بررسی نتایج به دست آمده با تکنیک Immunohistochemistry (IHC) در ارزیابی افزایش بیان HER2 در بافت کارسینومای مهاجم مجرایی پستان با روش Fluorescence in situ hybridization (FISH)

نوع مقاله : مقاله های پژوهشی

نویسندگان

1 استاد، گروه پاتولوژی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

2 دانشجوی پزشکی، دانشکده‌ی پزشکی و کمیته‌ی تحقیقات دانشجویی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

3 دانشجوی پزشکی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی بوشهر، بوشهر، ایران

4 متخصص پاتولوژی، اصفهان، ایران

5 کارشناس ارشد، گروه اپیدمیولوژی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

چکیده

مقدمه: کارسینومای پستان، شایع‌ترین سرطان در میان زنان است. ژن HER2 (2-Human epidermal growth factor receptor) یک پروتو انکوژن است که گیرنده‌ی تیروزین کیناز خانواده‌ی Epidermal growth factor receptor را کد می‌کند و افزایش بیان آن، در برخی موارد کارسینومای پستان دیده می‌شود. مطالعه‌ی حاضر، با هدف ارزیابی تکنیک Immunohistochemistry (IHC) در شناسایی موارد مثبت پروتئین HER2 به روش Fluorescence in situ hybridization (FISH) و بررسی ارتباط متغیرهای آسیب‌شناختی بالینی با بیان ژن HER2 انجام شد.روش‌ها: طی یک مطالعه‌ی مقطعی در سال 1393، 190 نمونه از بیماران مبتلا به کارسینومای مهاجم مجرایی که نتایج IHC آن‌ها از نظر HER2 به صورت ++ یا +++ گزارش شده بود، جمع‌آوری و به روش FISH، میزان بیان HER2 بررسی شد. همچنین، ارتباط بین عوامل آسیب‌شناختی بالینی شامل سن، درجه‌ی تومور و وضعیت هورمون گیرنده با بیان ژن HER2 ارزیابی شد. داده‌های به دست آمده با استفاده از نرم‌افزار SPSS تجزیه و تحلیل گردید.یافته‌ها: از 190 نمونه‌ی مربوط به کارسینومای مهاجم پستان، از نظر HER2 در روش IHC، 160 نمونه ++ و 30 نمونه +++ بود. گیرنده‌ی استروژن (ER یا Estrogen receptor) در 2/64 درصد بیماران و گیرنده‌ی پروژسترون (PR یا Progesterone receptor) در 2/74 درصد آنان بیان شده بود. بلوک‌های مثبت روش FISH، از نظر HER2 در روش IHC، در 5/27 درصد ++ و 3/83 درصد +++ بود. موارد منفی گیرنده‌ی استروژن در بیماران HER2 مثبت، به طور معنی‌داری بیشتر بود (001/0 > P). بیماران HER2 مثبت از نظر گیرنده‌ی پروژسترون نیز بیشتر منفی بودند (013/0 = P).نتیجه‌گیری: در این مطالعه نشان داده شد که روش IHC به تنهایی روش مناسبی برای ارزیابی بیان HER2 و تصمیم‌گیری جهت درمان با Trastuzumab حتی در موارد IHC برابر +++ نیست.

کلیدواژه‌ها

عنوان مقاله [English]

Evaluation of Immunohistochemistry Technique in Detecting HER2 Overexpression in Invasive Ductal Breast Carcinoma Using Fluorescence in-situ Hybridization Method

نویسندگان [English]

  • Azar Baradaran 1
  • Parvaneh Hajalikhani 2
  • Mohammad Kazem Gheybi 3
  • Mohammad Reza Mohajeri 4
  • Ali Mehrabi-Koushki 5
1 Professor, Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2 Student of Medicine, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
3 Student of Medicine, School of Medicine, Boushehr University of Medical Sciences, Boushehr, Iran
4 Pathologist, Isfahan, Iran
5 Department of Epidemiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
چکیده [English]

Background: Breast cancer is the most common cancer among women. HER2 gene is a proto-oncogene that encodes the receptor of tyrosine kinase from epidermal growth factor receptor (EFGR) family. It is an important prognostic factor with a determinant role in treatment of breast cancer. There is no globally accepted method for determining the status of this gene and the method of choice is still a matter of debate. We aimed to evaluate the validity of immunohistochemistry (IHC) method in predicting HER2 status using fluorescence in-situ hybridization (FISH) method and also, to investigate some clinicopathological variables associated with HER2 amplification.Methods: In this cross-sectional study, 190 formalin-fixed and paraffin-embedded tissue specimens of invasive breast carcinoma with HER2 of ++ and +++ in IHC evaluation were enrolled. FISH method was performed on all these samples and the relationship of HER2 status and clinicopathological variables was evaluated.Findings: The studied population included 160 specimens of ++ and 30 specimens of +++ HER2 in IHC evaluation. The estrogen and progesterone receptors (ER and PR) were expressed in 64.2% and 74.2% of the specimens, respectively. HER2 amplification on FISH method was found in 27.5% and 83.3% of specimens of ++ and +++ HER2 in IHC evaluation, respectively. Tumors with HER2 amplification were more likely to be negative for estrogen (52.2% vs. 26.4%, P < 0.001) and progesterone (39.1% vs. 18.2 %, P = 0.013) receptors.Conclusion: This study showed that immunohistochemistry is not a good method for evaluating HER2 status and decision making about trastuzumab therapy even in patients with +++ HER2.

کلیدواژه‌ها [English]

  • Invasive breast carcinoma
  • Human epidermal growth factor receptor-2 (HER2)
  • Immunohistochemistry (IHC)
  • Fluorescent in situ hybridization (FISH)

مراجع

  1. Kumar V, Abbas AK, Fausto N, Aster J. Robbins and Cotran pathologic basis of disease. 8th ed. Philadelphia, PA: Saunders; 2010. p. 1089-90.
  2. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature 2000; 406(6797): 747-52.
  3. Mohammadi Torbati P, Fard Esfehani P. Androgen Receptor Analysis in Relation to Estrogen and Progesterone Receptors as well as Histological Grade for Ductal Carcinoma In Situ of the Breast. Iran J Pathol 2006; 1(4): 149-54.
  4. Lopez-Guerrero JA, Lombart-Cussac A, Noguera R, Navarro S, Pellin A, Almenar S, et al. HER2 amplification in recurrent breast cancer following breast-conserving therapy correlates with distant metastasis and poor survival. Int J Cancer 2006; 118(7): 1743-9.
  5. Moelans CB, de Weger RA, Van der Wall E, van Diest PJ. Current technologies for HER2 testing in breast cancer. Crit Rev Oncol Hematol 2011; 80(3): 380-92.
  6. Owens MA, Horten BC, Da Silva MM. HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues. Clin Breast Cancer 2004; 5(1): 63-9.
  7. Ithimakin S, Day KC, Malik F, Zen Q, Dawsey SJ, Bersano-Begey TF, et al. HER2 drives luminal breast cancer stem cells in the absence of HER2 amplification: implications for efficacy of adjuvant trastuzumab. Cancer Res 2013; 73(5): 1635-46.
  8. Ravdin PM, Chamness GC. The c-erbB-2 proto-oncogene as a prognostic and predictive marker in breast cancer: a paradigm for the development of other macromolecular markers--a review. Gene 1995; 159(1): 19-27.
  9. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, 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(3): 719-26.
  10. Reis-Filho JS, Pusztai L. Gene expression profiling in breast cancer: classification, prognostication, and prediction. Lancet 2011; 378(9805): 1812-23.
  11. Ji Y, Sheng L, Du X, Qiu G, Chen B, Wang X. Clinicopathological variables predicting HER-2 gene status in immunohistochemistry-equivocal (2+) invasive breast cancer. J Thorac Dis 2014; 6(7): 896-904.
  12. Mutlu H, Karaca H, Akca Z, Torun YA. Should fish test be performed to all patients with breast cancer? Med Sci (Turkey) 2013; 2(2): 539-47.
  13. Reddy JC, Reimann JD, Anderson SM, Klein PM. Concordance between central and local laboratory HER2 testing from a community-based clinical study. Clin Breast Cancer 2006; 7(2): 153-7.
  14. Saez A, Andreu FJ, Segui MA, Bare ML, Fernandez S, Dinares C, et al. HER-2 gene amplification by chromogenic in situ hybridisation (CISH) compared with fluorescence in situ hybridisation (FISH) in breast cancer-A study of two hundred cases. Breast 2006; 15(4): 519-27.
  15. Cuadros M, Villegas R. Systematic review of HER2 breast cancer testing. Appl Immunohistochem Mol Morphol 2009; 17(1): 1-7.
  16. Yoon N, Do IG, Cho EY. Analysis of HER2 status in breast carcinoma by fully automated HER2 fluorescence in situ hybridization (FISH): comparison of two immunohistochemical tests and manual FISH. APMIS 2014; 122(9): 755-60.
  17. Rosa FE, Silveira SM, Silveira CG, Bergamo NA, Neto FA, Domingues MA, et al. Quantitative real-time RT-PCR and chromogenic in situ hybridization: precise methods to detect HER-2 status in breast carcinoma. BMC Cancer 2009; 9: 90.
  18. Blackwell KL, Burstein HJ, Storniolo AM, Rugo H, Sledge G, Koehler M, 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 2010; 28(7): 1124-30.
  19. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, 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(1): 18-43.
  20. Pazhoomand R, Keyhani E, Banan M, Najmabadi H, Khodadadi F, Iraniparast A, et al. Detection of HER2 status in breast cancer: comparison of current methods with MLPA and real-time RT-PCR. Asian Pac J Cancer Prev 2013; 14(12): 7621-8.
  21. Dietel M, Ellis IO, Hofler H, Kreipe H, Moch H, Dankof A, et al. Comparison of automated silver enhanced in situ hybridisation (SISH) and fluorescence ISH (FISH) for the validation of HER2 gene status in breast carcinoma according to the guidelines of the American Society of Clinical Oncology and the College of American Pathologists. Virchows Arch 2007; 451(1): 19-25.
  22. Vanden B, I, Vanhentenrijk V, Drijkoningen M, Wlodarska I, Vandenberghe P, De Wolf-Peeters C. Real-time reverse transcription-PCR and fluorescence in-situ hybridization are complementary to understand the mechanisms involved in HER-2/neu overexpression in human breast carcinomas. Histopathology 2005; 46(4): 431-41.
  23. Press MF, Sauter G, Bernstein L, Villalobos IE, Mirlacher M, Zhou JY, et al. Diagnostic evaluation of HER-2 as a molecular target: an assessment of accuracy and reproducibility of laboratory testing in large, prospective, randomized clinical trials. Clin Cancer Res 2005; 11(18): 6598-607.
  24. Carlsson J, Nordgren H, Sjostrom J, Wester K, Villman K, Bengtsson NO, et al. HER2 expression in breast cancer primary tumours and corresponding metastases. Original data and literature review. Br J Cancer 2004; 90(12): 2344-8.
  25. Lee AH, Key HP, Bell JA, Hodi Z, Ellis IO. Breast carcinomas with borderline (2+) HER2 immunohistochemistry: percentage of cells with complete membrane staining for HER2 and the frequency of HER2 amplification. J Clin Pathol 2011; 64(6): 490-2.
  26. Chibon F, de M, I, Sierankowski G, Brouste V, Bonnefoi H, Debled M, et al. Prediction of HER2 gene status in Her2 2+ invasive breast cancer: a study of 108 cases comparing ASCO/CAP and FDA recommendations. Mod Pathol 2009; 22(3): 403-9.
  27. Dieci MV, Barbieri E, Bettelli S, Piacentini F, Omarini C, Ficarra G, et al. Predictors of human epidermal growth factor receptor 2 fluorescence in-situ hybridisation amplification in immunohistochemistry score 2+ infiltrating breast cancer: a single institution analysis. J Clin Pathol 2012; 65(6): 503-6.
  28. Liu C, Zhang H, Shuang C, Lu Y, Jin F, Xu H, et al. Alterations of ER, PR, HER-2/neu, and P53 protein expression in ductal breast carcinomas and clinical implications. Med Oncol 2010; 27(3): 747-52.
  29. Hanley K, Wang J, Bourne P, Yang Q, Gao AC, Lyman G, et al. Lack of expression of androgen receptor may play a critical role in transformation from in situ to invasive basal subtype of high-grade ductal carcinoma of the breast. Hum Pathol 2008; 39(3): 386-92.
  30. Bahreini F, Soltanian AR, Mehdipour P. A meta-analysis on concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) to detect HER2 gene overexpression in breast cancer. Breast Cancer 2015; 22(6): 615-25.
مجله دانشکده پزشکی اصفهان
دوره 33، شماره 366 - شماره پیاپی 366
بهمن و اسفند 1394
صفحه 2321-2326

فایل ها

سابقه مقاله

  • تاریخ دریافت: 19 آذر 1393
  • تاریخ بازنگری: 08 اردیبهشت 1403
  • تاریخ پذیرش: 17 فروردین 1401

هم رسانی

ارجاع به این مقاله

آمار