nach oben

Virchows Archiv

Erschienen in:

13.01.2016 | Original Article

A significant subgroup of resectable gallbladder cancer patients has an HER2 positive status

verfasst von: Hiroshi Yoshida, Kazuaki Shimada, Tomoo Kosuge, Nobuyoshi Hiraoka

Erschienen in: Virchows Archiv | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

Abstract

Gallbladder cancer (GBC) has a poor prognosis, and new targeted therapeutic options are needed. We investigated the human epidermal growth factor receptor 2 (HER2) status and its clinicopathological significance in a large cohort of GBC patients. We assessed HER2 expression in a consecutive series of 211 GBC cases by immunohistochemistry (IHC), paying particular attention to intratumoral heterogeneity. HER2 gene amplification was analyzed by dual-color fluorescence in situ hybridization (FISH). An HER2 positive status was called when the IHC score was 3+ or when the IHC score was 2+, and FISH was positive. Correlations were analyzed between HER2 status and clinicopathological parameters including survival. The HER2 IHC score was 0 in 144 (68.2 %), 1+ in 28 (13.3 %), 2+ in 14 (6.6 %), and 3+ in 25 cases (11.8 %). In 20/39 (51 %) of the IHC 2+ and 3+ cases, the staining pattern was heterogeneous. In HER2 IHC score 2+ and 3+ cases, HER2 FISH was positive in 83 % (10/12) and 96 % (24/25), respectively. Altogether, 35/211 cases (16.6 %) were HER2 positive. There was no significant association between HER2 status and clinicopathological variables or survival. We identified a significant subgroup of HER2-positive GBC cases, for whom a clinical trial with anti-HER2 therapy might be considered.

Gallardo J, Rubio B, Villanueva L, Barajas O (2005) Gallbladder cancer, a different disease that needs individual trials. J Clin Oncol Off J Am Soc Clin Oncol 23(30):7753–7754. doi:10.1200/JCO.2005.02.7524, Author reply 7754–7755 CrossRef

Ferlay J SI, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F (2013) GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC cancer base no. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, Accessed 20 Dec 2014

McNamara MG, Metran-Nascente C, Knox JJ (2013) State-of-the-art in the management of locally advanced and metastatic gallbladder cancer. Curr Opin Oncol 25(4):425–431. doi:10.1097/CCO.0b013e3283620fd8 CrossRefPubMed

Moasser MM (2007) The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene 26(45):6469–6487. doi:10.1038/sj.onc.1210477 CrossRefPubMedPubMedCentral

Suzuki T, Takano Y, Kakita A, Okudaira M (1993) An immunohistochemical and molecular biological study of c-erbB-2 amplification and prognostic relevance in gallbladder cancer. Pathol Res Pract 189(3):283–292. doi:10.1016/S0344-0338(11)80511-X CrossRefPubMed

Kalekou H, Miliaras D (2004) Immunohistochemical study of microvessel density, CD44 (standard form), p53 protein and c-erbB2 in gallbladder carcinoma. J Gastroenterol Hepatol 19(7):812–818. doi:10.1111/j.1440-1746.2004.03357.xJGH3357 CrossRefPubMed

Matsuyama S, Kitajima Y, Sumi K, Mori D, Satoh T, Miyazaki K (2004) Gallbladder cancers rarely overexpress HER-2/neu, demonstrated by Hercep test. Oncol Rep 11(4):815–819PubMed

Nakazawa K, Dobashi Y, Suzuki S, Fujii H, Takeda Y, Ooi A (2005) Amplification and overexpression of c-erbB-2, epidermal growth factor receptor, and c-met in biliary tract cancers. J Pathol 206(3):356–365. doi:10.1002/path.1779 CrossRefPubMed

Chaube A, Tewari M, Garbyal RS, Singh U, Shukla HS (2006) Preliminary study of p53 and c-erbB-2 expression in gallbladder cancer in Indian patients manuscript ID: 8962091628764582. BMC Cancer 6:126. doi:10.1186/1471-2407-6-126 CrossRefPubMedPubMedCentral

10.

Puhalla H, Wrba F, Kandioler D, Lehnert M, Huynh A, Gruenberger T, Tamandl D, Filipits M (2007) Expression of p21(Wafl/Cip1), p57(Kip2) and HER2/neu in patients with gallbladder cancer. Anticancer Res 27(3B):1679–1684PubMed

11.

Harder J, Waiz O, Otto F, Geissler M, Olschewski M, Weinhold B, Blum HE, Schmitt-Graeff A, Opitz OG (2009) EGFR and HER2 expression in advanced biliary tract cancer. World J Gastroenterol 15(36):4511–4517CrossRefPubMedPubMedCentral

12.

Pignochino Y, Sarotto I, Peraldo-Neia C, Penachioni JY, Cavalloni G, Migliardi G, Casorzo L, Chiorino G, Risio M, Bardelli A, Aglietta M, Leone F (2010) Targeting EGFR/HER2 pathways enhances the antiproliferative effect of gemcitabine in biliary tract and gallbladder carcinomas. BMC Cancer 10:631. doi:10.1186/1471-2407-10-631 CrossRefPubMedPubMedCentral

13.

Shafizadeh N, Grenert JP, Sahai V, Kakar S (2010) Epidermal growth factor receptor and HER-2/neu status by immunohistochemistry and fluorescence in situ hybridization in adenocarcinomas of the biliary tree and gallbladder. Hum Pathol 41(4):485–492. doi:10.1016/j.humpath.2009.10.002 CrossRefPubMed

14.

Toledo C, Matus CE, Barraza X, Arroyo P, Ehrenfeld P, Figueroa CD, Bhoola KD, Del Pozo M, Poblete MT (2012) Expression of HER2 and bradykinin B(1) receptors in precursor lesions of gallbladder carcinoma. World J Gastroenterol 18(11):1208–1215. doi:10.3748/wjg.v18.i11.1208 CrossRefPubMedPubMedCentral

15.

Roa I, de Toro G, Schalper K, de Aretxabala X, Churi C, Javle M (2014) Overexpression of the HER2/neu gene: a new therapeutic possibility for patients with advanced gallbladder cancer. Gastrointest Cancer Res 7(2):42–48PubMedPubMedCentral

16.

Law LY (2012) Dramatic response to trastuzumab and paclitaxel in a patient with human epidermal growth factor receptor 2-positive metastatic cholangiocarcinoma. J Clin Oncol Off J Am Soc Clin Oncol 30(27):e271–e273. doi:10.1200/JCO.2012.42.3061 CrossRef

17.

Sorscher S (2013) Marked radiographic response of a HER-2-overexpressing biliary cancer to trastuzumab. Cancer Manag Res 9:1–3. doi:10.2147/CMAR.S55091 CrossRefPubMedPubMedCentral

18.

Kaseb A (2014) A phase II study trastuzumab (NSC 688097) in Her2/Neu positive cancer of the gallbladder or biliary tract (NCI 7756) http://clinicaltrials.gov/show/NCT00478140. Accessed 20 Dec 2014

19.

Hofmann M, Stoss O, Shi D, Buttner R, van de Vijver M, Kim W, Ochiai A, Ruschoff J, Henkel T (2008) Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 52(7):797–805. doi:10.1111/j.1365-2559.2008.03028.x CrossRefPubMed

20.

Yoshida H, Yamamoto N, Taniguchi H, Oda I, Katai H, Kushima R, Tsuda H (2014) Comparison of HER2 status between surgically resected specimens and matched biopsy specimens of gastric intestinal-type adenocarcinoma. Virchows Arch Int J Pathol 465(2):145–154. doi:10.1007/s00428-014-1597-3 CrossRef

21.

Kim YW, Huh SH, Park YK, Yoon TY, Lee SM, Hong SH (2001) Expression of the c-erb-B2 and p53 protein in gallbladder carcinomas. Oncol Rep 8(5):1127–1132PubMed

22.

Kaufman M, Mehrotra B, Limaye S, White S, Fuchs A, Lebowicz Y, Nissel-Horowitz S, Thomas A (2008) EGFR expression in gallbladder carcinoma in North America. Int J Med Sci 5(5):285–291CrossRefPubMedPubMedCentral

23.

Kumari N, Kapoor VK, Krishnani N, Kumar K, Baitha DK (2012) Role of C-erbB2 expression in gallbladder cancer. Indian J Pathol Microbiol 55(1):75–79. doi:10.4103/0377-4929.94862 CrossRefPubMed

24.

Muller BG, De Aretxabala X, Gonzalez Domingo M (2014) A review of recent data in the treatment of gallbladder cancer: what we know, what we do, and what should be done. Am Soc Clin Oncol Educ Book:e165-170. doi: 10.14694/EdBook_AM.2014.34.e165

25.

Chow NH, Huang SM, Chan SH, Mo LR, Hwang MH, Su WC (1995) Significance of c-erbB-2 expression in normal and neoplastic epithelium of biliary tract. Anticancer Res 15(3):1055–1059PubMed

26.

Vance GH, Barry TS, Bloom KJ, Fitzgibbons PL, Hicks DG, Jenkins RB, Persons DL, Tubbs RR, Hammond ME, College of American P (2009) Genetic heterogeneity in HER2 testing in breast cancer: panel summary and guidelines. Arch Pathol Lab Med 133(4):611–612. doi:10.1043/1543-2165-133.4.611 PubMed

27.

Lee HE, Park KU, Yoo SB, Nam SK, Park do J, Kim HH, Lee HS (2013) Clinical significance of intratumoral HER2 heterogeneity in gastric cancer. Eur J Cancer 49(6):1448–1457. doi:10.1016/j.ejca.2012.10.018 CrossRefPubMed

28.

Hanna W, Nofech-Mozes S, Kahn HJ (2007) Intratumoral heterogeneity of HER2/Neu in breast cancer—a rare event. Breast J 13(2):122–129. doi:10.1111/j.1524-4741.2007.00396.x CrossRefPubMed

29.

Chivukula M, Bhargava R, Brufsky A, Surti U, Dabbs DJ (2008) Clinical importance of HER2 immunohistologic heterogeneous expression in core-needle biopsies vs resection specimens for equivocal (immunohistochemical score 2+) cases. Mod Pathol Off J U S Can Acad Pathol, Inc 21(4):363–368. doi:10.1038/modpathol.3801021

30.

Rakha EA, Starczynski J, Lee AH, Ellis IO (2014) The updated ASCO/CAP guideline recommendations for HER2 testing in the management of invasive breast cancer: a critical review of their implications for routine practice. Histopathology 64(5):609–615. doi:10.1111/his.12357 CrossRefPubMed

31.

Kawamoto T, Krishnamurthy S, Tarco E, Trivedi S, Wistuba II, Li D, Roa I, Roa JC, Thomas MB (2007) HER receptor family: novel candidate for targeted therapy for gallbladder and extrahepatic bile duct cancer. Gastrointest Cancer Res 1(6):221–227PubMedPubMedCentral

32.

Hanna WM, Ruschoff J, Bilous M, Coudry RA, Dowsett M, Osamura RY, Penault-Llorca F, van de Vijver M, Viale G (2014) HER2 in situ hybridization in breast cancer: clinical implications of polysomy 17 and genetic heterogeneity. Mod Pathol Off J U S Can Acad Pathol, Inc 27(1):4–18. doi:10.1038/modpathol.2013.103

33.

Vranic S, Teruya B, Repertinger S, Ulmer P, Hagenkord J, Gatalica Z (2011) Assessment of HER2 gene status in breast carcinomas with polysomy of chromosome 17. Cancer 117(1):48–53. doi:10.1002/cncr.25580 CrossRefPubMed

Titel: A significant subgroup of resectable gallbladder cancer patients has an HER2 positive status
verfasst von: Hiroshi Yoshida
Kazuaki Shimada
Tomoo Kosuge
Nobuyoshi Hiraoka
Publikationsdatum: 13.01.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Virchows Archiv / Ausgabe 4/2016
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-015-1898-1

Neu im Fachgebiet Pathologie

Open Access 15.04.2024 | Biomarker | Schwerpunkt: Next Generation Pathology

Springer Medizin

A significant subgroup of resectable gallbladder cancer patients has an HER2 positive status

Abstract

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2016

In this issue

Funisitis is associated with adverse neonatal outcome in low-risk unselected deliveries at or near term

Consistency in recognizing microinvasion in breast carcinomas is improved by immunohistochemistry for myoepithelial markers

Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma

Tumour budding in colorectal cancer: what do we know and what can we do?

Intrafollicular Epstein-Barr virus-positive large B cell lymphoma. A variant of “germinotropic” lymphoproliferative disorder

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie