HER2 in solid tumors: more than 10 years under the microscope; where are we now?

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

• 1 Popescu NC, King CR, Kraus MH. Localization of the human erbB-2 gene on normal and rearranged chromosomes 17 to bands q12–21.32. Genomics 4, 362–366 (1989).
  Medline CASGoogle Scholar
• 2 Graus-Porta D, Beerli RR, Daly JM, Hynes NE. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J. 16, 1647–1655 (1997).
  Medline CASGoogle Scholar
• 3 Tzahar E, Waterman H, Chen X et al. A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor. Mol. Cell Biol. 16, 5276–5287 (1996).
  Medline CASGoogle Scholar
• 4 Lenferink AE, Pinkas-Kramarski R, van de Poll ML et al. Differential endocytic routing of homo- and hetero-dimeric ErbB tyrosine kinases confers signaling superiority to receptor heterodimers. EMBO J. 17, 3385–3397 (1998).
  Medline CASGoogle Scholar
• 5 Gajria D, Chandarlapaty S. HER2-amplified breast cancer: mechanisms of trastuzumab resistance and novel targeted therapies. Expert Rev. Anticancer Ther. 11, 263–275 (2011).
  Medline CASGoogle Scholar
• 6 Miller TW, Rexer BN, Garrett JT, Arteaga CL. Mutations in the phosphatidylinositol 3-kinase pathway: role in tumor progression and therapeutic implications in breast cancer. Breast Cancer Res. 13, 224 (2011).
  Medline CASGoogle Scholar
• 7 Mohd Sharial MS, Crown J, Hennessy BT. Overcoming resistance and restoring sensitivity to HER2-targeted therapies in breast cancer. Ann. Oncol. 23, 3007–3016 (2012).
  Medline CASGoogle Scholar
• 8 Herter-Sprie GS, Greulich H, Wong KK. Activating mutations in ERBB2 and their impact on diagnostics and treatment. Front. Oncol. 3, 86 (2013).
  MedlineGoogle Scholar
• 9 Ross JS, Fletcher JA, Bloom KJ et al. Targeted therapy in breast cancer: the HER-2/neu gene and protein. Mol. Cell. Proteomics 3, 379–398 (2004).
  Medline CASGoogle Scholar
• 10 COSMIC: Catalogue of Somatic Mutations in Cancer. ERBB2. http://cancer.sanger.ac.uk/cosmic/gene/overview?ln=ERBB2
  Google Scholar
• 11 Slamon DJ, Godolphin W, Jones LA et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244, 707–712 (1989).
  Medline CASGoogle Scholar
• 12 Tapia C, Glatz K, Novotny H et al. Close association between HER-2 amplification and overexpression in human tumors of non-breast origin. Mod. Pathol. 20, 192–198 (2007).
  Medline CASGoogle Scholar
• 13 Scholl S, Beuzeboc P, Pouillart P. Targeting HER2 in other tumor types. Ann. Oncol. 12(Suppl. 1), S81–S87 (2001).
  MedlineGoogle Scholar
• 14 Slamon DJ, Clark GM, Wong SG et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235, 177–182 (1987).
  Medline CASGoogle Scholar
• 15 Tanner M, Hollmén M, Junttila TT 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. 16, 273–278 (2005).
  Medline CASGoogle Scholar
• 16 Bang YJ, Van Cutsem E, Feyereislova 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. 376, 687–697 (2010).•• First clinical trial showing trastuzumab efficacy in HER2-positive advanced gastric cancer, leading to the introduction of HER2 test in routine practice for gastric cancer. 
  Medline CASGoogle Scholar
• 17 Ooi A, Takehana T, Li X et al. Protein overexpression and gene amplification of HER-2 and EGFR in colorectal cancers: an immunohistochemical and fluorescent in situ hybridization study. Mod. Pathol. 17, 895–904 (2004).
  Medline CASGoogle Scholar
• 18 Al-Kuraya K, Novotny H, Bavi P et al. HER2, TOP2A, CCND1, EGFR and C-MYC oncogene amplification in colorectal cancer. J. Clin. Pathol 60, 768–772 (2007).
  Medline CASGoogle Scholar
• 19 Herreros-Villanueva M, Rodrigo M, Claver M et al. KRAS, BRAF, EGFR and HER2 gene status in a Spanish population of colorectal cancer. Mol. Biol. Rep. 38, 1315–1320 (2011).
  Medline CASGoogle Scholar
• 20 Cornolti G, Ungari M, Morassi ML et al. Amplification and overexpression of HER2/neu gene and HER2/neu protein in salivary duct carcinoma of the parotid gland. Arch. Otolaryngol. Head Neck Surg. 133, 1031–1036 (2007).
  MedlineGoogle Scholar
• 21 Lae M, Couturier J, Oudard S et al. Assessing HER2 gene amplification as a potential target for therapy in invasive urothelial bladder cancer with a standardized methodology: results in 1005 patients. Ann. Oncol. 21, 815–819 (2010).
  Medline CASGoogle Scholar
• 22 Tuefferd M, Couturier J, Penault-Llorca F et al. HER2 status in ovarian carcinomas: a multicenter GINECO study of 320 patients. PLoS ONE 2, e1138 (2007).
  MedlineGoogle Scholar
• 23 Vermeij J, Teugels E, Bourgain C et al. Genomic activation of the EGFR and HER2–neu genes in a significant proportion of invasive epithelial ovarian cancers. BMC Cancer 8, 3 (2008).
  MedlineGoogle Scholar
• 24 Pellegrini C, Falleni M, Marchetti A et al. HER-2/Neu alterations in non-small cell lung cancer: a comprehensive evaluation by real time reverse transcription-PCR, fluorescence in situ hybridization, and immunohistochemistry. Clin. Cancer Res. 9, 3645–3652 (2003).
  Medline CASGoogle Scholar
• 25 Langer CJ, Stephenson P, Thor A, Vangel M, Johnson DH. Trastuzumab in the treatment of advanced non-small-cell lung cancer: is there a role? Focus on Eastern Cooperative Oncology Group study 2598. J. Clin. Oncol. 22, 1180–1187 (2004).
  Medline CASGoogle Scholar
• 26 Grob TJ, Kannengiesser I, Tsourlakis MC et al. Heterogeneity of ERBB2 amplification in adenocarcinoma, squamous cell carcinoma and large cell undifferentiated carcinoma of the lung. Mod. Pathol. 25, 1566–1573 (2012).
  Medline CASGoogle Scholar
• 27 Jimenez RE, Hussain M, Bianco FJ Jr et al. Her-2/neu overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic significance and comparative analysis in primary and metastatic tumors. Clin. Cancer Res. 7, 2440–2447 (2001).
  Medline CASGoogle Scholar
• 28 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. 344, 783–792 (2001).• First clinical trial showing trastuzumab efficacy in HER2-positive advanced breast cancer, leading to the introduction of HER2 test in routine practice for metastatic breast cancer. 
  Medline CASGoogle Scholar
• 29 Smith I, Procter M, Gelber RD et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369, 29–36 (2007).
  Medline CASGoogle Scholar
• 30 ClincalTrials.gov. www.clincaltrials.gov
  Google Scholar
• 31 Valabrega G, Montemurro F, Aglietta M. Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer. Ann. Oncol. 18, 977–984 (2007).
  Medline CASGoogle Scholar
• 32 Ross JS, Slodkowska EA, Symmans WF et al. The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist 14, 320–368 (2009).
  Medline CASGoogle Scholar
• 33 Gampenrieder SP, Rinnerthaler G, Greil R. neoadjuvant chemotherapy and targeted therapy in breast cancer: past, present, and future. J. Oncol. 2013, 732047 (2013).
  MedlineGoogle Scholar
• 34 Miller TW, Rexer BN, Garrett JT, Arteaga CL. Mutations in the phosphatidylinositol 3-kinase pathway: role in tumor progression and therapeutic implications in breast cancer. Breast Cancer Res. 13, 224 (2011).
  Medline CASGoogle Scholar
• 35 Chandarlapaty S, Sakr RA, Giri D et al. Frequent mutational activation of the PI3K–AKT pathway in trastuzumab-resistant breast cancer. Clin. Cancer Res. 18, 6784–6791 (2012).
  Medline CASGoogle Scholar
• 36 Hanker AB, Pfefferle AD, Balko JM et al. Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies. Proc. Natl Acad. Sci. USA 110, 14372–14377 (2013).
  Medline CASGoogle Scholar
• 37 Rexer BN, Arteaga CL. Optimal targeting of HER2–PI3K signaling in breast cancer: mechanistic insights and clinical implications. Cancer Res. 73, 3817–3820 (2013).
  Medline CASGoogle Scholar
• 38 Harbeck N. American Society of Clinical Oncology highlights 2013: breast cancer and gynecological malignancies. Future Oncol. 9, 1433–1436 (2013).
  CASGoogle Scholar
• 39 Kim SY, Kim HP, Kim YJ et al. Trastuzumab inhibits the growth of human gastric cancer cell lines with HER2 amplification synergistically with cisplatin. Int. J. Oncol. 32, 89–95 (2008).
  MedlineGoogle Scholar
• 40 Chung C, Lam MS. Pertuzumab for the treatment of human epidermal growth factor receptor type 2-positive metastatic breast cancer. Am. J. Health Syst. Pharm. 70, 1579–1587 (2013).
  Medline CASGoogle Scholar
• 41 Geyer CE, Forster J, Lindquist D et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N. Engl. J. Med. 355, 2733–2743 (2006).
  Medline CASGoogle Scholar
• 42 Ulhoa-Cintra A, Greenberg L, Geyer CE. The emerging role of lapatinib in HER2-positive breast cancer. Curr. Oncol. Rep. 10, 10–17 (2008).
  Medline CASGoogle Scholar
• 43 Goss PE, Smith IE, O’Shaughnessy J et al. Adjuvant lapatinib for women with early-stage HER2-positive breast cancer: a randomised, controlled, Phase 3 trial. Lancet Oncol. 14, 88–96 (2013).
  Medline CASGoogle Scholar
• 44 Agus DB, Akita RW, Fox WD et al. Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell. 2, 127–137 (2002).
  Medline CASGoogle Scholar
• 45 Smith MB, Reardon J, Olson EM. Pertuzumab for the treatment of patients with previously untreated HER2-positive metastatic breast cancer. Drugs Today (Barc.) 48, 713–722 (2012).
  Medline CASGoogle Scholar
• 46 Langdon SP, Cameron DA. Pertuzumab for the treatment of metastatic breast cancer. Expert Rev. Anticancer Ther. 13, 907–918 (2013).
  Medline CASGoogle Scholar
• 47 Metzger Filho O, Winer EP, Krop I. Pertuzumab: optimizing HER2 blockade. Clin. Cancer Res. 19, 5552–5556 (2013).
  Medline CASGoogle Scholar
• 48 Blumenthal GM, Scher NS, Cortazar P et al. First FDA approval of dual anti-HER2 regimen: pertuzumab in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer. Clin. Cancer Res. 19, 4911–4916 (2013).
  Medline CASGoogle Scholar
• 49 Khasraw M, Bell R. Primary systemic therapy in HER2-amplified breast cancer: a clinical review. Expert Rev. Anticancer Ther. 12, 1005–1013 (2012).
  Medline CASGoogle Scholar
• 50 Nielsen DL, Kümler I, Palshof JA et al. Efficacy of HER2-targeted therapy in metastatic breast cancer. Monoclonal antibodies and tyrosine kinase inhibitors. Breast 22, 1–12 (2013).
  MedlineGoogle Scholar
• 51 Opdam FL, Guchelaar HJ, Beijnen JH, Schellens JH. Lapatinib for advanced or metastatic breast cancer. Oncologist 17, 536–542 (2012).
  Medline CASGoogle Scholar
• 52 Blackwell KL, Burstein HJ, Storniolo AM et al. Randomized study of lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J. Clin. Oncol. 28, 1124–1130 (2010).
  Medline CASGoogle Scholar
• 53 Lewis Phillips GD, Li G, Dugger DL et al. Targeting HER2-positive breast cancer with trastuzumab–DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 68, 9280–9290 (2008).
  Medline CASGoogle Scholar
• 54 Ballantyne A, Dhillon S. Trastuzumab emtansine: first global approval. Drugs 73, 755–765 (2013).
  Medline CASGoogle Scholar
• 55 Goldenberg MV. Pharmaceutical approval update. PT 38, 246–258 (2013).
  MedlineGoogle Scholar
• 56 Krop IE, Beeram M, Modi S et al. Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer. J. Clin. Oncol. 28, 2698–2704 (2010).
  Medline CASGoogle Scholar
• 57 Bighin C, Pronzato P, Del Mastro L. Trastuzumab emtansine in the treatment of HER-2-positive metastatic breast cancer patients. Future Oncol. 9, 955–957 (2013).
  CASGoogle Scholar
• 58 Barginear MF, John V, Budman DR. Trastuzumab–DM1: a clinical update of the novel antibody–drug conjugate for HER2-overexpressing breast cancer. Mol. Med. 18, 1473–1479 (2013).
  MedlineGoogle Scholar
• 59 Barok M, Tanner M, Köninki K et al. Trastuzumab–DM1 is highly effective in preclinical models of HER2-positive gastric cancer. Cancer Lett. 306, 171–179 (2011).
  Medline CASGoogle Scholar
• 60 Pazo Cid RA, Antón A. Advanced HER2-positive gastric cancer: current and future targeted therapies. Crit Rev. Oncol. Hematol. 85, 350–362 (2013).
  MedlineGoogle Scholar
• 61 Slamon DJ, Clark GM, Wong SG et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235, 177–182 (1987).
  Medline CASGoogle Scholar
• 62 Winstanley J, Cooke T, Murray GD et al. The long term prognostic significance of c-erbB-2 in primary breast cancer. Br. J. Cancer 63, 447–450 (1991).
  Medline CASGoogle Scholar
• 63 Pauletti G, Godolphin W, Press MF et al. Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization. Oncogene 13, 63–72 (1996).
  Medline CASGoogle Scholar
• 64 Wolff AC, Hammond ME, 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. 25, 118–145 (2007).
  Medline CASGoogle Scholar
• 65 Wolff AC, Hammond ME, Hicks DG et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update. J. Clin. Oncol. 31, 3997–4013 (2013).•• American Society of Clinical Oncology/College of American Pathologists updated guidelines for HER2 testing in breast cancer.
  MedlineGoogle Scholar
• 66 Hanna WM, Rüschoff J, Bilous M et al. HER2 in situ hybridization in breast cancer: clinical implications of polysomy 17 and genetic heterogeneity. Mod. Pathol. (2013) (In Press). •• Review with useful summaries of published papers concerning HER2 genetic heterogeneity and polysomy.
  Google Scholar
• 67 Marchiò C, Lambros MB, Gugliotta P et al. Does chromosome 17 centromere copy number predict polysomy in breast cancer? A fluorescence in situ hybridization and microarray-based CGH analysis. J. Pathol. 219, 16–24 (2009).
  Medline CASGoogle Scholar
• 68 Yeh IT, Martin MA, Robetorye RS et al. Clinical validation of an array CGH test for HER2 status in breast cancer reveals that polysomy 17 is a rare event. Mod. Pathol. 22, 1169–1175 (2009).
  Medline CASGoogle Scholar
• 69 Troxell ML, Bangs CD, Lawce HJ et al. Evaluation of Her-2/neu status in carcinomas with amplified chromosome 17 centromere locus. Am. J. Clin. Pathol. 126, 709–716 (2006).
  Medline CASGoogle Scholar
• 70 Egervari K, Kosa C, Szollosi Z. Impact of chromosome 17 centromere region assessment on HER2 status reported in breast cancer. Pathol. Res. Pract. 207, 468–471 (2011).
  Medline CASGoogle Scholar
• 71 Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer. http://cgap.nci.nih.gov/Chromosomes/Mitelman •• Large database collecting all the published tumor karyotypes.
  Google Scholar
• 72 Vranic S, Teruya B, Repertinger S, Ulmer P, Hagenkord J, Gatalica Z. Assessment of HER2 gene status in breast carcinomas with polysomy of chromosome 17. Cancer 117, 48–53 (2011).
  MedlineGoogle Scholar
• 73 Zhu X, Lu Y, Lu H et al. Genetic alterations and protein expression of HER2 and chromosome 17 polysomy in breast cancer. Hum. Pathol. 42, 1499–1504 (2011).
  Medline CASGoogle Scholar
• 74 Burrell RA, Juul N, Johnston SR et al. Targeting chromosomal instability and tumour heterogeneity in HER2-positive breast cancer. J. Cell Biochem. 111, 782–790 (2010).
  Medline CASGoogle Scholar
• 75 Orsaria M, Khelifa S, Buza N, Kamath A, Hui P. Chromosome 17 polysomy: correlation with histological parameters and HER2NEU gene amplification. J. Clin. Pathol. 66, 1070–1075 (2013).
  MedlineGoogle Scholar
• 76 Walker RA, Bartlett JM, Dowsett M et al. HER2 testing in the UK: further update to recommendations. J. Clin. Pathol. 61, 818–824 (2008).
  Medline CASGoogle Scholar
• 77 Dowsett M, Bartlett J, Ellis IO et al. Correlation between immunohistochemistry (HercepTest) and fluorescence in situ hybridization (FISH) for HER-2 in 426 breast carcinomas from 37 centres. J. Pathol. 199, 418–423 (2003).
  Medline CASGoogle Scholar
• 78 Sauter G, Lee J, Bartlett JM et al. Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J. Clin. Oncol. 27, 1323–1333 (2009).
  Medline CASGoogle Scholar
• 79 Ohlschlegel C, Zahel K, Kradolfer D et al. HER2 genetic heterogeneity in breast carcinoma. J. Clin. Pathol. 64, 1112–1116 (2011).
  Medline CASGoogle Scholar
• 80 Allison KH, Dintzis SM, Schmidt RA. Frequency of HER2 heterogeneity by fluorescence in situ hybridization according to CAP expert panel recommendations: time for a new look at how to report heterogeneity. Am. J. Clin. Pathol. 136, 864–871 (2011).
  MedlineGoogle Scholar
• 81 Chang MC, Malowany JI, Mazurkiewicz J et al. ‘Genetic heterogeneity’ in HER2/neu testing by fluorescence in situ hybridization: a study of 2,522 cases. Mod. Pathol. 25, 683–688 (2012).
  Medline CASGoogle Scholar
• 82 Shafi H, Astvatsaturyan K, Chung F, Mirocha J, Schmidt M, Bose S. Clinicopathological significance of HER2/neu genetic heterogeneity in HER2/neu non-amplified invasive breast carcinomas and its concurrent axillary metastasis. J. Clin. Pathol. 66, 649–654 (2013).
  Medline CASGoogle Scholar
• 83 Starczynski J, Atkey N, Connelly Y et al. HER2 gene amplification in breast cancer: a rogues’ gallery of challenging diagnostic cases: UKNEQAS interpretation guidelines and research recommendations. Am. J. Clin. Pathol. 137, 595–605 (2012).•• First paper that gives a practical approach for how to manage and to report challenging and equivocal HER2 FISH signals patterns.
  MedlineGoogle Scholar
• 84 Vance GH, Barry TS, Bloom KJ et al. Genetic heterogeneity in HER2 testing in breast cancer: panel summary and guidelines. Arch. Pathol. Lab. Med. 133, 611–612 (2009).
  MedlineGoogle Scholar
• 85 Bartlett JM, Ibrahim M, Jasani B et al. External quality assurance of HER2 fluorescence in situ hybridisation testing: results of a UK NEQAS pilot scheme. J. Clin. Pathol. 60, 816–819 (2007).• Points out the importance and results of external quality assurance scheme of HER2 FISH test in breast cancers.
  Medline CASGoogle Scholar
• 86 Martin V, Camponovo A, Ghisletta M et al. Internal quality assurance program for ERBB2 (HER2) testing improves the selection of breast cancer patients for treatment with trastuzumab. Patholog. Res. Int. 261857 (2012) (2012).
  Google Scholar
• 87 Hechtman JF, Polydorides AD. HER2/neu gene amplification and protein overexpression in gastric and gastroesophageal junction adenocarcinoma: a review of histopathology, diagnostic testing, and clinical implications. Arch. Pathol. Lab. Med. 136, 691–697 (2012).
  MedlineGoogle Scholar
• 88 Tanner M, Hollmén M, Junttila TT 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. 16, 273–278 (2005).
  Medline CASGoogle Scholar
• 89 Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann. Oncol. 19, 1523–1529 (2008).
  Medline CASGoogle Scholar
• 90 Cruz-Reyes C, Gamboa-Dominguez A. HER2 amplification in gastric cancer is a rare event restricted to the intestinal phenotype. Int. J. Surg. Pathol. 21, 240–246 (2013).
  Medline CASGoogle Scholar
• 91 Park DI, Yun JW, Park JH et al. HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig. Dis. Sci. 51, 1371–1379 (2006).
  Medline CASGoogle Scholar
• 92 Chen C, Yang JM, Hu TT et al. Prognostic role of human epidermal growth factor receptor in gastric cancer: a systematic review and meta-analysis. Arch. Med. Res. 44, 380–389 (2013).
  Medline CASGoogle Scholar
• 93 Hofmann M, Stoss O, Shi D et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 52, 797–805 (2008).• Reports in detail the specific system for HER2 interpretation in gastric cancer, proposed during the ToGA trial.
  Medline CASGoogle Scholar
• 94 Rüschoff J, Dietel M, Baretton G et al. HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Virchows Arch. 457, 299–307 (2010).•• Highlights recommendations and guidelines about how to evaluate HER2 immunohistochemistry test in gastric cancer.
  Medline CASGoogle Scholar
• 95 Lee S, de Boer WB, Fermoyle S et al. Human epidermal growth factor receptor 2 testing in gastric carcinoma: issues related to heterogeneity in biopsies and resections. Histopathology 59, 832–840 (2011).
  MedlineGoogle Scholar
• 96 Radu OM, Foxwell T, Cieply K et al. HER2 amplification in gastroesophageal adenocarcinoma: correlation of two antibodies using gastric cancer scoring criteria, H score, and digital image analysis with fluorescence in situ hybridization. Am. J. Clin. Pathol. 137, 583–594 (2012).
  MedlineGoogle Scholar
• 97 Ross JS, Mulcahy M. HER2 testing in gastric/gastroesophageal junction adenocarcinomas: unique features of a familiar test. Gastrointest. Cancer Res. 4, 62–66 (2011).
  MedlineGoogle Scholar
• 98 Tafe LJ, Janjigian YY, Zaidinski M et al. Human epidermal growth factor receptor 2 testing in gastroesophageal cancer: correlation between immunohistochemistry and fluorescence in situ hybridization. Arch. Pathol. Lab. Med. 135, 1460–1465 (2011).
  Medline CASGoogle Scholar
• 99 Herceptin: trastuzumab. www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000278/human_med_000818.jsp&mid=WC0b01ac058001d124
  Google Scholar
• 100 FDA approval for trastuzumab. www.cancer.gov/cancertopics/druginfo/fda-trastuzumab
  Google Scholar
• 101 Bartlett JM, Starczynski J, Atkey N et al. HER2 testing in the UK: recommendations for breast and gastric in-situ hybridisation methods. J. Clin. Pathol. 64, 649–653 (2011).
  Medline CASGoogle Scholar
• 102 Kim MA, Lee HJ, Yang HK et al. Heterogeneous amplification of ERBB2 in primary lesions is responsible for the discordant ERBB2 status of primary and metastatic lesions in gastric carcinoma. Histopathology 59, 822–831 (2011).
  MedlineGoogle Scholar
• 103 Marx AH, Tharun L, Muth J et al. HER-2 amplification is highly homogenous in gastric cancer. Hum. Pathol. 40, 769–777 (2009).
  Medline CASGoogle Scholar
• 104 Cho EY, Park K, Do I et al. Heterogeneity of ERBB2 in gastric carcinomas: a study of tissue microarray and matched primary and metastatic carcinomas. Mod. Pathol. 26, 677–684 (2013).
  Medline CASGoogle Scholar
• 105 Drebber U, Madeja M, Odenthal M et al. β-catenin and Her2/neu expression in rectal cancer: association with histomorphological response to neoadjuvant therapy and prognosis. Int. J. Colorectal Dis. 26, 1127–1134 (2011).
  MedlineGoogle Scholar
• 106 Kapitanović S, Radosević S, Kapitanović M et al. The expression of p185(HER-2/neu) correlates with the stage of disease and survival in colorectal cancer. Gastroenterology 112, 1103–1113 (1997).
  Medline CASGoogle Scholar
• 107 Martin V, Landi L, Molinari F et al. HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients. Br. J. Cancer 108, 668–675 (2013).•• Points out a dual role played by HER2 in colorectal cancer.
  Medline CASGoogle Scholar
• 108 Sameer AS. Colorectal cancer: molecular mutations and polymorphisms. Front. Oncol. 3, 114 (2013).
  MedlineGoogle Scholar
• 109 Li Q, Wang D, Li J et al. Clinicopathological and prognostic significance of HER-2/neu and VEGF expression in colon carcinomas. BMC Cancer 11, 277 (2011).
  MedlineGoogle Scholar
• 110 Lu Y, Jingyan G, Baorong S et al. Expression of EGFR, Her2 predict lymph node metastasis (LNM)-associated metastasis in colorectal cancer. Cancer Biomark. 11, 219–226 (2012).
  Medline CASGoogle Scholar
• 111 Bertotti A, Migliardi G, Galimi F et al. A molecularly annotated platform of patient-derived xenografts (‘xenopatients’) identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov. 1, 508–523 (2011).•• First paper showing efficacy of HER2-targeted therapies in colorectal cancer.
  Medline CASGoogle Scholar
• 112 Sorscher SM. Marked response to single agent trastuzumab in a patient with metastatic HER-2 gene amplified rectal cancer. Cancer Invest. 29, 456–459 (2011).
  Medline CASGoogle Scholar
• 113 Yonesaka K, Zejnullahu K, Okamoto I et al. Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Sci. Transl. Med. 3, 99ra86 (2011).
  Medline CASGoogle Scholar
• 114 Glisson B, Colevas AD, Haddad R et al. HER2 expression in salivary gland carcinomas: dependence on histological subtype. Clin. Cancer Res. 10, 944–946 (2004).
  Medline CASGoogle Scholar
• 115 Hillig T, Thode J, Breinholt MF et al. Assessing HER2 amplification by IHC, FISH, and real-time polymerase chain reaction analysis (real-time PCR) following LCM in formalin-fixed paraffin embedded tissue from 40 women with ovarian cancer. APMIS 120, 1000–1007 (2012).
  Medline CASGoogle Scholar
• 116 Giannoni C, El-Naggar AK, Ordonez NG et al. C-erbB-2/neu oncogene and Ki67 analysis in the assessment of palatal salivary gland neoplasms. Otolaryngol. Head Neck Surg. 112, 391–398 (1995).
  Medline CASGoogle Scholar
• 117 Shintani S, Funayama T, Yoshihama Y et al. Expression of C-erbB family gene products in adenoid cystic carcinoma of salivary glands: an immunohistochemical study. Anticancer Res. 15, 2623–2626 (1995).
  Medline CASGoogle Scholar
• 118 Khan AJ, Digiovanna MP, Ross DA et al. Adenoid cystic carcinoma: a retrospective clinical review. Int. J. Cancer. 96, 149–158 (2001).
  Medline CASGoogle Scholar
• 119 Press MF, Pike MC, Hung G et al. Amplification and overexpression of HER-2/neu in carcinomas of the salivary gland: correlation with poor prognosis. Cancer Res. 54, 5675–5682 (1994).
  Medline CASGoogle Scholar
• 120 Ching CB, Amin MB, Tubbs RR et al. HER2 gene amplification occurs frequently in the micropapillary variant of urothelial carcinoma: analysis by dual-color in situ hybridization. Mod. Pathol. 24, 1111–1119 (2011).
  Medline CASGoogle Scholar
• 121 Schneider SA, Sukov WR, Frank I et al. Outcome of patients with micropapillary urothelial carcinoma following radical cystectomy: ERBB2 (HER2) amplification identifies patients with poor outcome. Mod. Pathol. (2013) (In press).
  MedlineGoogle Scholar
• 122 Hirsch FR, Varella-Garcia M, McCoy J et al. Increased epidermal growth factor receptor gene copy number detected by fluorescence in situ hybridization associates with increased sensitivity to gefitinib in patients with bronchioloalveolar carcinoma subtypes: a Southwest Oncology Group Study. J. Clin. Oncol. 23, 6838–6845 (2005).
  Medline CASGoogle Scholar
• 123 Firwana B, Atassi B, Hasan R et al. Trastuzumab for Her2/neu-positive metastatic salivary gland carcinoma: case report and review of the literature. J. Med. 2, 71–73 (2012).
  Google Scholar
• 124 Kaidar-Person O, Billan S, Kuten A. Targeted therapy with trastuzumab for advanced salivary ductal carcinoma: case report and literature review. Med. Oncol. 29, 704–706 (2012).
  MedlineGoogle Scholar
• 125 Kadowaki S, Yatabe Y, Hirakawa H et al. Complete response to trastuzumab-based chemotherapy in a patient with human epidermal growth factor receptor-2-positive metastatic salivary duct carcinoma ex pleomorphic adenoma. Case Rep. Oncol. 6, 450–455 (2013).
  MedlineGoogle Scholar
• 126 Haddad RI, Colevas AD, Glisson B et al. Herceptin in patients with advanced or metastatic salivary gland carcinomas. A Phase II study. Oral Oncol. 39, 724–727 (2003).
  Medline CASGoogle Scholar
• 127 Simonetti S, Russo R, Ciancia G et al. Role of polysomy 17 in transitional cell carcinoma of the bladder: immunohistochemical study of HER2/neu expression and fish analysis of c-erbB-2 gene and chromosome 17. Int. J. Surg Pathol. 17, 198–205 (2009).
  MedlineGoogle Scholar
• 128 Inoue T, Sato K, Tsuchiya N et al. Numeric aberrations of HER2 and chromosome 17 detected by fluorescence in situ hybridization in urine-exfoliated cells from patients with urothelial carcinoma. Urology 64, 617–621 (2004).
  MedlineGoogle Scholar
• 129 Skagias L, Politi E, Karameris A et al. Prognostic impact of HER2/neu protein in urothelial bladder cancer. Survival analysis of 80 cases and an overview of almost 20 years’ research. J. BUON 14, 457–462 (2009).
  Medline CASGoogle Scholar
• 130 Hussain MH, MacVicar GR, Petrylak DP et al. Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter Phase II National Cancer Institute trial. J. Clin. Oncol. 25, 2218–2224 (2007).
  Medline CASGoogle Scholar
• 131 Peyromaure M, Scotté F, Amsellem-Ouazana D et al. Trastuzumab (Herceptin) in metastatic transitional cell carcinoma of the urinary tract: report on six patients. Eur. Urol. 48, 771–775 (2005).
  Medline CASGoogle Scholar
• 132 Salzberg M, Borner M, Bauer JA et al. Trastuzumab (Herceptin) in patients with HER-2-overexpressing metastatic or locally advanced transitional cell carcinoma of the bladder: report on 7 patients. Eur. J. Cancer 42, 2660–2661 (2006).
  Medline CASGoogle Scholar
• 133 Serrano-Olvera A, Duenas-Gonzalez A, Gallardo-Rincon D, Candelaria M, De la Garza-Salazar J. Prognostic, predictive and therapeutic implications of HER2 in invasive epithelial ovarian cancer. Cancer Treat. Rev. 32, 180–190 (2006).
  Medline CASGoogle Scholar
• 134 Hogdall EV, Christensen L, Kjaer SK et al. Distribution of HER-2 overexpression in ovarian carcinoma tissue and its prognostic value in patients with ovarian carcinoma: from the Danish MALOVA Ovarian Cancer Study. Cancer 98, 66–73 (2003).
  Medline CASGoogle Scholar
• 135 Lassus H, Leminen A, Vayrynen A et al. ERBB2 amplification is superior to protein expression status in predicting patient outcome in serous ovarian carcinoma. Gynecol. Oncol. 92, 31–39 (2004).
  Medline CASGoogle Scholar
• 136 Camilleri-Broët S, Hardy-Bessard AC, Le Tourneau A et al. HER-2 overexpression is an independent marker of poor prognosis of advanced primary ovarian carcinoma: a multicenter study of the GINECO group. Ann. Oncol. 15, 104–112 (2004).
  Medline CASGoogle Scholar
• 137 Verri E, Guglielmini P, Puntoni M et al. HER2/neu oncoprotein overexpression in epithelial ovarian cancer: evaluation of its prevalence and prognostic significance. Clinical study. Oncology 68, 154–161 (2005).
  Medline CASGoogle Scholar
• 138 Farley J, Fuchiuji S, Darcy KM et al. Associations between ERBB2 amplification and progression-free survival and overall survival in advanced stage, suboptimally-resected epithelial ovarian cancers: a Gynecologic Oncology Group Study. Gynecol. Oncol. 113, 341–347 (2009).
  Medline CASGoogle Scholar
• 139 Sheng Q, Liu J. The therapeutic potential of targeting the EGFR family in epithelial ovarian cancer. Br. J. Cancer 104, 1241–1245 (2011).
  Medline CASGoogle Scholar
• 140 Bookman MA, Darcy KM, Clarke-Pearson D, Boothby RA, Horowitz IR. Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a Phase II trial of the Gynecologic Oncology Group. J. Clin. Oncol. 21, 283–290 (2003).
  Medline CASGoogle Scholar
• 141 Tan D, Deeb G, Wang J et al. HER-2/neu protein expression and gene alteration in stage I–IIIA non-small-cell lung cancer: a study of 140 cases using a combination of high throughput tissue microarray, immunohistochemistry, and fluorescent in situ hybridization. Diagn. Mol. Pathol. 12, 201–211 (2003).
  Medline CASGoogle Scholar
• 142 Gatzemeier U, Groth G, Butts C et al. Randomized Phase II trial of gemcitabine-cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer. Ann. Oncol. 15, 19–27 (2004).
  Medline CASGoogle Scholar
• 143 Zinner RG, Glisson BS, Fossella FV et al. Trastuzumab in combination with cisplatin and gemcitabine in patients with Her2-overexpressing, untreated, advanced non-small cell lung cancer: report of a Phase II trial and findings regarding optimal identification of patients with Her2-overexpressing disease. Lung Cancer 44, 99–110 (2004).
  MedlineGoogle Scholar
• 144 Clamon G, Herndon J, Kern J et al. Lack of trastuzumab activity in nonsmall cell lung carcinoma with overexpression of erb-B2: 39810: a Phase II trial of cancer and leukemia group B. Cancer 103, 1670–1675 (2005).
  Medline CASGoogle Scholar
• 145 Mazières J, Peters S, Lepage B et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J. Clin. Oncol. 31, 1997–2003 (2013).
  Medline CASGoogle Scholar
• 146 Stephens P, Hunter C, Bignell G et al. Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature 431, 525–526 (2004).
  Medline CASGoogle Scholar
• 147 Herter-Sprie GS, Greulich H, Wong KK. Activating mutations in ERBB2 and their impact on diagnostics and treatment. Front. Oncol. 3, 86 (2013).
  MedlineGoogle Scholar