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01-10-2013 | Research

HER2 in Gastric Cancer: An Immunohistochemical Study on Tissue Microarrays and the Coressponding Whole-Tissue Sections with a Supplemental Fish Study

Authors: Gorana Gasljevic, Janez Lamovec, Juan Antonio Contreras, Vesna Zadnik, Mateja Blas, Slavko Gasparov

Published in: Pathology & Oncology Research | Issue 4/2013

Abstract

Since focal HER2 expression is an issue in GC, TMA construction from the paraffin-embedded surgically-obtained tissue may not reflect its real status. The aim of this study was to assess the HER2 status in tissue microarrays (TMAs) and the corresponding whole sections using HercepTest immunohistochemistry (IHC), and to correlate it and to assess the concordance of HER2 IHC and fluorescence in situ hybridization (FISH) in TMAs. Concordance of the HER2 expression status for 302 cases of gastric cancer using 9 paired TMAs was evaluated using a 2-mm core size and 305 corresponding whole sections. Concordance of the IHC and FISH HER2 status was compared. In addition,, the HER2 status was compared to clinicopathological characteristics and patients’ survival. Using the whole-section approach, HER2 over-expression was found in 25.2 % (HER2 3+ 6.6 %, HER2 2+ 18.7 %) of tumours. The overall concordance of IHC between the cores and the whole section was 84.9 %; 15.1 % of the tumours showed HER2 amplification. The overall concordance of IHC and FISH on cores was 75.7 %. The level of amplification correlated with the IHC score. Relationship between the intestinal and papillary types and tumour grade was observed for tumours with over-expression and amplification, whereas tumour location was related only to over-expression. There was a statistically significant difference in the overall survival of the patients, which was related to HER2 amplification. In conclusion, good concordance of the IHC HER2 results between tissue cores in TMA and whole sections, and excellent concordance of the IHC and FISH results on tissue cores was found. At least a part of the observed IHC HER2 heterogeneity could very likely be explained by fixation artifacts. With adequate fixation, a higher concordance of IHC HER2 between the cores and the whole sections can be expected. The TMA approach could enable an easier analysis of more than one representative tumour block.

Kamangar F, Dores GM, Anderson WF (2006) Patterns of cancer incidence, mortality and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24:2137–2150PubMedCrossRef

Cunningham SC, Kamangar F, Kim MP et al (2005) Survival after gastric adenocarcinoma resection: eighteen-year experience at single institution. J Gastrointest Surg 9:725–728

Fayçal J, Bessaguet C, Nousbaum JB et al (2005) Epidemiology and long term survival of gastric carcinoma in the French district of Finestere between 1984 and 1995. Gastroenterol Clin Biol 29:23–32PubMedCrossRef

Tsubono Y, Hisamichi S (2000) Screening for gastric cancer in Japan. Gastric Cancer 3:9–18PubMedCrossRef

Ohtsu A (2008) Chemotherapy for metastatic gastric cancer: past, present and future. Gastroenterology 43:256–264CrossRef

Menard S, Casalini P, Campiglio M, Pupa S, Agresti R, Tagliabue E (2001) HER2 overexpresion in various tumor types, focusing on its relationship to the development of invasive breast cancer. Ann Oncol 12:S15–S19PubMedCrossRef

Scholl S, Beuzeboc P, Pouillart P (2001) Targeting HER2 in other tumor types. Ann Oncol 12:S81–S87PubMedCrossRef

Ross JS, Slodkowska A, Symmans F, Pusztai L, Ravdin PM, Hortobagyi GN (2009) The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist 14:320–368PubMedCrossRef

Gravalos C, Jimeno A (2008) HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol 19:1523–1529PubMedCrossRef

10.

Jǿrgensen JT (2010) Targeted HER2 treatment in advanced gastric cancer. Oncology 78:26–33PubMedCrossRef

11.

Hofmann M, Stoss O, Shi D et al (2008) Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 52:797–805PubMedCrossRef

12.

Allgayer H, Babic R, Gruetzner KU, Tarabichi A, Schildberg FW, Heiss MM (2000) c-erbB-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumor-associated protease systems. J Clin Oncol 18(11):2201–2209PubMed

13.

Yano T, Toshihiko D, Ohtsu A et al (2006) Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol Rep 15:65–71PubMed

14.

Tanner M, Hollmen M, Junttila TT et al (2005) Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIα gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol 16:273–278PubMedCrossRef

15.

Lordick F, Bang YJ, Kang YK et al. (2007) HER2-positive advanced gastric cancer: similar HER2 positivity levels to breast cancer. P3541, ECCO 14, Barcelona, Spain, September

16.

Rüschoff J, Dietel M, Baretton G et al (2010) HER2 diagnostics in gastric cancer—guideline validation and development of standardized immunohistochemical testing. Virchows Arch 457(3):299–307PubMedCrossRef

17.

Park DI, Yun JW, Park JH et al (2006) HER2/neu amplification is an independent prognostic factor in gastric carcinoma. Dig Dis Sci 51:1371–1379PubMedCrossRef

18.

Drev P, Frkovic-Grazio S, Bracko M (2008) Tissue microarrays for routine diagnostic assessment of HER2 status in breast carcinoma. Appl Immunohistochem Mol Morphol 16(2):179–184PubMedCrossRef

19.

Grabsch H, Sivakumar S, Gray S, Gabbert HE, Müller W (2010) HER2 expression in gastric cancer: rare, heterogeneous and of no prognostic value—conclusions from 924 cases of two independent series. Cell Oncol 32:57–65PubMed

20.

Lee S, de Boer WB, Fermoyle S, Platten M, Kumarasinghe MP (2011) Human epidermal growth factor receptor 2 testing in gastric carcinoma: issues related to heterogeneity in biopsies and resections. Histopathology 59:832–840PubMedCrossRef

21.

Kunz PL, Mojtahed A, Fisher G et al (2012) HER2 expression in gastric and gastroesophageal junction adenocarcinoma in a US population: clinicopathologic analysis with proposed approach to HER2 assessment. Appl Immunohistochem Mol Morphol 20(1):13–24PubMedCrossRef

22.

Park SY, Hwang HS, Park HJ et al (2012) Comprehensive analysis of HER2 expression and gene amplification in gastric cancers using immunohistochemistry and in situ hybridization: which scoring system should we use? Hum Pathol 43(3):413–422PubMedCrossRef

23.

Marx AH, Simon R, Sauter G (2010) HER-2 amplification is highly homogeneous in gastric cancer-reply. Hum Pathol 41:305–306CrossRef

24.

Moelans CB, Milne AN, Morsink FH, Offerhaus GA, van Diest PJ (2011) Low frequency of HER2 amplification and overexpression in early onset gastric cancer. Cell Oncol 34:89–95CrossRef

25.

Penault-Llorca F, Bilous M, Dowset M et al (2009) Emerging technologies for assesing HER2 amplification. Am J Clin Pathol 132:539–548PubMedCrossRef

26.

Simon R, Mirlacher M, Sauter G (2003) Tissue microarrays in cancer diagnosis. Expert Rev Mol Diagn 3:421–430PubMedCrossRef

27.

Sauter G, Mirlacher M (2002) Tissue microarrys for predictive molecular pathology. J Clin Pathol 55:575–576PubMedCrossRef

28.

Bang YJ, Van Cutsem E, Feyereislova A et al (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastroesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376:687–697PubMedCrossRef

29.

Bang YJ, Chung HC, Xu JM et al. (2009) Pathological features of advanced gastric cancer: relationship to human epidermal growth factor receptor 2 positivity in the global screeening programme of the ToGA trial. J Clin Oncol 27(Suppl.15s); Abstract 4556

30.

Barros-Silva JD, Leitão D, Afonso L et al (2009) Association of ERBB2 gene status with histopathological parameters and disease specific survival in gastric carcinoma patients. BJC 100:487–493PubMedCrossRef

31.

Kim MA, Jung EJ, Lee SH et al (2007) Evaluation of HER2 gene status in gastric carcinoma using immunohistochemistry, fluorescence in situ hybridization and real-time quantitative polymerase chain reaction. Hum Pathol 38:1386–1393PubMedCrossRef

32.

Zheng HC, Li X, Hara T, Masuda S et al (2008) Mixed-type gastric carcinomas exhibit more aggressive features and indicate the histogenesis of carcinomas. Virchows Arch 452:525–534PubMedCrossRef

Title: HER2 in Gastric Cancer: An Immunohistochemical Study on Tissue Microarrays and the Coressponding Whole-Tissue Sections with a Supplemental Fish Study
Authors: Gorana Gasljevic
Janez Lamovec
Juan Antonio Contreras
Vesna Zadnik
Mateja Blas
Slavko Gasparov
Publication date: 01-10-2013
Publisher: Springer Netherlands
Published in: Pathology & Oncology Research / Issue 4/2013
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-013-9654-9

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