Please use this identifier to cite or link to this item:
標題: 荷爾蒙受器、KIT及HER-2於犬肥大細胞瘤之表現
Expressions of hormone receptors, KIT and HER-2 in canine mast cell tumor
作者: 郭俞麟
Kuo, Yu-Lin
關鍵字: canine mast cell tumor
hormone receptors
出版社: 獸醫學系暨研究所
引用: Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 1998; 11: 155-168. Ayl RD, Couto CG, Hammer AS, Weisbrode S, Ericson JG, Mathes L. Correlation of DNA ploidy to tumor histologic grade, clinical variables, and survival in dogs with mast cell tumors. Vet Pathol 1992 ; 29: 386-390. Baral E, Nagy E, Kangas L, Berczi I. Anti-estrogens enhance the therapeutic effect of lymphokine-activated killer cells on the P815 murine mastocytoma. Int J Cancer 1996; 67: 580-585. Bostock DE. The prognosis following surgical removal of mastcytoma in dogs. J Small Anim pract 1973; 14: 27-40. Bozionellou V, Mavroudis D, Perraki M, Papadopoulos S, Apostolaki S, Stathopoulos E, Stathopoulou A, Lianidou E, Georgoulias V. Trastuzumab administration can effectively target chemotherapy- resistant cytokeratin-19 messenger RNA-positive tumor cells in the peripheral blood and bone marrow of patients with breast cancer. Clin Cancer Res 2004; 10: 8185-8194. Cahill DW, Bashirelahi N, Solomon LW, Dalton T, Salcman M, Ducker TB. Estrogen and progesterone receptors in meningiomas. J Neurosurg 1984; 60: 985- 993. Chabot B, Stephenson DA, Chapmen VM, Besmer P, Bernstein A. The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature 1988; 335:88-89. de las Mulas JM, Millan Y, Dios R. A prospective analysis of immunohistochemically determined estrogen receptor alpha and progesterone receptor expression and host and tumor factors as predictors of disease-free period in mammary tumors of the dog. Vet Pathol 2005; 42: 200- 212. de las Mulas JM, Ordas J, Millan Y, Fernandez-Soria V, Ramon y Cajal S. Oncogene HER-2 in canine mammary gland carcinomas: an immunohistochemical and chromogenic in situ hybridization study. Breast Cancer Res Treat 2003; 80: 363- 367. Dugan MC, Dergham ST, Kucway R, Singh K, Biernat L, Du W, Vaitkevicius VK, Crissman JD, Sarkar FH. HER-2/neu expression in pancreatic adenocarcinoma: relation to tumor differentiation and survival. Pancreas 1997; 14: 229- 236. Elling H, Ungemach FR. Sexual hormone receptors in canine mast cell tumour cytosol. J Comp Path 1982; 92: 629- 630. Finnie JW, Bostock DE. Skin neoplasia in dogs. Aust Vet J 1979; 55: 602- 604. Furitsu T, Tsujimura T, Tono T, Ikeda H, Kitayama H, Koshimizu U, Sugahara H, Butterfield JH, Ashman LK, Kanayama Y, et al. Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product. J Clin Invest 1993; 92: 1736- 1744. Gerritsen RJ, Teske E, Kraus JS, Rutteman GR. Multi-agent chemotherapy for mast cell tumours in the dog. Vet Q 1998; 20: 28- 31. Goldschmidt MH, Hendrick MJ. Tumors of the skin and soft tissue. In: Meuton DJ ed. Tumors in domestic animals. 4th ed. Iowa: Iowa state press, 2002, 45- 118. Harvey JM, Clark GM, Osborne CK, Allred DC. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 1999; 17: 1474- 1481. Huang E, Nocka K, Beier DR, Chu TY, Buck J, Lahm HW, Wellner D, Leder P, Besmer P. The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell 1990; 63: 225- 233. Kilpatrick SE, Geisinger KR, King TS, Sciarrotta J, Ward WG, Gold SH, Bos GD. Clinicopathologic analysis of HER-2/neu immunoexpression among various histologic subtypes and grades of osteosarcoma. Mod Pathol 2001; 14: 1277- 1283. Kitamura Y, Go S, Hatanaka K. Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation. Blood 1978; 52: 447- 452. Kitamura Y, Go S. Decreased production of mast cells in Sl/Sld anemic mice. Blood 1979; 53: 492- 497. Kitayama H, Kanakura Y, Furitsu T, Tsujimura T, Oritani K, Ikeda H, Sugahara H, Mitsui H, Kanayama Y, Kitamura Y, Matsuzawa Y. Constitutively activating mutations of c-kit receptor tyrosine kinase confer factor-independent growth and tumorigenicity of factor-dependent hematopoietic cell lines. Blood 1995; 85: 790- 798. Kiupel M, Webster JD, Kaneene JB, Miller R, Yuzbasiyan-Gurkan V. The use of KIT and tryptase expression pattern as prognostic tools for canine cutaneous mast cell tumors. Vet pathol 2004; 41: 371- 377. Kiupel M, Webster JD, Miller RA, Kaneene JB. Impact of tumor depth, tumor location and multiple synchronous masses on the prognosis of canine cutaneous mast cell tumors. J Vet Med A Physiol Pathol Clin Med. 2005; 52: 280- 286. Kolar Z, Ehrmann J Jr, Duskova M. Immunohistochemical analysis of the functional status of estrogen receptor cascade in breast cancer. Neoplasma 1998; 45: 83- 87. Kravis LD, Vail DM, Kisseberth WC, Ogilvie GK, Volk LM. Frequency of argyrophilic nucleolar organizer regions in fine-needle aspirates and biopsy specimens from mast cell tumors in dogs. J Am Vet Med Assoc 1996; 209: 1418- 1420. Lennert K, Parwaresch MR. Mast cell and mast cell neoplasia: a review. Histopathol 1979; 3: 349- 365. London CA, Galli SJ, Yuuki T, Hu ZQ, Helfand SC, Geissler EN. Spontaneous canine mast cell tumors express tandem duplications in the proto-oncogene c-kit. Exp Hematol 1999; 27: 689- 697. London CA, Hannah AL, Zadovoskaya R, Chien MB, Kollias-Baker C, Rosenberg M, Downing S, Post G, Boucher J, Shenoy N, Mendel DB, McMahon G, Cherrington JM. Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies. Clin Cancer Res 2003; 9: 2755- 2768. London CA, Kisseberth WC, Galli SJ, Geissler EN, Helfand SC. Expression of stem cell factor receptor (c-kit) by the malignant mast cells from spontaneous canine mast cell tumours. J Comp Pathol 1996; 115: 399- 414. Macy DW. Canine mast cell tumors. Vet Clin North Am Small Pract 1985; 15: 783- 803. Macy DW. Canine mast cell tumors. In: Withrow SJ, MacEwen EG, eds. Clinical veterinary oncology. Philadelphia: JB Lippincott Co, 1989; 156- 166. Mandara MT, Ricci G, Rinaldi L, Sarli G, Vitellozzi G. Immunohistochemical identification and image analysis quantification of oestrogen and progesterone receptors in canine and feline meningioma. J Comp Pathol 2002; 127: 214- 218. McCaw DL, Miller MA, Bergman PJ, Withrow SJ, Moore AS, Knapp DW, Fowler D, Johnson JC. Vincristine therapy for mast cell tumors in dogs. J Vet Intern Med 1997; 11: 375- 378. Moriello KA, Rosenthal RC. Clinical approach to tumors of the skin and subcutaneous tissues. Vet Clin North Am Small Anim Pract 1990; 20: 1163- 1190. Morini M, Bettini G, Preziosi R, Mandrioli L. C-kit gene product (CD117) immunoreactivity in canine and feline paraffin sections. J Histochem Cytochem 2004; 52: 705- 708. Murua Escobar H, Becker K, Bullerdiek J, Nolte I. The canine ERBB2 gene maps to a chromosome region frequently affected by aberrations in tumors of the dog (Canis familiaris). Cytogenet Cell Genet 2001; 94: 194- 195. O''Keefe DA. Canine mast cell tumors. Vet Clin North Am Small Anim Pract 1990; 20: 1105- 1115. Pardanani A, Akin C, Valent P. Pathogenesis, clinical feature, and treatment advance in mastocytosis. Best Pract Res Clin Haematol 2006; 19: 595- 615. Patnaik AK, Ehler WJ, MacEwen EG. Canine cutaneous mast cell tumor: 35 morphologic grading and survival time in 83 dogs. Vet pathol 1984; 21: 469- 474. Potti A, Willardson J, Forseen C, Kishor Ganti A, Koch M, Hebert B, Levitt R, Mehdi SA. Predictive role of HER-2/neu overexpression and clinical features at initial presentation in patients with extensive stage small cell lung carcinoma. Lung Cancer 2002; 36: 257- 261. Priester WA. Skin tumors in domestic animals: data from 12 United States and Canadian colleges of veterinary medicine. J Natl Cancer Inst 1973; 50: 457- 466. Pryer NK, Lee LB, Zadovaskaya R, Yu X, Sukbuntherng J, Cherrington JM, London CA. Proof of target for SU11654: inhibition of KIT phosphorylation in canine mast cell tumors. Clin Cancer Res 2003; 9: 5729- 5734. Rassnick KM, Moore AS, Williams LE, London CA, Kintzer PP, Engler SJ, Cotter SM. Treatment of canine mast cell tumors with CCNU (lomustine). J Vet Intern Med 1999; 13: 601- 605. Roh H, Pippin J, Drebin JA. Down-regulation of HER2/neu expression induces apoptosis in human cancer cells that overexpress HER2/neu. Cancer Research. 2000; 60: 560- 565. Rothwell TL, Howlett CR, Middleton DJ, Griffiths DA, Duffs BC. Skin neoplasms of dog in Sydney. Aust Vet J 1987; 64: 161- 164. Reguera MJ, Ferrer L, Rabanal RM. Evaluation of an intron deletion in the c-kitgene of canine mast cell tumors. Am J Vet Res 2002; 63: 1257- 1261. Reguera MJ, Rabanal RM, Puigdemont A, Ferrer L. Canine mast cell tumors express stem cell factor receptor. Am J Dermatopathol 2000; 22: 49- 54. Sato O, Wada T, Kawai A, Yamaguchi U, Makimoto A, Kokai Y, Yamashita T, Chuman H, Beppu Y, Tani Y, Hasegawa T. Expression of epidermal growth factor receptor, ERBB2 and KIT in adult soft tissue sarcomas: a clinicopathologic study of 281 cases. Cancer 2005; 103: 1881- 1890. Séguin B, Leibman NF, Bregazzi VS, ORgilvie GK, Powers BE, Dernell WS, Fettman MJ, Withrow SJ. Clinical outcome of dogs with grade-II mast cell tumors treated with surgery alone: 55 cases (1996- 1999). J Am Vet Med Assoc 2001; 218: 1120- 1123. Séguin B, Besancon MF, McCallan JL, Dewe LL, Tenwolde MC, Wong EK, Kent MS. Recurrence rate, clinical outcome, and cellular proliferation indices as prognostic indicators after incomplete surgical excision of cutaneous grade II mast cell tumors: 28 dogs (1994- 2002). J Vet Intern Med 2006; 20: 933- 940. Simoes JPC, Schoning P, Butine M. Prognosis of canine mast cell tumors: A comparison of three methods. Vet Pathol 1994; 31: 637- 647. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989; 244: 707- 712. Speciale J, Koffman B, Bashirelahi N, Steinberg S. Identification of gonadal steroid receptors in meningiomas from dogs and cats. Am J Vet Res 1990; 51: 833- 835. Takahashi T, Kadosawa T, Nagase M, Matsunaga S, Mochizuki M, Nishimura R, Sasaki N. Visceral mast cell tumors in dogs: 10 cases (1982-1997). J Am Vet Med Assoc 2000; 216: 222- 226. Tams TR Macy DW. Canine mast cell tumors. Compend Cont Educ Pract Vet 1981; 27: 259- 263. Thamm DH, Mauldin EA, Vail DM. Prednisone and vinblastine chemotherapy for canine mast cell tumor--41 cases (1992-1997). J Vet Intern Med 1999; 13: 491- 497. Thamm DH, Vail DM. Mast cell tumors. In: Withrow SJ, MacEwen EG eds. Small animal clinical oncology, 3rd ed. Philadelphia: WB Saunders Co, 2001; 261- 282. Tsujimura T, Furitsu T, Morimoto M, Isozaki K, Nomura S, Matsuzawa Y, Kitamura Y, Kanakura Y. Ligand-independent activation of c-kit receptor tyrosine kinase in a murine mastocytoma cell line P-815 generated by a point mutation. Blood 1994; 83: 2619- 2626. Tsujimura T, Furitsu T, Morimoto M, Kanayama Y, Nomura S, Matsuzawa Y, Kitamura Y, Kanakura Y. Substitution of an aspartic acid results in constitutive activation of c-kit receptor tyrosine kinase in a rat tumor mast cell line RBL-2H3. Int Arch Allergy Immunol 1995; 106: 377- 385. Turrel JM, Kitchell BE, Miller LM, Theon A. Prognostic factors for radiation treatment of mast cell tumor in 85 dogs. J Am Vet Med Assoc 1988; 193: 936- 940. Van Pelt DR, Fowler JD, Leighton FA. Multiple cutaneous mast cell tumors in a dog: A case report and brief review. Canadian Vet J 1986; 27: 259- 263. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ, Press M. 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- 726. Webster JD, Kiupel M, Yuzbasiyan-Gurkan V. Evaluation of the kinase domain of c-KIT in canine cutaneous mast cell tumors. BMC Cancer 2006; 6: 85- 92.. Webster JD, Yuzbasiyan-Gurkan V, Kaneene JB, Miller R, Resau JH, Kiupel M. The role of c-KIT in tumorigenesis: evaluation in canine cutaneous mast cell tumors. Neoplasia 2006; 8: 104- 111. Yamashita H, Ando Y, Nishio M, Zhang Z, Hamaguchi M, Mita K, Kobayashi S, Fujii Y, Iwase H. Immunohistochemical evaluation of hormone receptor status for predicting response to endocrine therapy in metastatic breast cancer. Breast Cancer 2006; 13: 74- 83. Zemke D, Yamini B, Yuzbasiyan-Gurkan V. Mutations in the Juxtamembrane Domain of c-KIT Are Associated with Higher Grade Mast Cell Tumors in Dogs. Vet Pathol 2002; 39: 529- 535. Zsebo KM, Wypych J, McNiece IK, Lu HS, Smith KA, Karkare SB, Sachdev RK, Yuschenkoff VN, Birkett NC, Williams LR, et al. Identification, purification, and biological characterization of hematopoietic stem cell factor from buffalo rat liver--conditioned medium. Cell 1990; 63: 195- 201.
摘要: 肥大細胞瘤是犬隻常見的腫瘤之一,其發生率約佔犬皮膚及皮下腫瘤的7%至21%。 肥大細胞瘤的預後差異性極大,有很多預後因子曾被研究。 其中腫瘤細胞的分級 (grading) 是目前公認與預後最有關聯性的預測因子。 性別對於肥大細胞瘤預後的影響曾被研究過但沒有明確的定論。 動情素受器 (ER) 及黃體素受器 (PR) 的表現在乳腺腫瘤的研究最為透徹,ER及PR的表現被認為是良好的預後因子。 ER及PR在犬肥大細胞瘤曾被發現過。 HER-2蛋白在人類乳癌及其他來源的惡性腫瘤中被發現過度表現,HER-2蛋白的過度表現會使得細胞的分裂及增值加快,進而導致腫瘤侵襲性變強。 KIT蛋白過度表現在人及狗的肥大細胞增生或腫瘤已被確認,但 本實驗對象是1999年至2006年6月間於國立中興大學獸醫教學醫院治療之肥大細胞瘤患犬,利用免疫組織化學染色法針對ER、PR、HER-2蛋白及KIT蛋白表現進行評估,並探討其臨床意義。 實驗結果顯示,20 % (4/20) 的樣本呈現PR陽性反應,但所有樣本之腫瘤細胞核均呈現ER陰性反應。 35 % (7/20) 之樣本其腫瘤細胞質呈現ER陽性反應,推測可能為無功能性之ER。 HER-2蛋白在本實驗的樣本中均未發現。 KIT蛋白在95 % (19/20) 的樣本中呈現陽性反應,其在腫瘤細胞內之分布與腫瘤細胞分化之程度有關聯。 依據本實驗之結果,並未發現將針對ER及HER-2蛋白之化學療法應用於肥大細胞瘤患犬隻之直接證據。 PR之表現與肥大細胞瘤致病機轉之關係仍需進一步研究。
Mast cell tumor (MCT) is one of the most common tumors in dogs, accounting for approximately 7 %- 21 % of canine cutaneous and subcutaneous neoplasms. Prognosis of MCT varies from case to case, therefore plenty of predictors were evaluated. Histological grading is considered the most powerful prognostic parameter up to date . Sex predisposition has been studied but remains controversial. The expressions of estrogen receptors (ER) and progesterone receptors (PR) have been widely studied in mammary gland tumors both in human and canine and are confirmed to be good prognosticators. ER and PR were found in canine MCTs according to a literature published in 1982. Over-expressions of HER-2 were found in several kinds of human and canine neoplasms including breast cancer and some soft tissue sarcoma of mesenchymal origins. The aim of this study is to determine the expressions of ER, PR, HER-2 and KIT immunohistochemically and to evaluate the consequencing clinical relevance. Samples were collected from NCHU-VMTH between 1999 and June of 2006. Each sample was examined histopathologically with routine H&E stain and four immunohistochemical methods that detect ER, PR HER-2 and KIT, respectively. 20 cases met the criteria of sample colleting and were enrolled in this study. 4 out of 20 (20 %) samples were PR- positive, but none of the nuclei of all 20 specimens was stained positive of ER. ER-positive staining was found in the cytoplasm of seven samples (35%). This phenomenon implied the expression of non-functioning ER present in cytoplasm of MCT cells. KIT protein was found in 95 % of samples. The IHC staining pattern was related to the histological grading of tumor cells. Because either ER or HER-2 were not expressed in all of the samples in this study, the use of chemotherapy against ER or HER-2 would not be suggested to be applied to MCT patients. The relationship between the expression of PR and pathogenesis of MCT requires further investigation.
其他識別: U0005-0702200716591300
Appears in Collections:獸醫學系所



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.