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Published in: Gastric Cancer 2/2016

Open Access 01-04-2016 | Original Article

Five biopsy specimens from the proximal part of the tumor reliably determine HER2 protein expression status in gastric cancer

Authors: Naoyuki Tominaga, Takuji Gotoda, Megumi Hara, Matthew D. Hale, Takayoshi Tsuchiya, Jun Matsubayashi, Shin Kono, Chika Kusano, Takao Itoi, Kazuma Fujimoto, Fuminori Moriyasu, Heike I. Grabsch

Published in: Gastric Cancer | Issue 2/2016

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Abstract

Background

National guidelines recommend trastuzumab for treatment of patients with metastatic HER2-positive gastric cancer (GC). There is currently no guideline indicating the number of biopsy specimens and the location from which they should be obtained to reliably determine the human epidermal growth factor receptor 2 (HER2) status in GC. The aim of this pilot study was (a) to quantify HER2-positive tumor cells in different tumor regions to assess the spatial heterogeneity of HER2 expression and (b) to establish the required number of biopsy specimens and the location from which they should be obtained within the tumor to achieve concordance between HER2 expression status in the biopsy specimens and the resection specimen.

Methods

HER2 expression was quantified in six different regions of 24 HER2-positive GC and in six virtual biopsy specimens from different luminal regions. Intratumoral regional heterogeneity and concordance between HER2 status in the biopsy specimens and the resection specimen were analyzed.

Results

HER2-positive cells were more frequent in the luminal tumor surface compared with deeper layers (p < 0.001). GCs with differentiated histological features were more commonly HER2 positive (p < 0.001). Assessment of HER2 expression status in five biopsy specimens was sufficient to achieve 100 % concordance between the biopsy specimens and the resection specimen.

Conclusions

This is the first study to suggest preferential HER2 positivity at the luminal surface in GC and to establish a minimum number of biopsy specimens needed to obtain a biopsy HER2 result which is identical to that from the whole tumor. Our study suggests that HER2 testing in five tumor-containing endoscopic biopsy specimens from the proximal (oral) part of the tumor is advisable. The results from this pilot study require validation in a prospective study.
Literature
1.
go back to reference Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase no. 11. Lyon: International Agency for Research on Cancer; 2013. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase no. 11. Lyon: International Agency for Research on Cancer; 2013.
3.
go back to reference Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. 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;376:687–97. doi:10.1016/s0140-6736(10)61121-x.CrossRefPubMed Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. 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;376:687–97. doi:10.​1016/​s0140-6736(10)61121-x.CrossRefPubMed
4.
go back to reference Waddell T, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D. Gastric cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):57–63. doi:10.1093/annonc/mdt344.CrossRef Waddell T, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D. Gastric cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):57–63. doi:10.​1093/​annonc/​mdt344.CrossRef
5.
go back to reference Ajani JA, Bentrem DJ, Besh S, D’Amico TA, Das P, Denlinger C, et al. Gastric cancer, version 2.2013: featured updates to the NCCN guidelines. J Natl Compr Cancer Netw. 2013;11(5):531–46. Ajani JA, Bentrem DJ, Besh S, D’Amico TA, Das P, Denlinger C, et al. Gastric cancer, version 2.2013: featured updates to the NCCN guidelines. J Natl Compr Cancer Netw. 2013;11(5):531–46.
7.
go back to reference Tanner M, Hollmén M, Junttila TT, Kapanen AI, Tommola S, Soini Y, et al. Amplification of HER2 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.CrossRefPubMed Tanner M, Hollmén M, Junttila TT, Kapanen AI, Tommola S, Soini Y, et al. Amplification of HER2 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.CrossRefPubMed
9.
go back to reference Kunz PL, Mojtahed A, Fisher GA, Ford JM, Chang DT, Balise RR, et al. HER2 expression in gastric and gastroesophageal junction adenocarcinoma in a US population: clinicopathologic analysis with proposed approach to HER2 assessment. Appl Immunohistochem Mol Morphol. 2012;20(1):13–24. doi:10.1097/PAI.0b013e31821c821c.CrossRefPubMed Kunz PL, Mojtahed A, Fisher GA, Ford JM, Chang DT, Balise RR, et al. HER2 expression in gastric and gastroesophageal junction adenocarcinoma in a US population: clinicopathologic analysis with proposed approach to HER2 assessment. Appl Immunohistochem Mol Morphol. 2012;20(1):13–24. doi:10.​1097/​PAI.​0b013e31821c821c​.CrossRefPubMed
10.
go back to reference Janjigian YY, Werner D, Pauligk C, Steinmetz K, Kelsen DP, Jager E, et al. Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA international collaborative analysis. Ann Oncol. 2012;23(10):2656–62. doi:10.1093/annonc/mds104.CrossRefPubMed Janjigian YY, Werner D, Pauligk C, Steinmetz K, Kelsen DP, Jager E, et al. Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA international collaborative analysis. Ann Oncol. 2012;23(10):2656–62. doi:10.​1093/​annonc/​mds104.CrossRefPubMed
11.
go back to reference Grabsch H, Sivakumar S, Gray S, Gabbert HE, Müller W. HER2 expression in gastric cancer: rare, heterogeneous and of no prognostic value––conclusions from 924 cases of two independent series. Cell Oncol. 2010;32(1–2):57–65. doi:10.3233/CLO-2009-0497.PubMedPubMedCentral Grabsch H, Sivakumar S, Gray S, Gabbert HE, Müller W. HER2 expression in gastric cancer: rare, heterogeneous and of no prognostic value––conclusions from 924 cases of two independent series. Cell Oncol. 2010;32(1–2):57–65. doi:10.​3233/​CLO-2009-0497.PubMedPubMedCentral
13.
go back to reference Yan B, Yau EX, Choo SN, Ong CW, Yong KJ, Pang B, et al. Dual-colour HER2/chromosome 17 chromogenic in situ hybridisation assay enables accurate assessment of HER2 genomic status in gastric cancer and has potential utility in HER2 testing of biopsy samples. J Clin Pathol. 2011;64(10):880–3. doi:10.1136/jclinpath-2011-200009.CrossRefPubMed Yan B, Yau EX, Choo SN, Ong CW, Yong KJ, Pang B, et al. Dual-colour HER2/chromosome 17 chromogenic in situ hybridisation assay enables accurate assessment of HER2 genomic status in gastric cancer and has potential utility in HER2 testing of biopsy samples. J Clin Pathol. 2011;64(10):880–3. doi:10.​1136/​jclinpath-2011-200009.CrossRefPubMed
14.
go back to reference Yano T, Doi T, Ohtsu A, Boku N, Hashizume K, Nakanishi M, 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(1):65–71.PubMed Yano T, Doi T, Ohtsu A, Boku N, Hashizume K, Nakanishi M, 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(1):65–71.PubMed
15.
go back to reference Yang J, Luo H, Li Y, Li J, Cai Z, Su X, et al. Intratumoral heterogeneity determines discordant results of diagnostic tests for human epidermal growth factor receptor (HER) 2 in gastric cancer specimens. Cell Biochem Biophys. 2012;62(1):221–8. doi:10.1007/s12013-011-9286-1.CrossRefPubMed Yang J, Luo H, Li Y, Li J, Cai Z, Su X, et al. Intratumoral heterogeneity determines discordant results of diagnostic tests for human epidermal growth factor receptor (HER) 2 in gastric cancer specimens. Cell Biochem Biophys. 2012;62(1):221–8. doi:10.​1007/​s12013-011-9286-1.CrossRefPubMed
18.
go back to reference Sobin LH, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumors. 7th ed. Chichester: Wiley; 2009. Sobin LH, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumors. 7th ed. Chichester: Wiley; 2009.
20.
go back to reference Ieni A, Barresi V, Giuffrè G, Caruso RA, Lanzafame S, Villari L, et al. HER2 status in advanced gastric carcinoma: a retrospective multicentric analysis from Sicily. Oncol Lett. 2013;6(6):1591–4.PubMedPubMedCentral Ieni A, Barresi V, Giuffrè G, Caruso RA, Lanzafame S, Villari L, et al. HER2 status in advanced gastric carcinoma: a retrospective multicentric analysis from Sicily. Oncol Lett. 2013;6(6):1591–4.PubMedPubMedCentral
21.
go back to reference Inokuchi K, Sugimachi K. Growth patterns of gastric cancer. In: Nishi M, Ichikawa H, Nakajima T, Maruyama K, Tahara E, editors. Gastric cancer. Tokyo: Springer Japan; 1993. p 88–101. Inokuchi K, Sugimachi K. Growth patterns of gastric cancer. In: Nishi M, Ichikawa H, Nakajima T, Maruyama K, Tahara E, editors. Gastric cancer. Tokyo: Springer Japan; 1993. p 88–101.
Metadata
Title
Five biopsy specimens from the proximal part of the tumor reliably determine HER2 protein expression status in gastric cancer
Authors
Naoyuki Tominaga
Takuji Gotoda
Megumi Hara
Matthew D. Hale
Takayoshi Tsuchiya
Jun Matsubayashi
Shin Kono
Chika Kusano
Takao Itoi
Kazuma Fujimoto
Fuminori Moriyasu
Heike I. Grabsch
Publication date
01-04-2016
Publisher
Springer Japan
Published in
Gastric Cancer / Issue 2/2016
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-015-0502-3

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