생명과학회지 (Journal of Life Science)

  • 제18권1호
  • /
  • Pages.16-22
  • /
  • 2008
  • /
  • 1225-9918(pISSN)
  • /
  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
권호 표지
DOI QR코드

DOI QR Code

HER-2/neu 단백질이 개 유방암에서의 발현분석

HER-2/neu Protein Expression in Canine Mammary Adenocarcinoma

  • 양해걸 (경북대학교 수의과대학 병리학교실) ;
  • 도선희 (건국대학교 수의과대학 임상병리학교실) ;
  • 위엔동웨이 (경북대학교 수의과대학 병리학교실) ;
  • 홍일화 (경북대학교 수의과대학 병리학교실) ;
  • 기미란 (경북대학교 수의과대학 병리학교실) ;
  • 박진규 (경북대학교 수의과대학 병리학교실) ;
  • 구문정 (경북대학교 수의과대학 병리학교실) ;
  • 이혜림 (경북대학교 수의과대학 병리학교실) ;
  • 홍경숙 (경북대학교 수의과대학 병리학교실) ;
  • 황옥경 (경북대학교 수의과대학 병리학교실) ;
  • 한정연 (경북대학교 수의과대학 병리학교실) ;
  • 박호용 ;
  • 유성은 (한국화학연구원) ;
  • 정규식 (경북대학교 수의과대학 병리학교실)
  • Yang, Hai-Jie (Department of Veterinary Pathology, Collage of Veterinary Medicine, Kyungpook National University) ;
  • Do, Sun-Hee (Department of Clinical Pathology, College of Veterinary Medicine, Konkuk University) ;
  • Yuan, Dong-Wei (Department of Veterinary Pathology, Collage of Veterinary Medicine, Kyungpook National University) ;
  • Hong, Il-Hwa (Department of Veterinary Pathology, Collage of Veterinary Medicine, Kyungpook National University) ;
  • Ki, Mi-Ran (Department of Veterinary Pathology, Collage of Veterinary Medicine, Kyungpook National University) ;
  • Park, Jin-Kyu (Department of Veterinary Pathology, Collage of Veterinary Medicine, Kyungpook National University) ;
  • Goo, Moon-Jung (Department of Veterinary Pathology, Collage of Veterinary Medicine, Kyungpook National University) ;
  • Lee, Hye-Rim (Department of Veterinary Pathology, Collage of Veterinary Medicine, Kyungpook National University) ;
  • Hong, Kyung-Sook (Department of Veterinary Pathology, Collage of Veterinary Medicine, Kyungpook National University) ;
  • Hwang, Ok-Kyung (Department of Veterinary Pathology, Collage of Veterinary Medicine, Kyungpook National University) ;
  • Han, Jung-Youn (Department of Veterinary Pathology, Collage of Veterinary Medicine, Kyungpook National University) ;
  • Park, Ho-Yong (Insect Biotec Co., Ltd.) ;
  • Yoo, Sung-Eun (KOREA Research Institute of Chemical Technology) ;
  • Jeong, Kyu-Shik (Department of Veterinary Pathology, Collage of Veterinary Medicine, Kyungpook Nationadjl University)
  • 발행 : 2008.01.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

개에서의 유선 종양진단은 총 49 case 중에서 Human epidermal growth factor receptor (HER-2/neu, c-erbB-2), Epidermal growth factor receptor (EGFR), Activated leukocyte cell adhesion molecule (ALCAM) 등 면역조직화학적염색법을 실시하였다. 우선 49 case를 두 그룹으로 즉: 양성종양그룹 (22 case)과 악성종양그룹 (27 case)으로 구분하였다. 면역조직화학적염색법의 분석결과 HER-2/neu의 발현은 양성종양에서는 31.8% (7/22), 악성종양에서는 29.6% (8/27)의 발현율을 보였고, EGFR의 발현은 양성종양에서는 27.3% (6/22), 악성종양에서는 22.2% (6/27)의 발현율을 보였으며, ALCAM의 발현은 양성종양에서는 40.9% (9/22), 악성종양에서는 7.4% (2/27)의 발현율을 보였다. 결론적으로 개에서의 유선종양진단의 발현율은 사람에서 보고된 것($25%{\sim}30%$)과 비슷하게 나타났으며 임상진단분야에서 HER-2/neu항체로 개에서의 유선종양진단에서 유용한 평가수단으로 적용될 수 있으리라 사료된다.

In this study to evaluate the involvement of EGFR, HER-2/neu and ALCAM (CD166) oncogene products in canine mammary neoplastic lesions, sections of archived paraffin-embedded samples of 49 mammary tumors were analyzed immunohistochemically using antibodies against human EGFR and HER-2/neu and ALCAM. These 49 tumors were divided into 2 groups: 22 benign (19 adenoma, 3 benign mixed tumors) and 27 malignant tumors (2 simple adenocarcinomas, 5 complex adenocarcinomas, 3 solid carcinoma, 5 sclerosing carcinoma, 8 malignant mixed tumors and 4 malignant myoepithelioma). As a result of immunostaining, 31.8% (7/22) of the benign tumors and 29.6% (8/27) of the malignant tumors expressed the HER-2/neu oncogene product, EGFR expression was detected in 27.3% (6/22) of benign tumors and in 22.2% (6/27) of the malignant tumors. ALCAM expression was detected in 40.9% (9/22) of benign tumors and in 7.4% (2/27) of the malignant tumors. These results suggest that some of the biological and morphological characteristics of the tumor are associated with canine mammary gland tumors, as also reported for human breast cancer, the possibility of using anti-HER-2/neu antibodies in the treatment of canine mammary tumors.

키워드

참고문헌

  1. Ahern, T. E., R. C. Bird, A. E. Church Bird and L. G. Wolfe. 1996. Expression of the oncogene c-erbB-2 in canine mammary cancers and tumor-derived cell lines. Am. J. Vet. Res. 57, 693-696.
  2. Ali, I. U., G. Campbell and R. Lidereau. 1988. Amplification of c-erbB-2 and aggressive human breast tumors? Science. 240, 1795-1798. https://doi.org/10.1126/science.3289120
  3. Anudep, RUNGSIPIPAT., TATEYAMA. Susumu, YAMAGUCHI. Ryoji, UCHIDA. Kazuyuki, MIYOSHI. Noriaki and HAYASHI. Toshiharu. 1999. Immunohistochemical analysis of c-yes and c-erbB-2 oncogene products and p53 tumor suppressor protein in canine mammary tumors. J. Vet. Med. Sci. 61(1), 27-32. https://doi.org/10.1292/jvms.61.27
  4. Arai, F., O. Ohneda, T. Miyamoto, X. Zhang and T. Suda. 2002. Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion molecule and participate in bone marrow formation. J. Exp. Med. 195, 1549-1563. https://doi.org/10.1084/jem.20011700
  5. Bartkova, J., D. M. Barnes, R. R. Millis and W. J. Gullick. 1990. Immunohistochemical demonstration of c-erbB-2 protein in mammary ductal carcinoma in situ. Human. Pathology 21, 1164-1167. https://doi.org/10.1016/0046-8177(90)90154-W
  6. Bowen, M. A, D. D. Patel, X. Li, B. Modrell, A. R. Malacko, W. C. Wang, H. Marquardt, M. Neubauer, J. M. Pesando, U. Francke, B. F. Haynes and A Aruffo. 1995. Cloning, mapping, and characterization of activated leukocyte-cell adhesion molecule (ALCAM), a CD6 ligand. J. Exp. Med. 181, 2213-2220. https://doi.org/10.1084/jem.181.6.2213
  7. Brodey, R. S., M. H. Goldschmidt and J. R. Roszel. 1983. Canine mammary gland neoplasms. J. Am. Anim. Hosp. Assoc. 19, 61-90.
  8. Corbel, C., H. G. Bluestein, O. Pourquie, P. Vaigot and N. M. Le Douarin. 1992. An antigen expressed by avian neuronal cells is also expressed by activated T lymphocytes. Cell. Immunol. 141, 99-110. https://doi.org/10.1016/0008-8749(92)90130-H
  9. Degen, W., L. Kempen, E. Gijzen, J. van Groningen, Y. van Kooyk, H. Bloemers and G. Swart. 1998. MEMD, a new cell adhesion molecule in metastasizing human melanoma cell lines, is identical to ALCAM (activated leukocyte cell adhesion molecule). Am. J. Pathol. 152, 805-813.
  10. Fidler, I. J. and R. S. Brodey. 1967. A necropsy study of canine malignant mammary neoplasm. J. Am. Vet. Med. Assoc. 151, 710-715.
  11. Gullick, W. J. 1990. The role of the epidermal growth factor receptor and the c-erbB-2 protein in breast cancer. Int. J. Cancer. 5, 55-66. https://doi.org/10.1002/ijc.2910050108
  12. Harris, C. C. and M. Hallstein. 1993. Clinical implication of the p53 tumor suppressor gene. New. Engl. J. Med. 329, 1318-1327. https://doi.org/10.1056/NEJM199310283291807
  13. King, J. A., S. F. Ofori-Acquah, T. Stevens, A. B. AI-mehdi, O. Fodstad and W. G. Jiang. 2004. Activated leukocyte cell adhesion molecule in breast cancer: Prognostic indicator. Breast Cancer Res. 6, R478-R487. https://doi.org/10.1186/bcr815
  14. Klijn, J. G., P. M. Berns, P. I. Schmitz and J. A Foekens. 1992. The clinical significance of epidermal growth factor receptor (EGF-R) in human breast cancer: a review of 5232 patients. Endocr. Rev. 13, 3-17.
  15. Krupp, M. N., D. T. Connolly and M. D. Lane. 1982. Synthesis, turnover and down-regulation of epidermal growth factor receptors in human A431 epidermal carcinoma cells and skin fibroblasts. J. Biol. Chem. 257, 11489-11496.
  16. Lacroix, H., J. D. Iglehart, M. A. Skinner and M. H. Kraus. 1989. Overexpression of erbB-2 or EGF receptor proteins present in early stage mammary carcinoma is detected simultaneously in matched primary tumors and regional metastases. Oncogene 4, 145-151.
  17. Miller, W. R., M. O. Ellis, J. R. C. Sainsbury and J. M. Dixon. 1994. Prognostic factors ABC of breast disease. Br. Med. J. 309, 1573-1576. https://doi.org/10.1136/bmj.309.6968.1573
  18. Moller, P., G. Mechtersheimer, M. Kaufmann, G. Moldenhauer, F. Momburg and T. Mattfeldt. 1989. Expression of epidermal growth factor receptor in benign and malignant primary tumours of the breast. Virchows. Arch. [Pathol. Anat.] 414, 157-164. https://doi.org/10.1007/BF00718595
  19. Nakopoulou, L. L., A. Alexiadou, G. E. Theodoropoulos, A. C. H. Lazaris, A. Tzonou and A. Keramopoulos. 1996. Prognostic significance of the co-expression of p53 and c-erbB-2 protein in breast cancer. J. Pathol. 179, 31-38. https://doi.org/10.1002/(SICI)1096-9896(199605)179:1<31::AID-PATH523>3.0.CO;2-O
  20. Nicholson, R. I., R. A. McClelland, J. M. W. Gee, D. L. Manning, P. Cannon, J. F. R. Robertson, I. O. Ellisand R. W. Blamey. 1994. Epidermal growth factor receptor expression in breast cancer: association with responses to endocrine therapy. Breast Cancer Res. Treat. 29, 117-125. https://doi.org/10.1007/BF00666187
  21. Ohneda, O., K. Ohneda, F. Arai, J. Lee, T. Miyamoto, Y. Fukushima, D. Dowbenko, L. A. Lasky and T. Suda. 2001. ALCAM (CD166): its role in hematopoietic and endothelial development. Blood 98, 2134-2142. https://doi.org/10.1182/blood.V98.7.2134
  22. Pauletti, G., S. Dandekar, L. Ramos, H. Peng, R. Seshadri and D. Slamon, 2000. Assessment of methods for tissue-based detection of the HER-2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemisty. J. Clin. Oncol. 18, 3651-3664. https://doi.org/10.1200/JCO.2000.18.21.3651
  23. Rachamandra, S., L. Machin, S. Ashley, P. Monaghan and B. A. Gusterson. 1990. Immunohistochemical distribution of c-erbB-2 in in situ carcinoma: a detailed morphological analysis. J. Path. 161, 7-14. https://doi.org/10.1002/path.1711610104
  24. Rungsipipat, A,, S. Tateyama, R. Yamaguchi, K. Uchida, N. Myoshi and T. Hayashi. 1999. Immunohistochemical analysis of c-yes and c-erbB-2 oncogene products and p53 tumor suppressor protein in canine mammary tumors. J. Vet. Med. Sci. 61, 27-32. https://doi.org/10.1292/jvms.61.27
  25. Rosen, A and I. J. Oberman, 1960. Addiction to phenmetrazine hydrochloride and its psychiatric implications. J. Am. Osteopath. Assoc. 59, 722-726.
  26. Sainsbury, J. R., J. R. Farndon, A. L. Harris and G. V. Sherbet. 1985. Epidermal growth factor receptors on human breast cancers. Br. J. Surg. 72, 186-188. https://doi.org/10.1002/bjs.1800720309
  27. Salomon, D. S., R. Brandt, F. Ciardello and N. Normanno, 1995. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit. Rev. Oncol. Hematol. 19, 183-232. https://doi.org/10.1016/1040-8428(94)00144-I
  28. Schechter, A. L., D. F. Stern, L. Vaidyanathan, S. J. Decker, J. A. Drebin, M. I. Greene and R. A. Weinberg. 1984. The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature 312, 513-516. https://doi.org/10.1038/312513a0
  29. Shih, C., L. C. Padhy, M. Murray and R. A Weinberg. 1981. Transforming genes of carcinomas and neuroblastomas introduced introduced into mouse fibroblasts. Nature 290, 261-264. https://doi.org/10.1038/290261a0
  30. Slamon, D. J., C. M. Clark and S. C. Wong. 1987. Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235, 177-182. https://doi.org/10.1126/science.3798106
  31. Thomas, C. J., W. K. Norval and D. H. Ronald. 1997. Veterinary pathology. pp. 1190-1200, In: Genital system, 6th eds., (Williams & Wilkins) Lippincott Baltimore, Maryland.
  32. Toi, M., T. Tominaga and A. Osaki. 1994. Role of epidermal growth factor receptor expression in primary breast cancer: results of a biochemical study and an immunocytocehmical study. Breast Cancer Res. Treat. 29, 51-58. https://doi.org/10.1007/BF00666181
  33. van Kempen, L. C., J. J. van den Oord, G. N. van Muijen, U. H. Weidle, H. P. Bloeers and G. W. Swart. 2000. Activated leukocyte cell adhesion molecule/CD166, a marker of tumor progression in primary malignant melanoma of the skin. Am. J. Pathol. 156(3), 769-774. https://doi.org/10.1016/S0002-9440(10)64943-7