Summary
This Australian human epidermal growth factor receptor 2 (HER2) testing program aimed
to analyse >800 cases tested in a coordinated setting to further evaluate the criteria
to establish HER2 status in advanced gastric and gastro-oesophageal junction (GOJ)
cancer. Heterogeneity, and minimum number of biopsy fragments for reliable HER2 assessment
were also examined in a subset of samples.
Five laboratories tested 891 samples referred to determine HER2 status for potential
anti-HER2 treatment. Cancer site, specimen type (endoscopic biopsy/resection/metastases),
immunohistochemistry (IHC) score, HER2 gene and CEP17 copy number (CN) and HER2:CEP17
ratios were recorded. Samples were derived from stomach (53.1%), GOJ (28.2%) or metastases
(18.5%). IHC for HER2 and dual probe HER2:CEP17 in situ hybridisation (ISH) were performed in parallel. A stringent definition (SD) of HER2
positivity was used (IHC2+/3+ plus CN>6 and ratio>2) and compared with other published
criteria.
HER2 positive rate was 13.9% (114/820) by SD, and 12.9–16.0% using other definitions.
There was higher concordance between IHC and HER2 CN by ISH than with ratio. The HER2
positive rate was significantly higher in GOJ samples than others (p = 0.03) and in endoscopic biopsies than resections (p = 0.047). In a subset of 98 positive cases, 39 (39.8%) showed heterogeneity, and
in 282 endoscopic biopsies positivity rate plateaued at five tumour fragments, suggesting
this is the minimum number of biopsies that should be examined.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to PathologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Cited 18 May 2014. http://globocan.iarc.fr/.
- Estimates of global cancer prevalence for 27 sites in the adult population in 2008.Int J Cancer. 2013; 132: 1133-1145
- HER2-positive gastric cancer.Gastric Cancer. 2014; 17: 1-12
- Prognostic role of human epidermal growth factor receptor in gastric cancer: a systematic review and meta-analysis.Arch Med Res. 2013; 44: 380-389
- Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients.Br J Cancer. 2009; 100: 487-493
- Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial.Lancet. 2010; 376: 687-697
- Gastric HER2 Testing Study (GaTHER): an evaluation of gastric/gastroesophageal junction cancer testing accuracy in Australia.Am J Surg Pathol. 2012; 36: 577-582
- Level of HER2 gene amplification predicts response and overall survival in HER2-positive advanced gastric cancer treated with trastuzumab.J Clin Oncol. 2013; 31: 4445-4452
- HER2 testing in gastric cancer: a practical approach.Mod Pathol. 2012; 25: 637-650
- Human epidermal growth factor receptor 2 testing in gastric cancer: recommendations of an Asia-Pacific task force.Asia Pac J Clin Oncol. 2014; 10: 297-307
- HER2 testing in malignant effusions of metastatic gastric carcinoma: is it feasible?.Diagn Cytopathol. 2015; 43: 80-85
- HER2 status in gastric/gastro-oesophageal junctional cancers: should determination of gene amplification by SISH use HER2 copy number or HER2: CEP17 ratio?.Pathology. 2014; 46: 184-187
- Human epidermal growth factor receptor 2 testing in gastric carcinoma: issues related to heterogeneity in biopsies and resections.Histopathology. 2011; 59: 832-840
- HER2 in situ hybridization in breast cancer: clinical implications of polysomy 17 and genetic heterogeneity.Mod Pathol. 2014; 27: 4-18
- Concordance of HER2 expression in paired primary and metastatic sites of gastric and gastro-oesophageal junction cancers.Pathology. 2015; 47: 641-646
- Matched biopsy and resection specimens of gastric and gastroesophageal adenocarcinoma show high concordance in HER2 status.Hum Pathol. 2014; 45: 970-975
- Biomarker testing for breast, lung, and gastroesophageal cancers at NCI designated cancer centers.J Natl Cancer Inst. 2014; 106dju256
- Establishment of the Australian in situ hybridization program for the assessment of HER2 amplification in breast cancer: a model for the introduction of new biomarkers into clinical practice.Diagn Mol Pathol. 2010; 19: 187-193
- Assessment of a HER2 scoring system for gastric cancer: results from a validation study.Histopathology. 2008; 52: 797-805
Roche Products Pty Limited. Australian Herceptin (trastuzumab) Product Information. 2016; cited 24 Oct 2016. http://www.guildlink.com.au/gc/ws/ro/pi.cfm?product=ropherce10315.
- Media Release. FDA approves Herceptin for HER2-positive metastatic stomach cancer.21 Oct 2010 (cited 7 Dec 2015)
- European Herceptin (trastuzumab) Product Information.2013 (Cited 7 Dec 2015)
- HER2/neu testing for anti-HER2-based therapies in patients with unresectable and/or metastatic gastric cancer.J Clin Pathol. 2012; 65: 751-757
- HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing.Virchows Arch. 2010; 457: 299-307
- HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology.J Clin Oncol. 2017; 35: 446-464
- Public Summary Document. Application No. 1163.1-Testing for HER2 status in gastric cancer for access to trastuzumab.2015 (cited 16 Feb 2017)
- Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes.Nat Med. 2015; 21: 449-456
- Activating HER2 mutations in HER2 gene amplification negative breast cancer.Cancer Discov. 2013; 3: 224-237
- HER2 gene mutations in non-small cell lung carcinomas: concurrence with Her2 gene amplification and Her2 protein expression and phosphorylation.Lung Cancer. 2015; 87: 14-22
- HER2 missense mutations have distinct effects on oncogenic signaling and migration.Proc Natl Acad Sci USA. 2015; 112: E6205-E6214
- A potential pitfall in evaluating HER2 immunohistochemistry for gastric signet ring cell carcinomas.Pathology. 2017; 49: 38-43
- Prognostic significance of signet ring gastric cancer.J Clin Oncol. 2012; 30: 3493-3498
- Targeted HER2 treatment in advanced gastric cancer.Oncology. 2010; 78: 26-33
- HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target.Ann Oncol. 2008; 19: 1523-1529
- HER2 expression and relevant clinicopathological features in gastric and gastroesophageal junction adenocarcinoma in a Chinese population.Diagn Pathol. 2013; 8: 76
- Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma.Br J Cancer. 2011; 104: 1372-1376
- How many biopsy fragments will be necessary to assess HER2 status for gastric cancer?.J Clin Oncol. 2012; 30: 40
- Ideal number of biopsy tumor fragments for predicting HER2 status in gastric carcinoma resection specimens.Oncotarget. 2015; 6: 38372-38380
Article info
Publication history
Published online: August 17, 2017
Accepted:
May 21,
2017
Received in revised form:
May 15,
2017
Received:
February 27,
2017
Identification
Copyright
© 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.
