Heterogeneous amplification of ERBB2 in primary lesions is responsible for the discordant ERBB2 status of primary and metastatic lesions in gastric carcinoma

Abstract

Kim M A, Lee H‐J, Yang H‐K, Bang Y‐J & Kim W H (2011) Histopathology 59 , 822–831 Heterogeneous amplification of ERBB2 in primary lesions is responsible for the discordant ERBB2 status of primary and metastatic lesions in gastric carcinoma Aims: To determine the extent of HER2 homogeneity/heterogeneity in primary versus metastatic gastric carcinoma (GC). Materials and results: The human epidermal growth factor receptor 2 (HER2) status in primary and metastatic lesions was evaluated by immunohistochemistry (IHC) and fluorescence in‐situ hybridization (FISH). Four separate cohorts consisting of primary GC alone or primary GC paired with metastatic lesions were examined. In the FISH analysis of 325 primary GCs, eight cases (2.5%) showed amplification with a heterogeneous pattern, whereas 27 cases (8.3%) showed amplification with a homogeneous pattern, and in this cohort the discordant:concordant FISH ratio based on examination of three different areas in each primary lesion was 0.30:1. FISH testing using 250 paired primary and metastatic lesions revealed seven cases (2.8%) with discordant amplification. In metastatic disease positive conversion occurred in six cases (2.4%), whereas negative conversion happened in one case (0.4%). The discordant:concordant ratio of primary versus secondary lesions was 0.23:1. When the seven discordant cases were re‐evaluated using whole sections of primary GCs, six showed a heterogeneous pattern of amplification. Conclusions: These findings suggest that the discordant HER2 amplification observed in metastatic lesions is explained substantially by heterogeneity within primary tumours.

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References 25

1. 1.

   Akiyama T, Sudo C, Ogawara H, Toyoshima K, Yamamoto T. The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science. 1986;232:1644-1646.

   Not in our library10.1126/science.3012781

2. 2.

   Xu YH, Richert N, Ito S, Merlino GT, Pastan I. Characterization of epidermal growth factor receptor gene expression in malignant and normal human cell lines. Proc. Natl Acad. Sci. USA. 1984;81:7308-7312.

   Not in our library10.1073/pnas.81.23.7308

3. 3.

   Ross JS, Fletcher DA. ERBB2/neu (c-erb-B2) gene and protein in breast cancer. Am. J. Clin. Pathol. 1999;112:S53-S67.

   Not in our library

4. 4.

   Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 2001;344:783-792.

   Not in our library10.1056/nejm200103153441101

5. 5.

   Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N. Engl. J. Med. 2005;353:1659-1672.

   Not in our library10.1056/nejmoa052306

6. 6.

   Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N. Engl. J. Med. 2005;353:1673-1684.

   Not in our library10.1056/nejmoa052122

7. 7.

   Nakajima M, Sawada H, Yamada Y, et al. The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer. 1999;85:1894-1902.

   Not in our library10.1002/(sici)1097-0142(19990501)85:9<1894::aid-cncr3>3.0.co;2-j

8. 8.

   Kim MA, Jung EJ, Lee HS, et al. Evaluation of ERBB2 gene status in gastric carcinoma using immunohistochemistry, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction. Hum. Pathol. 2007;38:1386-1393.

   Not in our library10.1016/j.humpath.2007.02.005

9. 9.

   Yano T, Doi T, Ohtsu A, et al. Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol. Rep. 2006;15:65-71.

   Not in our library

10. 10.

    Kimura M, Tsuda H, Morita D, et al. A proposal for diagnostically meaningful criteria to classify increased epidermal growth factor receptor and c-erbB-2 gene copy numbers in gastric carcinoma based on correlation of fluorescence in situ hybridization and immunohistochemical measurements. Virchows Arch. 2004;445:255-262.

    Not in our library10.1007/s00428-004-1048-7

11. 11.

    Tanner M, Hollmen M, Junttila TT, et al. Amplification of ERBB2 in gastric carcinoma: association with topoisomerase IIα gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann. Oncol. 2005;16:273-278.

    Not in our library10.1093/annonc/mdi064

12. 12.

    Van Cutsem E, Kang Y, Chung H, et al. Efficacy results from the ToGA trial: a phase III study of trastuzumab added to standard chemotherapy in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer. J. Clin. Oncol. 2009;27:18S.

    Not in our library

13. 13.

    Santinelli A, Pisa E, Stramazzotti D, Fabris G. ERBB2 status discrepancy between primary breast cancer and metastatic sites. Impacts on target therapy. Int. J. Cancer. 2008;122:999-1004.

    Not in our library10.1002/ijc.23051

14. 14.

    Vincent-Salomon A, Jouve M, Genin P, et al. HER2 status in patients with breast carcinoma is not modified selectively by preoperative chemotherapy and is stable during the metastatic process. Cancer. 2002;94:2169-2173.

    Not in our library10.1002/cncr.10456

15. 15.

    Simon R, Nocito A, Hubscher T, et al. Patterns of ERBB2/neu amplification and overexpression in primary and metastatic breast cancer. J. Natl Cancer Inst. 2001;93:1141-1146.

    Not in our library10.1093/jnci/93.15.1141

16. 16.

    Gong Y, Booser DJ, Sneige N. Comparison of ERBB2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma. Cancer. 2005;103:1763-1769.

    Not in our library10.1002/cncr.20987

17. 17.

    Gancberg D, Di Leo A, Cardoso F, et al. Comparison of ERBB2 status between primary breast cancer and corresponding distant metastatic sites. Ann. Oncol. 2002;13:1036-1043.

    Not in our library10.1093/annonc/mdf252

18. 18.
    Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease · 2005

    No notice
19. 19.
    HER2 expression in breast cancer primary tumours and corresponding metastases. Original data and literature review · 2004

    No notice
20. 20.

    Marx AH, Tharun L, Muth J, et al. ERBB2 amplification is highly homogenous in gastric cancer. Hum. Pathol. 2009;40:769-777.

    Not in our library10.1016/j.humpath.2008.11.014

21. 21.

    Kim JH, Kim MA, Lee HS, Kim WH. Comparative analysis of protein expressions in primary and metastatic gastric carcinomas. Hum. Pathol. 2009;40:314-322.

    Not in our library10.1016/j.humpath.2008.07.013

22. 22.

    Hoffmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: result from a validation study. Histopathology. 2008;52:797-805.

    Not in our library10.1111/j.1365-2559.2008.03028.x

23. 23.

    Cottu PH, Asselah J, Lae M, et al. Intratumoral heterogeneity of HER2/neu expression and its consequences for the management of advanced breast cancer. Ann. Oncol. 2008;19:596-597.

    Not in our library10.1093/annonc/mdn021

24. 24.

    Kunitomo K, Inoue S, Ichihara F, et al. A case of metastatic breast cancer with outgrowth of HER2-negative cells after eradication of HER2-positive cells by humanized anti-HER2 monoclonal antibody (trastuzumab) combined with docetaxel. Hum. Pathol. 2004;35:379-381.

    Not in our library10.1016/j.humpath.2003.05.003

25. 25.

    Wolff AC, Hammon MEH, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists Guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J. Clin. Oncol. 2007;25:118-145.

    Not in our library10.1200/jco.2006.09.2775

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