HER2 expression status in diverse cancers: review of results from 37,992 patients
Tóm tắt
Human epidermal growth factor receptor 2 (HER2) amplification/overexpression is an effective therapeutic target in breast and gastric cancer. Although HER2 positivity has been reported in other malignancies, previous studies generally focused on one cancer type, making it challenging to compare HER2 positivity across studies/malignancies. Herein, we examined 37,992 patient samples for HER2 expression (+/− amplification) in a single laboratory. All 37,992 patients were tested by immunohistochemistry (IHC); 21,642 of them were also examined for HER2 amplification with either fluorescent in situ hybridization (FISH) (11,670 patients) or chromogenic in situ hybridization (CISH) (9,972 patients); 18,262 patients had tumors other than breast or gastric cancer. All tissues were analyzed in a Clinical Laboratory Improvement Amendments (CLIA) laboratory (Caris Life Sciences) at the request of referring physicians. HER2 protein overexpression was found in 2.7 % of samples. Over-expressed HER2 was detected predominantly in malignancies of epithelial origin; for cancers derived from mesenchyme, neuroendocrine tissue, central nervous system, and kidney, HER2 expression and amplification were remarkably rare or non-existent. Bladder carcinomas, gallbladder, extrahepatic cholangiocarcinomas, cervical, uterine, and testicular cancers showed HER2 positivity rates of 12.4, 9.8, 6.3, 3.9, 3.0, and 2.4 %, respectively. HER2 overexpression and/or amplification is frequently found across tumor types. These observations may have significant therapeutic implications in cancers not traditionally thought to benefit from anti-HER2 therapies.
Tài liệu tham khảo
Garrett, T. P. J., McKern, N. M., Lou, M., Elleman, T. C., Adams, T. E., Lovrecz, G. O., … Ward, C. W. (2003). The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors. Molecular Cell, 11(2), 495–505.
Graus-Porta, D., Beerli, R. R., Daly, J. M., & Hynes, N. E. (1997). ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. The EMBO Journal, 16(7), 1647–1655. doi:10.1093/emboj/16.7.1647.
Holbro, T., Beerli, R. R., Maurer, F., Koziczak, M., Barbas, C. F., 3rd, & Hynes, N. E. (2003). The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proceedings of the National Academy of Sciences of the United States of America, 100(15), 8933–8938. doi:10.1073/pnas.1537685100.
Di Fiore, P. P., Pierce, J. H., Kraus, M. H., Segatto, O., King, C. R., & Aaronson, S. A. (1987). erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science (New York, N.Y.), 237(4811), 178–182.
Ursini-Siegel, J., Schade, B., Cardiff, R. D., & Muller, W. J. (2007). Insights from transgenic mouse models of ERBB2-induced breast cancer. Nature reviews. Cancer, 7(5), 389–397. doi:10.1038/nrc2127.
Bang, Y.-J., Van Cutsem, E., Feyereislova, A., Chung, H. C., Shen, L., Sawaki, A., … ToGA Trial Investigators. (2010). 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(9742), 687–697. doi:10.1016/S0140-6736(10)61121-X.
Romond, E. H., Perez, E. A., Bryant, J., Suman, V. J., Geyer, C. E., Jr, Davidson, N. E., … Wolmark, N. (2005). Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. The New England Journal of Medicine, 353(16), 1673–1684. doi:10.1056/NEJMoa052122.
CDER. (n.d.). Retrieved from http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm230418.htm
Baselga, J., Cortés, J., Kim, S.-B., Im, S.-A., Hegg, R., Im, Y.-H., … Swain, S. M. (2012). Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer. New England Journal of Medicine, 366(2), 109–119. doi:10.1056/NEJMoa1113216.
Verma, S., Miles, D., Gianni, L., Krop, I. E., Welslau, M., Baselga, J., … EMILIA Study Group. (2012). Trastuzumab emtansine for HER2-positive advanced breast cancer. The New England Journal of Medicine, 367(19), 1783–1791. doi:10.1056/NEJMoa1209124.
Nardi, V., Sadow, P. M., Juric, D., Zhao, D., Cosper, A. K., Bergethon, K., … Dias-Santagata, D. (2013). Detection of novel actionable genetic changes in salivary duct carcinoma helps direct patient treatment. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 19(2), 480–490. doi:10.1158/1078-0432.CCR-12-1842
Williams, M. D., Roberts, D. B., Kies, M. S., Mao, L., Weber, R. S., & El-Naggar, A. K. (2010). Genetic and expression analysis of HER-2 and EGFR genes in salivary duct carcinoma: empirical and therapeutic significance. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 16(8), 2266–2274. doi:10.1158/1078-0432.CCR-09-0238.
Yan, M., Parker, B. A., Schwab, R., & Kurzrock, R. (n.d.). HER2 aberrations in cancer: Implications for therapy. Cancer Treatment Reviews. doi:10.1016/j.ctrv.2014.02.008
Wolff, A. C., Hammond, M. E. H., Schwartz, J. N., Hagerty, K. L., Allred, D. C., Cote, R. J., … College of American Pathologists. (2007). American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 25(1), 118–145. doi:10.1200/JCO.2006.09.2775
Falchook, G. S., Janku, F., Tsao, A. S., Bastida, C. C., Stewart, D. J., & Kurzrock, R. (2013). Non-small-cell lung cancer with HER2 exon 20 mutation: regression with dual HER2 inhibition and anti-VEGF combination treatment. Journal of Thoracic Oncology: official Publication of the International Association for the Study of Lung Cancer, 8(2), e19–e20. doi:10.1097/JTO.0b013e31827ce38e.
Falchook, G. S., Lippman, S. M., Bastida, C. C., & Kurzrock, R. (2014). Human epidermal receptor 2-amplified salivary duct carcinoma: regression with dual human epidermal receptor 2 inhibition and anti-vascular endothelial growth factor combination treatment. Head & Neck, 36(3), E25–E27. doi:10.1002/hed.23429.
Cappuzzo, F., Bemis, L., & Varella-Garcia, M. (2006). HER2 mutation and response to trastuzumab therapy in non-small-cell lung cancer. The New England Journal of Medicine, 354(24), 2619–2621. doi:10.1056/NEJMc060020.
Kelly, R. J., Carter, C. A., & Giaccone, G. (2012). HER2 mutations in non-small-cell lung cancer can be continually targeted. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 30(26), 3318–3319. doi:10.1200/JCO.2012.43.4902.
Wolff, A. C., Hammond, M. E. H., Hicks, D. G., Dowsett, M., McShane, L. M., Allison, K. H., … College of American Pathologists. (2013). 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. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 31(31), 3997–4013. doi:10.1200/JCO.2013.50.9984.
Ruschoff, J., Dietel, M., Baretton, G., Arbogast, S., Walch, A., Monges, G., … Kreipe, H. H. (2010). HER2 diagnostics in gastric cancer--guideline validation and development of standardized immunohistochemical testing. Virchows Archiv, 457(3), 299–307. doi:10.1007/s00428-010-0952-2.
Charfi, S., Khabir, A., Mnif, H., Ellouze, S., Mhiri, M. N., & Boudawara-Sellami, T. (2013). Immunohistochemical expression of HER2 in urothelial bladder carcinoma and its correlation with p53 and p63 expression. Journal of Microscopy and Ultrastructure, 1(1–2), 17–21. doi:10.1016/j.jmau.2013.06.001.
Fleischmann, A., Rotzer, D., Seiler, R., Studer, U. E., & Thalmann, G. N. (2011). Her2 amplification is significantly more frequent in lymph node metastases from urothelial bladder cancer than in the primary tumours. European Urology, 60(2), 350–357. doi:10.1016/j.eururo.2011.05.035.
Laé, M., Couturier, J., Oudard, S., Radvanyi, F., Beuzeboc, P., & Vieillefond, A. (2010). Assessing HER2 gene amplification as a potential target for therapy in invasive urothelial bladder cancer with a standardized methodology: results in 1005 patients. Annals of Oncology: Official Journal of the European Society for Medical Oncology / ESMO, 21(4), 815–819. doi:10.1093/annonc/mdp488.
Caner, V., Turk, N. S., Duzcan, F., Tufan, N. L. S., Kelten, E. C., Zencir, S., … Duzcan, S. E. (2008). No strong association between HER-2/neu protein overexpression and gene amplification in high-grade invasive urothelial carcinomas. Pathology oncology research: POR, 14(3), 261–266. doi:10.1007/s12253-008-9027-y.
Gandour-Edwards, R., Lara, P. N., Folkins, A. K., LaSalle, J. M., Beckett, L., Li, Y., … DeVere-White, R. (2002). Does HER2/neu expression provide prognostic information in patients with advanced urothelial carcinoma? Cancer, 95(5), 1009–1015. doi:10.1002/cncr.10808.
Varga, Z., Noske, A., Ramach, C., Padberg, B., & Moch, H. (2013). Assessment of HER2 status in breast cancer: overall positivity rate and accuracy by fluorescence in situ hybridization and immunohistochemistry in a single institution over 12 years: a quality control study. BMC Cancer, 13(1), 615. doi:10.1186/1471-2407-13-615.
Stenehjem, D. D., Yoo, M., Unni, S. K., Singhal, M., Bauer, H., Saverno, K., … Brixner, D. I. (2014). Assessment of HER2 testing patterns, HER2+ disease, and the utilization of HER2-directed therapy in early breast cancer. Breast Cancer (Dove Medical Press), 6, 169–177. doi:10.2147/BCTT.S69416
Chavez-Blanco, A., Perez-Sanchez, V., Gonzalez-Fierro, A., Vela-Chavez, T., Candelaria, M., Cetina, L., … Dueñas-Gonzalez, A. (2004). HER2 expression in cervical cancer as a potential therapeutic target. BMC Cancer, 4(1), 59. doi:10.1186/1471-2407-4-59.
Yoshikawa, D., Ojima, H., Iwasaki, M., Hiraoka, N., Kosuge, T., Kasai, S., … Shibata, T. (2008). Clinicopathological and prognostic significance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma. British Journal of Cancer, 98(2), 418–425. doi:10.1038/sj.bjc.6604129
Seo, A. N., Kwak, Y., Kim, D.-W., Kang, S.-B., Choe, G., Kim, W. H., & Lee, H. S. (2014). HER2 status in colorectal cancer: its clinical significance and the relationship between HER2 gene amplification and expression. PloS One, 9(5), e98528. doi:10.1371/journal.pone.0098528.
Schuell, B., Gruenberger, T., Scheithauer, W., Zielinski, C., & Wrba, F. (2006). HER 2/neu protein expression in colorectal cancer. BMC Cancer, 6(1), 123. doi:10.1186/1471-2407-6-123.
Ingold Heppner, B., Behrens, H.-M., Balschun, K., Haag, J., Krüger, S., Becker, T., & Röcken, C. (2014). HER2/neu testing in primary colorectal carcinoma. British Journal of Cancer, 111(10), 1977–1984. doi:10.1038/bjc.2014.483.
Yoon, H. H., Shi, Q., Sukov, W. R., Sattler, C. A., Wiktor, A. E., Wu, T.-T., … Sinicrope, F. A. (2013). HER2 testing in esophageal adenocarcinoma (EAC) using parallel tissue-based methods. Journal of Clinical Oncology, 31(suppl 4; abstr 2). Retrieved from http://meetinglibrary.asco.org/content/105406-133
Wang, T., Hsieh, E. T., Henry, P., Hanna, W., Streutker, C. J., & Grin, A. (2014). Matched biopsy and resection specimens of gastric and gastroesophageal adenocarcinoma show high concordance in HER2 status. Human Pathology, 45(5), 970–975. doi:10.1016/j.humpath.2013.12.010.
König, A. M., Reeh, M., Dancau, A.-M., Rathjens, M., Gros, S., Uzunoglu, F. G., … Izbicki, J. R. (2013). Concordance of HER2 status in primary tumour and lymph node metastases in patients with esophageal carcinoma. Anticancer Research, 33(11), 4975–4982.
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. Gastrointestinal Cancer Research : GCR, 7(2), 42–48.
Rüschoff, J., Hanna, W., Bilous, M., Hofmann, M., Osamura, R. Y., Penault-Llorca, F., … Viale, G. (2012). HER2 testing in gastric cancer: a practical approach. Modern Pathology, 25(5), 637–650. doi:10.1038/modpathol.2011.198.
Hofmann, M., Stoss, O., Shi, D., Büttner, R., Van De Vijver, M., Kim, W., … 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.
Sauter, G., Lee, J., Bartlett, J. M. S., Slamon, D. J., & Press, M. F. (2009). Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 27(8), 1323–1333. doi:10.1200/JCO.2007.14.8197.
Perez, E. A., Cortés, J., Gonzalez-Angulo, A. M., & Bartlett, J. M. S. (2014). HER2 testing: current status and future directions. Cancer Treatment Reviews, 40(2), 276–284. doi:10.1016/j.ctrv.2013.09.001.
Gown, A. M., Goldstein, L. C., Barry, T. S., Kussick, S. J., Kandalaft, P. L., Kim, P. M., & Tse, C. C. (2008). High concordance between immunohistochemistry and fluorescence in situ hybridization testing for HER2 status in breast cancer requires a normalized IHC scoring system. Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc, 21(10), 1271–1277. doi:10.1038/modpathol.2008.83.
Perez, E. A., Press, M. F., Dueck, A. C., Jenkins, R. B., Kim, C., Chen, B., … Slamon, D. J. (2013). Immunohistochemistry and fluorescence in situ hybridization assessment of HER2 in clinical trials of adjuvant therapy for breast cancer (NCCTG N9831, BCIRG 006, and BCIRG 005). Breast Cancer Research and Treatment, 138(1), 99–108. doi:10.1007/s10549-013-2444-y.
Bahreini, F., Soltanian, A. R., & Mehdipour, P. (2014). A meta-analysis on concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) to detect HER2 gene overexpression in breast cancer. Breast cancer (Tokyo, Japan). doi:10.1007/s12282-014-0528-0.
Chmielecki, J., Ross, J. S., Wang, K., Frampton, G. M., Palmer, G. A., Ali, S. M., … Stephens, P. J. (2015). Oncogenic Alterations in ERBB2/HER2 Represent Potential Therapeutic Targets Across Tumors From Diverse Anatomic Sites of Origin. The Oncologist, 20(1), 7–12. doi:10.1634/theoncologist.2014-0234
Galsky, M. D., Von Hoff, D. D., Neubauer, M., Anderson, T., Fleming, M., Nagarwala, Y., … Zaks, T. Z. (2012). Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors. Investigational New Drugs, 30(2), 695–701. doi:10.1007/s10637-010-9541-0.
Tsimberidou, A.-M., Iskander, N. G., Hong, D. S., Wheler, J. J., Falchook, G. S., Fu, S., … Kurzrock, R. (2012). Personalized medicine in a phase I clinical trials program: the MD Anderson Cancer Center initiative. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 18(22), 6373–6383. doi:10.1158/1078-0432.CCR-12-1627.
Heinrich, M. C., Joensuu, H., Demetri, G. D., Corless, C. L., Apperley, J., Fletcher, J. A., … Imatinib Target Exploration Consortium Study B2225. (2008). Phase II, open-label study evaluating the activity of imatinib in treating life-threatening malignancies known to be associated with imatinib-sensitive tyrosine kinases. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 14(9), 2717–2725. doi:10.1158/1078-0432.CCR-07-4575.
Janku, F., Hong, D. S., Fu, S., Piha-Paul, S. A., Naing, A., Falchook, G. S., … Kurzrock, R. (2014). Assessing PIK3CA and PTEN in early-phase trials with PI3K/AKT/mTOR inhibitors. Cell Reports, 6(2), 377–387. doi:10.1016/j.celrep.2013.12.035