Ebru ARABACI, Gülay BİLİR, Işın PAK, Ali E. DEMİRBAĞ

131 invaziv duktal karsinom olgusunda, C-ERBB-2 artmış ekspresyonunun, histopatolojik ve immünhistokimyasal prognostik faktörlerle karşılaştırılması

C-erbB-2 onkogeni, p185 olarak bilinen, epidermal büyüme faktörü ailesine ait, tirozin kinaz aktiviteli bir transmembran glikoproteinini kodlar. Meme kanserinde c-erbB-2' nin artmış ekspresyonu kötü prognozla ilişkilidir. Bu çalışmada, 131 invaziv duktal karsinom vakasına ait parafin doku kesitleri incelendi. C-erbB-2 artmış ekspresyonu ile diğer prognostik belirleyiciler (yaş, tümör boyutu, lenf nodu tutulumu, tümör grade' i, lenfovasküler invazyon, nöral invazyon, ekstensif intraduktal karsinom, östrojen ve progesteron reseptör statüsü, p53) arasındaki ilişki değerlendirildi. Sonuçlarımız, c-erbB-2 artmış ekspresyonunun yaş (p=0.02), tümör grade'i( p=0.001), östrojen reseptörü (p=0.017), p53 (p=0.047) ile istatiksel olarak ilişkili olduğunu gösterdi. Bu çalışma, c-erbB-2 onkogeninin, meme kanserinde, diğer klinikopatolojik-moleküler faktörlerle ilişkili önemli bir biyolojik belirleyici olduğunu göstermiştir.

Anahtar Kelimeler:

Onkojen proteinler v-erbB, İmmünohistokimya, Seyir, Reseptör, epidermal büyüme faktörü, Biyolojik belirteçler, Reseptör, erbB-2, Genler, erbB-2, Karsinom, kanal

Correlation of C-ERBB-2 overexpression with histopathologic and immunohistochemical prognostic factors in 131 invasive ductal carcinoma cases

C-erbB-2 oncogene, encodes a transmembran glycoprotein with tyrosine kinase activity known as p185, which belongs to the family of epidermal growth factors. Its overexpression in breast cancer has been correlated with poor prognosis. In this study, paraffin-embedded tumor sections from 131 invasive ductal carcinoma cases were analyzed . The relationship between c-erbB-2 overexpression and other prognostic markers (age, tumor size, lymph node involvement, tumor grade, lymphovascular invasion, neural invasion, extensive intraductal carcinoma, estrogen, progesteron receptor status and p53) were examined. Our results showed that, c-erbB-2 overexpression is statistically correlated with age (p=0.02), tumor grade (p=0.001), estrogen receptor (p=0.0017) and p53 (p=0.047). This study confirmed that c-erbB-2 oncogene, related to other clinicopathological-molecular factors, is an important biologic marker in breast cancer.

Keywords:

Oncogene Proteins v-erbB, Immunohistochemistry, Prognosis, Receptor, Epidermal Growth Factor, Biological Markers, Receptor, erbB-2, Genes, erbB-2, Carcinoma, Ductal,

PDF

___

1. Dawkins HJS, Robbins PD, Smith KL, et al. What’s new in breast cancer? Molecular perspectives of cancer development and the role of the oncogene c-erb-2 in prognosis and disease Path. Res. Pract. 1993; 189: 1233-1252.
2. Yosef Yarden. Biology of HER2 and its importance in breast cancer, Oncology 2001; 61(suppl 2):1-13.
3. Ross JS, Fletcher JA, Linette GP, et al. The HER-2/neu gene and protein in breast cancer 2003: Biomarker and Target of therapy. The Oncologist 2003;8(4):307-325.
4. Rubin I, Y. Yarden. The basic biology of HER2, Symposium Article. Annals of Oncology, 2001; 2:127-137.
5. Caroline Lohrisch, Martine Piccard. An overview of HER-2. Seminars in Oncolgy 2001;28(no 6 suppl 18): 3-11.
6. Holbro T, Civenni G, Hynes NE. The ErbB receptors and their role in cancer progression. Experimental Cell Research 2003;284:99-110.
7. Dowsett M, Cooke T, Ellis I, et al. Assesment of HER 2 status in breast cancer: why, when and how?. European Journal of Cancer 2000;36:170-176.
8. 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; 235:177-182.
9. Daniel F. Hayes, Ann D. Thor. C-erbB-2 in breast cancer: Development of a clinically useful marker, Seminars in Oncology, 2002;29(3): 231-245.
10. Pietras R, Arboleda J, Reese D, et al. HER-2 tyrosine kinase patway targets estrogen receptor and promotes hormoneindependent growth in human breast cancer cells. Oncogene 1995; 10: 2435- 2446.
11. Pauletti G, Godolphin W, Slamon DJ et al.: detection and quantitation of HER- 2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization. Oncogene 1996; 13:63-72.
12. Wedad Hanna. Testing for HER-2 status . Oncology 2001; 61(suppl 2); 22-30.
13. Larsımont D, Leo A, Rouas G, et al. HER-2/neu evaluation by immunohistochemistry and fluorescence in situ hibridization in breast cancer: Implications for daily laboratory practice. Anticancer Research 2002;22:2485-2490.
14. Vijver M. Emerging tecnologies for HER-2 testing. Oncology 2002; 63 (suppl 1): 33-38.
15. Isaacs C, Stearns V, Hayes D. New prognostic factors for breast cancer recurrence. Seminars in Oncology 2001;28:53-67.
16. 16. N.J.Bundred. Prognostic and Predictive Factors in Breast cancer. Cancer Treatment Reviews 2001; 27: 137-142.
17. RLH. Jansen. Prognostic and predictive factors in breast cancer. Netherlands Journal of Medicine 1997; 51.65-77.
18. Stamatina Kaptain, Lee K. Tan, Beiyun Chen. Her-2/neu and Breast cancer. Diagnostic Molecular Pathology 2001;10(3): 139-152.
19. Tervahauta A, Eskelinen M, Syrjanen S, et al. Immunohistochemical demonstration of c-erbB-2 oncoprotein expression in female breast cancer and its prognostic significance. Anticancer Res. 1991;11: 1677-1682.
20. Borg A, Baldetorp B, Fernö M, et al. ERBB2 amplification in breast cancer with high rate of proliferation. Oncogene 1991; 6: 137-143.
21. Tavassoli FA. Pathology of the Breast. 2nd. Ed., Hong Kong: Mc Graw-Hill Company, 1999.
22. Juan Rosai. Rosai and Ackerman’s Surgical Pathology. Ninth Ed. Vol. 2, Mosby. 2004.
23. Marx D, Schauer A, Reiche C, et al. C-erbB-2 expression in correlation to other biological parameters of breast cancer. J Cancer Res Clin Oncol 1990; 116: 15-20.
24. Jukkola A, Bloigu R, Soini Y et al. C-erbB-2 positivity is a factor for poor prognosis in breast cancer and poor response to hormonal or chemotherapy treatment in advanced disease. European Journal of Cancer 2001; 37: 347-354.
25. Saceda M, Grunt TW, Colomer R, et al. Regulation of estrogen receptor concentration and activity by an erB/HER ligand in breast carcinoma cell lines. Endocrinology 1996; 137: 4322-4330.
26. Fuqya SA, Fitzgerald SD, Allred DC. Inhibition of estrogen receptor action by a naturally occuring variant in human breast tumors. Cancer Res. 1992;52.483-486.
27. Querzoli P, Marchetti E, Fabris G, et al. Immunohistochemical expression of c-erbB-2 in human breast cancer by monoclonal antibody: correlation with lymph node and ER status. Tumori 1990; 76: 461-464.
28. Barbati A, Cosmi EV, Sidoni A, et al. Value of c-erbB-2 and p53 oncoprotein co-overexpression in human breast cancer.Anticancer Res. 1997; 17: 401-406.
29. Barbereshi M, Leonardi E, Mauri F, et al. P53 and c-erbB-2 protein expression in breast carcinomas. An immunohistochemical study including correlations with receptor status, proliferation markers, and clinicalstage in human breast cancer. Am J Clin Pathol 1992; 98: 408-418.
30. Beenken SW, Grizzle WE, Crowe RD, et al. Molecular biomarkers for breast cancer prognosis: coexpression of c-erbB-2 and p53. Annals of Surgery 2001; 233(5):630-638.
31. Jing X, Kakudo K, Murakami M, et al. Intraduktal spread of invasive breast carcinoma has a positive correlation with c-erbB-2 overexpression and vascular invasion Cancer 1999; 86(3);439-448
32. Rilke F, Colgagni MI, Cascinelli N et al. Prognostic significance of HER-2/neu expression in breast cancer and its relationship to other prognostic factors. Int J Cancer 1991; 49: 44-49.