Assessment the of Amplification HER-2/neu Gene by Chromogenic In Situ Hybridization (CISH) Compared to Immunohistochemistry (IHC) Method in Gastric Cancer

Authors

1 Student Research Committee, Gastrointestinal and Fatty Liver Research Center, Faculty of Medical Sciences,Mashhad University of Medical Sciences,Mashhad, IR Iran

2 Fellowship of Molecular Pathology and Cytogenetics, ImamReza Hospital,Mashhad University of Medical Sciences,Mashhad, IR Iran

3 Fellow of Molecular Pathology and Cytogenetics, Shiraz University of Medical Sciences, Shiraz, Iran

4 Professor of Pathology, ImamReza Hospital,Mashhad University of Medical Sciences,Mashhad, IR Iran

5 Resident of pathology, ImamReza Hospital,Mashhad University of Medical Sciences,Mashhad, IR Iran

Abstract

Abstract Background: Gastric cancer has a highmortality rate and often has a poor treatment outcome. The HER2/neu gene target therapy has been known as a potential way for treatment. Objectives: The goal of our study was assessment the relation between chromogenic in situ hybridization (CISH) and immunohis- tochemistry (IHC)methods in determining the best diagnosticmethod for gastric cancer. Methods: In this historical cohort study, 50 gastric cancer samples were analyzed by CISH and IHC. The relation between clinical- pathological parameters of HER2/neu was also analyzed. Alive patients were followed from 2009 through 2012 for the main out- comes (mortality). The results of these twomethods, in terms of sex, age, tumor size, grading, staging, tumor location,metaplasia, presence of necrosis and ulceration, vascular invasion, the TNM system, mucin or signet producing adenocarcinoma cells and pa- tient survival rates were compared. Results: There was no significant difference between IHC and CISH regarding the sex, age, tumor size, grading, staging, tumor lo- cation,metaplasia, presence of necrosis and ulceration, vascular invasion, the TNMsystem,mucin or signet producing adenocarci- noma cells and patient survival rates. Comparison of TNMscores by these twomethods showed no significant relationship between IHC and staging, but a statistically significant difference between CISH and different N staging, (P < 0.05) was assessed. Conclusions: Comparison between IHC and CISH showed the only significant relationship between CISH and different N staging. Therefore, low amplified CISH was a better diagnosticmethod for gastric cancer, compared to low expression in IHC.

Keywords


  1. Brenner H, Rothenbacher D, Arndt V. Epidemiology of stomach cancer. Methods Mol Biol. 2009;472:467–77. doi: 10.1007/978-1-60327-492- 0_23. [PubMed: 19107449].
  2. Mousavi SM, Gouya MM, Ramazani R, Davanlou M, Hajsadeghi N, Seddighi Z. Cancer incidence and mortality in Iran. Ann Oncol. 2009;20(3):556–63. doi: 10.1093/annonc/mdn642. [PubMed: 19073863].
  3. Malekzadeh R, Derakhshan MH, Malekzadeh Z. Gastric cancer in Iran: epidemiology and risk factors. Arch Iran Med. 2009;12(6):576–83. [PubMed: 19877751].
  4. Bozzetti C, Negri FV, Lagrasta CA, Crafa P, Bassano C, Tamagnini I, et al. Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma. Br J Cancer. 2011;104(9):1372–6. doi: 10.1038/bjc.2011.121. [PubMed: 21487407].
  5. Hofmann M, Stoss O, Shi D, Buttner R, van de Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study.Histopathology. 2008;52(7):797–805. doi: 10.1111/j.1365- 2559.2008.03028.x. [PubMed: 18422971].
  6. Carter WB, Hoying JB, Boswell C, Williams SK. HER2/neu overexpression induces endothelial cell retraction. Int J Cancer. 2001;91(3):295–9. [PubMed: 11169950].
  7. Tanner M, Gancberg D, Di Leo A, Larsimont D, Rouas G, Piccart MJ, et al. Chromogenic in Situ Hybridization. Am J Pathol. 2000;157(5):1467–72. doi: 10.1016/s0002-9440(10)64785-2.
  8. Reisenbichler ES, Horton D, Rasco M, Andea A, Hameed O. Evaluation of dual immunohistochemistry and chromogenic in situ hybridization for HER2 on a single section. Am J Clin Pathol. 2012;137(1):102–10. doi: 10.1309/AJCPLNHINN9O6YSF. [PubMed: 22180483].
  9. Tanner M, Hollmen M, Junttila TT, Kapanen AI, Tommola S, Soini Y, et al. Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol. 2005;16(2):273–8. doi: 10.1093/annonc/mdi064. [PubMed: 15668283].
  10. Madrid MA, Lo RW. Chromogenic in situ hybridization (CISH): a novel alternative in screening archival breast cancer tissue samples for HER-2/neu status. Breast Cancer Res. 2004;6(5):R593–600. doi: 10.1186/bcr915. [PubMed: 15318940].
  11. Lee KE, Lee HJ, Kim YH, Yu HJ, Yang HK, Kim WH, et al. Prognostic significance of p53, nm23, PCNA and c-erbB-2 in gastric cancer. Jpn J Clin Oncol. 2003;33(4):173–9. [PubMed: 12810831].
  12. Aoyagi K, Kohfuji K, Yano S, Murakami N, Miyagi M, Takeda J, et al. Evaluation of the epidermal growth factor receptor (EGFR) and c-erbB-2 in superspreading-type and penetrating-type gastric carcinoma. Kurume Med J. 2001;48(3):197–200. [PubMed: 11680933].
  13. Thor A. HER2–a discussion of testing approaches in the USA.Ann Oncol. 2001;12 Suppl 1:S101–7. [PubMed: 11521714].
  14. Paik S, Bryant J, Tan-Chiu E, Romond E, Hiller W, Park K, et al. Real-world performance of HER2 testing–National Surgical Adjuvant Breast and Bowel Project experience. J Natl Cancer Inst. 2002;94(11):852–4. [PubMed: 12048273].
  15. Roche PC, Suman VJ, Jenkins RB, Davidson NE, Martino S, Kaufman PA, et al. Concordance between local and central laboratory HER2 testing in the breast intergroup trial N9831. J Natl Cancer Inst. 2002;94(11):855– 7. [PubMed: 12048274].
  16. Fitzgibbons PL, Page DL, Weaver D, Thor AD, Allred DC, Clark GM, et al. Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med. 2000;124(7):966–78. doi: 10.1043/0003-9985(2000)124lt;0966:PFIBCgt;2.0.CO;2. [PubMed: 10888772].
  17. Hoang MP, Sahin AA, Ordonez NG, Sneige N. HER-2/neu gene amplification compared with HER-2/neu protein overexpression and interobserver reproducibility in invasive breast carcinoma. Am J Clin Pathol. 2000;113(6):852–9. doi: 10.1309/VACP-VLQA-G9DX-VUDF. [PubMed: 10874886].
  18. Ridolfi RL, Jamehdor MR, Arber JM. HER-2/neu testing in breast carcinoma: a combined immunohistochemical and fluorescence in situ hybridization approach. Mod Pathol. 2000;13(8):866–73. doi: 10.1038/modpathol.3880154. [PubMed: 10955453].
  19. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20(3):719–26. doi: 10.1200/JCO.2002.20.3.719. [PubMed: 11821453].
  20. Vincent-Salomon A, MacGrogan G, Couturier J, Arnould L, Denoux Y, Fiche M, et al. Calibration of immunohistochemistry for assessment of HER2 in breast cancer: results of the French multicentre GEFPICS study. Histopathology. 2003;42(4):337–47. [PubMed: 12653945].
  21. Zhao J, Wu R, Au A, Marquez A, Yu Y, Shi Z. Determination of HER2 gene amplification by chromogenic in situ hybridization (CISH) in archival breast carcinoma. Mod Pathol. 2002;15(6):657–65. doi: 10.1038/modpathol.3880582. [PubMed: 12065780].
  22. Kato N, Itoh H, Serizawa A, Hatanaka Y, Umemura S, Osamura RY. Evaluation of HER2 gene amplification in invasive breast cancer using a dual-color chromogenic in situ hybridization (dual CISH). Pathol Int. 2010;60(7):510–5. doi: 10.1111/j.1440-1827.2010.02553.x. [PubMed: 20594272]. 23. Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008;19(9):1523–9. doi: 10.1093/annonc/mdn169. [PubMed: 18441328].
  23. Park DI, Yun JW, Park JH, Oh SJ, Kim HJ, Cho YK, et al. HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci. 2006;51(8):1371–9. doi: 10.1007/s10620-005-9057-1. [PubMed: 16868827].
  24. Todorovic-Rakovic N, Jovanovic D, Neskovic-Konstantinovic Z, Nikolic-Vukosavljevic D. Comparison between immunohistochemistry and chromogenic in situ hybridization in assessing HER-2 status in breast cancer. Pathol Int. 2005;55(6):318–23. doi: 10.1111/j.1440- 1827.2005.01831.x. [PubMed: 15943788].
  25. Jacquemier J, Spyratos F, Esterni B, Mozziconacci MJ, Antoine M, Arnould L, et al. SISH/CISH or qPCR as alternative techniques to FISH for determination of HER2 amplification status on breast tumors core needle biopsies: a multicenter experience based on 840 cases. BMC Cancer. 2013;13:351. doi: 10.1186/1471-2407-13-351. [PubMed: 23875536].