Mide Kanserlerinde HER2 Değerlendirmesi

İlerlemiş mide ve gastroözofageal bileşke karsinomlarında tedaviye Trastuzumab eklenmesi, Her2 pozitif tümörlü hastalarda sağkalım avantajı sağlamıştır. Bu tedaviden faydalanabilecek hastaların Her2 testi ile belirlenmesi gerekmektedir. Meme karsinomlarından sonra, mide karsinomlarında da Her2 testi patoloji laboratuarlarının günlük işleri arasına girmiştir. Mide karsinomlarında Her2 testi, meme karsinomlarındakine benzer özellikler içermekle birlikte, bilinmesi gereken farklı yönleri de vardır. Bu farklar, başlıca mide karsinomlarında Her2 pozitifliğinin daha heterojen olması ve karsinom hücre membranlarında, reseptörlerin bazolateral yerleşimlerinden kaynaklanmaktadır. Her2 testinde kullanılan immünhistokimyasal ve in situ hibridizasyon testleri, çoğu laboratuarda kullanılır testler arasında olmakla birlikte, skorlama kriterleri karışıktır ve doğru sonuç için deneyim gerektirmektedir. Bu testlerde doğruluğu sağlamak için analitik koşullar kadar preanalitik koşullar da etkilidir.

Anahtar Kelimeler:

Mide neoplazmları, HER2

HER2 Assessment in Gastric Carcinoma

Addition of Trastuzumab in management of advanced gastric and gastroesophageal carcinomas, has provided benefit in overall survival of those with Her2 positive tumors. For eligibility of patients for this therapy, Her2 test is done. Following breast carcinomas, Her2 testing in gastric carcinomas are also added to the routine work of pathology laboratories. Although Her2 test in gastric carcinomas has similar features with that of breast, it has some aspects to be known well. These aspects have arisen mainly because heterogenous Her2 positivity and basolateral settling of the receptors in gastric carcinoma cells. Although Her2 immunohistochemical and in situ hybridisation tests are among routine tests of most laboratories, scoring criteria are complex and need experience for accuracte results. In achieving accurate results in these tests, prenanalytical as well as the analytical conditions, are also effective.

Keywords:

Gastric neoplasms, HER2,

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Akiyama T, Sudo C, Ogawara H, et al. The product of the human c-erbB–2 gene: a 185-kilo-Dalton glycoprotein with tyrosine kinase activity. Science 1986;232:1644-6
Coussens L, Yang-Feng TL, Liao YC, et al. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 1985;230:1132-9
King CR, Kraus MH, Aaronson SA. Amplification of a novel v-erbB2 related gene in human mammary carcinoma. Science 1985;229:974-6
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 1987;235:177-82
Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu protooncogene in human breast and ovarian cancer. Science 1989;244:707-12
Fukushige S, Matsubara K, Yoshida M, et al. Localization of a novel verbB-related gene, c-erbB-2, on human chromosome 17 and its amplification in a gastric cancer cell line. Mol Cell Biol 1986;6:955-8
Bang YJ, Cutsem EV, 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 2010;376:687-97
Konecny G, Pauletti G, Pegram M, et al. Quantitative association between HER-2 ⁄ neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. J Natl Cancer Inst 2003;95:142-53
Owens MA, Horten BC, Da Silva MM. HER2 amplification hybridization immunohistochemistry in a cohort of 6556 breast cancer tissues. Clin Breast Cancer 2004;5:63-9
Penault-Llorca F, Vincent-Salomon A, Mathieu MC, et al. Incidence and implications of HER2 and hormonal diagnosed metastatic breast cancer (MBC). J Clin Oncol (Meeting Abstracts) 2005;23;69s (Abstract 764) in newly
Giuffrè G, Ieni A, Barresi V, Caruso RA, Tuccari G. HER2 status in unusual histological variants of gastric adenocarcinomas. J Clin Pathol 2012;65:237- 41
Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 2008;52:797-805
Jorgensen JT. Targeted HER2 treatment in advanced gastric cancer. Oncology 2010;78:26-33
Kim JW, Im SA, Kim M, et al. The prognostic significance of HER2 positivity for advanced gastric cancer patients undergoing first-line modified FOLFOX-6 regimen. Anticancer Res 2012;32:1547- 53
Kim MA, Jung EJ, Lee HS, et al. Evaluation of HER- 2 gene immunohistochemistry, hybridization, and real-time quantitative polymerase chain reaction. Hum Pathol 2007;38:1386-93 using situ fluorescence in
Lee S, 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 2011;59:832-40
Tanner M, Hollme´n M, Junttila TT, et al. Amplification of HER-2 in gastric carcinoma: association amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol 2005;16:273-8
Kunz PL, Mojtahed A, Fisher GA, et al. Her2 expression in gastric and gastroesophageal junction adenocarcinoma clinicopathologic analysis with proposed approach to Her2 assessment. Appl Immunohistochem Mol Morphol 2012;20:13-24 a US population:
Davison JM, Pai RK. Her2 assessment in upper gastrointestinal tract adenocarcinoma. A practical, algorithmic approach. Surg Pathol Clin 2013;6:391
Carter P, Presta L, Gorman CM, et al. Humanization of an antip185HER2 antibody for human cancer therapy. Proc Natl Acad Sci USA. 1992;89:4285-9
Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999;17:2639-48
Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005;353:1659-72
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- 84
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;344:783-92
Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first- line treatment of HER2- overexpressing metastatic breast cancer. J Clin Oncol 2002;20:719-26
Mello RA, Marques AM, Araujo A. HER2 therapies and gastric cancer: a step forward. World J Gastroenterol 2013;19:6165
Rüschoff J, Dietel M, Baretton G, et al. HER2 diagnostics in gastric cancer—guideline validation and immunohistochemical 2010;457:299-307 of standardized testing. Virchows Arch
Kushima R, Kuwata T, Yao T, et al. Interpretation of HER2 tests in gastric cancer: confirmation of interobserver differences and validation of a QA/QC educational program. Virchows Arch 2014;464:539- 45
Lee AH, Key HP, Bell JA, et al. Concordance of Her2 status assessed on needle core biopsy and surgical specimens of invasive carcinoma of the breast. Histopathology 2012;60:880-4
Grabsch H, Sivakumar S, Gray S, et al. Her2 expression in gastric cancer: rare, heterogenous and of no prognostic value-cocnclusions from 924 cases of two independant series. Cell Oncol 2010;32:57-65
Dang HZ, Yu Y, Jiao SC. Prognosis of HER2 over- expressing gastric cancer patients with liver metastasis. World J Gastroenterol 2012;18:2402-7
Jorgensen JT, Hersom M. HER2 as a Prognostic Marker in Gastric Cancer-A Systematic Analysis of Data from the Literature. J Cancer 2012;3:137-44
Park DI, Yun JW, Park JH, et al. HER2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci 2006;51:1371-9
Gomez-Martin C, Garralda E, Echarri MJ, et al. HER2/neu testing for anti-HER2-based therapies in patients with unresectable and/or metastatic gastric cancer. J Clin Pathol 2012;65:751-7
Janjigian YY, Werner D, Pauligk C, et al. Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis. Ann Oncol 2012;10:2656-62
Rüschoff J, Hanna W, Bilous M, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol 2012;25:637-50
Moehler M, Al-Batran SE, Andus T, et al. German S3 esophagogastric 2011;49:461-531 Gastroenterology
Kosa C, Kardos L, Kovacs J, Szollosi Z. Comparison of dual-color dual-hapten brightfield in situ hybridization (DDISH) and fluorescence in situ hybridization in breast cancer HER2 assessment. Pathol Res Pract 2013;209:147-50
García-García E, Gómez-Martín C, Angulo B, et al. Hybridization for human epidermal growth factor receptor 2 testing in gastric carcinoma: a comparison of fluorescence in-situ hybridization with a novel fully hybridization method. Hybridization for human epidermal growth factor receptor 2 testing in gastric carcinoma: a comparison of fluorescence in-situ hybridization with a novel fully automated dual- colour Histopathology 2011;59:8-17 hybridization method.
Hanna WM, Rüschoff J, Bilous M, et al. HER2 in situ implications heterogeneity. Mod Pathol 2014;27:4-18 17 and genetic of polysomy
Seidman AD, Berry D, Cirrincione C, et al. Randomized Phase III Trial of Weekly Compared With Every-3-Weeks Paclitaxel for Metastatic Breast Cancer, Overexpressors Trastuzumab or Not in HER-2 Nonoverexpressors: Final Results of Cancer and leukemia Group B Protocol 9840. J Clin Oncol 2008;10:1642 HER-2 Random to
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 2013;31:3997-4013
Wolff AC, Hammond 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. Arch Pathol Lab Med 2007;131:18-43
Bozzetti C, Negri FV, Lagrasta CA, et al. Comparison of Her2 status in primary and paired metastatic sites of gastric carcinoma. Br J Cancer 2011;104:1372-6
Kim MA, Lee HJ, Yang HK, et al. Heterogenous amplification of ERBB2 in primary lesions is responsible for the discordant ERBB’ status of primary and metastatic lesions in gastric carcinoma. Histopathology 2011;59:822-31
Negri FV, Bozzetti C, Ardizzoni A, et al. Her2 discordance between primary gastric carcinoma and paired lymph node metastasis. Hum Pathol 2011;42:909-10 (author reply)
Perrone G, Amato M, Callea M, et al. Her2 amplification status in gastric and gastroesophageal junctioncancer in routine clinical practice: which sample should be used? Histopathology 2012;61:134- 5