida ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Gastroesophageal Junction ◽  
Tumor Biology ◽  
Japanese Patients ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Her2 Testing ◽  
Gastroesophageal Junction Cancer ◽  
Her2 Heterogeneity

106 Background: The Trastuzumab for Gastric Cancer (ToGA) study is the first international trial to include Japanese patients with human epidermal growth factor 2 (HER2)-positive advanced or recurrent gastric or gastroesophageal junction cancer, which demonstrated that trastuzumab plus chemotherapy improved overall survival in the overall population (hazard ratio 0.74). HER2 testing in gastric cancer differs from testing in breast cancer due to inherent differences in tumor biology; gastric cancer more frequently shows HER2 heterogeneity and incomplete membrane staining. The aim of the present study was to evaluate the frequency of HER2-positive cases by application of the standard criteria in Japanese patients with advanced gastric cancer (AGC) and to investigate the relationships between HER2 expression and therapeutic responses. Methods: A total of 199 tumor samples were assessed for HER2 expression both by immunohistochemistry (IHC) and HER2 amplification by fluorescence in situ hybridization (FISH). HER2-positive status was defined as IHC2+ and FISH-positive or IHC3+. Objective responses were evaluated in the patients with AGC who were treated with chemotherapy plus trastuzumab or chemotherapy alone based on the HER2 expression status. Results: HER2-positive tumors were identified in 12 patients (5.5%), less than 28.1% in the Japanese subgroup analyses of ToGA study. The positive rates varied with histological type; 14%, 5.3% and 0.95% in the well, moderately and poorly differentiated adenocarcinoma, respectively. Although high concordance between the results of IHC and FISH in all samples was found, IHC2+ samples retested here showed FISH-negative. Of all 10 patients with AGC, 3 patients with HER2-positive tumor were treated with capecitabine/cisplatin plus trastuzumab, and partial response was found in 2 cases; response rates were 67%. Conclusions: Specific consideration and scoring modification are required before embarking on HER2 testing in gastric cancer. Accurate and reliable HER2 testing and scoring will allow appropriate selection of patients eligible for treatment with trastuzumab.

False-negative rate for HER2 testing in 738 gastric and gastroesophageal junction cancers (GEC) from two global randomized clinical trials.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 16-16 ◽  
Author(s):  
David Cunningham ◽  
Manish A. Shah ◽  
Dustin Smith ◽  
Maria Zoudilova ◽  
Stephen Paul Hack ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Gastroesophageal Junction ◽  
False Negative ◽  
False Negative Rate ◽  
Intestinal Morphology ◽  
Her2 Positive ◽  
Her2 Testing ◽  
Negative Rate ◽  
Clinically Significant

16 Background: False-negative HER2 testing in GEC may deny patients the benefit of HER2-targeted therapy. The aim of this study is to estimate the false-negative rate for HER2 testing in GEC and to evaluate predictive factors that might be used to select patients for re-testing. Methods: Two clinical trials conducted in patients with HER2-negative GEC were conducted by Genentech (NCT01662869 and NCT01590719). Information on local HER2 results was collected and testing was repeated centrally by immunohistochemistry (IHC; Ventana, 4B5 antibody) and FISH. HER2 positivity was determined using published criteria (Mod Pathol 2012;25:637). Results: Of 1,189 patients screened, 738 GECs were HER2 negative by local testing and had central results available. Twenty-nine patients (3.9%, 95% confidence interval [CI] 2.5–5.3) were locally HER2 negative, but centrally HER2 positive. The cases showed a wide geographic distribution, a mixture of biopsies (n=19) and resections (n=10), and a mixture of gastric cancer (n=20) and GEC (n=9). All false-negative cases were centrally confirmed to be Lauren’s intestinal (n=25) or mixed (n=4) morphology; amongst intestinal/mixed GEC, the false-negative rate was 6.4% (95% CI 4.1–8.6). Detailed local testing results were available for 25 cases, of which 21 cases showed local IHC scores of 0 or 1+ but were centrally IHC 2+/FISH positive (n=17) or IHC 3+ (n=4). The remaining 4 cases were locally HER2 IHC 2+, FISH negative, but centrally IHC 2+, FISH positive. Conclusions: A clinically significant false-negative rate of 6.4% was observed for HER2 testing in GEC (intestinal/mixed type). Several measures might improve the accuracy of HER2 testing, including running FISH and IHC on all cases, carefully evaluating internal positive controls, improving the education of pathologists, and retesting cases with mixed or intestinal morphology. Clinical trial information: NCT01590719 and NCT01662869.

scholarly journals A multi-center phase II study of oxaliplatin, irinotecan, and capecitabine in advanced gastric/gastroesophageal junction carcinoma

2008 ◽  
Vol 63 (5) ◽  
pp. 851-857 ◽  
Author(s):  
Joanna M. Brell ◽  
Smitha S. Krishnamurthi ◽  
Milind Javle ◽  
Joel Saltzman ◽  
Ira Wollner ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Gastroesophageal Junction ◽  
Gastroesophageal Junction Carcinoma

HER2 testing in esophageal adenocarcinoma (EAC) using parallel tissue-based methods.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 2-2 ◽  
Author(s):  
Harry H. Yoon ◽  
Qian Shi ◽  
William R. Sukov ◽  
Christopher A. Sattler ◽  
Anne E. Wiktor ◽  
...  
Keyword(s):  
Gene Amplification ◽  
Predictive Value ◽  
Gastroesophageal Junction ◽  
Her2 Amplification ◽  
Her2 Protein ◽  
Her2 Testing ◽  
Blinded Manner ◽  
Testing Algorithm ◽  
Background Testing

2 Background: Testing for HER2 in EAC has become routine given its ability to predict benefit from HER2-targeted therapy. HER2 protein analysis by immunohistochemistry (IHC) is more rapid and generally less expensive than assessment of gene amplification by fluorescence in situ hybridization (FISH). However, the accuracy of IHC for predicting HER2 amplification has not been examined in a large EAC cohort. Methods: Surgical EAC specimens were examined from 675 patients who underwent curative resection at a single institution without preoperative therapy. Tumors were located in the esophagus (47%) or gastroesophageal junction (53%); most were node-positive (73%). Every tumor was evaluated by IHC in parallel with FISH in a blinded manner using FDA-approved assays. A consensus IHC score was determined by 2 pathologists using tumor-specific criteria (negative, 0 or 1+; equivocal, 2+; positive, 3+). Gene amplification by FISH was defined as a HER2/CEP17ratio ≥ 2. Results: HER2 amplification was detected in 89% of IHC 3+ cases, 13% of IHC 2+ cases, and 4% of IHC 0-1+ cases (Table). Accordingly, using FISH as the reference standard, the positive predictive value (PPV) of a positive IHC test (3+) was 89% (79/89 [95% CI 82%-95%]), and the negative predictive value of a negative IHC test (0-1+) was 96% (401/417 [94%-98%]). Importantly, the PPV of an equivocal IHC score (2+) for detecting HER2 amplification was 13% (22/169 [8%-18%]). Conclusions: In the largest study to date comparing HER2 testing methods in EAC, a negative IHC result (0 or 1+) nearly excludes the presence of gene amplification by FISH. Whereas a positive IHC result (3+) strongly predicts for the presence of amplification, an equivocal IHC result (2+) is a weak predictor. These findings in EAC support a HER2 testing algorithm where IHC is used for initial screening and FISH testing is restricted to cases with equivocal IHC results. [Table: see text]

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