臺灣博碩士論文加值系統

Abstract

Mammary tumors are the most common tumors in female dogs, and are known for their biologic and histomorphologic heterogeneity. In canine mammary mixed tumors, dominant ectopic cartilage and bone formation accompanied by abundant proliferation of myoepithelial cells is observed frequently, which is a unique features of canine mammary tumors because it was occasionally described in human..
To investigate the histogenesis of cartilage and/or bone in canine mammary tumors, we utilized different immunohistochemical (IHC) markers and histochemial methods in 22 benign and 78 malignant mixed tumors in female dogs. IHC markers included p63, CK14, CK8/18 and vimentin. Histochemical methods included alcian blue and mucicarmine staining was conducted to determine the distribution of cartilage and mucin, respectively. Immunohistochemically, p63-positive cells usually found next to the ectopic cartilage or between the glandular cells and cartilage, and in the connective area of the tubular-papillary type where may develop metaplastic areas. In metaplastic area, large amount of the cells showed reactivity for vimentin. This results showed that there is loss of expression of p63 and cytokeratins in areas of myoepithelial proliferation, and enhanced expression of vimentin protein in proliferative areas with chondroid metaplasia. Therefore, we suggested that ectopic cartilage or bone development followed by metaplasia, which may be triggered by myoepithelial cells, and the mucin substance was used as a medium for development of ectopic cartilage.

表次……………………………………………………...............................................iv
圖次…………………………………………………………….…………...………....v
英文摘要…………………………………………………………………......……….vi
中文摘要…………………………………………………………………………… vii
第一章 緒言…………………………………………................................................1
第二章 文獻探討…………………………………………........................................2
第一節 犬乳腺腫瘤之介紹……………………………................................2
一、 犬乳腺腫瘤之流行病學……………………………................................2
二、 犬乳腺腫瘤之病因學……………………………....................................2
三、 犬乳腺腫瘤之臨床表現及診斷…............................................................4
四、 犬乳腺腫瘤組織病理學診斷…................................................................4
五、 臨床分期……………................................................................................7
第二節 乳腺腫瘤的治療模式…………….…………..………….................8
一、 外科治療…………………………………….……...................................8
二、 其他治療……………………………………….…...................................9
三、 預後因數……………………………………….…...................................9
第三節 犬混合性乳腺瘤探討……………………………………..............10
一、Mammary mixed tumors之組織病理特徵…………….........................10
二、Mammary mixed tumors之組織來源……………….............................11
第四節 免疫組織化學抗體之討論…………………..................................12
一、 p63之介紹………………………………………...................................12
二、 p63之免疫組織化學應用…………………….......................................14
三、 特殊染色與黏液樣物質之介紹………………………..........................16
第三章 材料與方法……………..........................................................................19
第一節 樣本之採集及處理……………………......................................19
一、 犬隻乳腺腫瘤之樣本採集……………………..................................19
二、 腫瘤組織的處理流程…………………….........................................19
三、 抗體來源……………………..............................................................20
第二節 免疫組織化學染色……………………………….…...................21
一、 切片製作及染色前準備………………………...…...........................21
二、 組織之脫蠟及復水…………………………………….….................21
三、 P63之免疫組織化學染色……………………...................................21
四、 CK14、CK8+18、vimentin免疫組織化學染色………………...….....22
第三節 組織化學染色……………………………………………………22
一、 腫瘤組織處理流程及切片製作……………………….….................22
二、 Alcian blue pH 0.4………………………..…..…...............................23
三、 Mucicarmine………………..…………………...................................23
第四節 免疫組織化學染色之評估方式…………………...…...................23
第四章 結果……………..............................................................................................24
第一節、犬乳腺腫瘤組織型態學…………………...................................24
一、 樣本基本資料……………………......................................................24
二、良性混合性乳腺腫瘤(Benign mixed tumors and complex adenoma)
組織型態學分析..................................................................................25
三、 Complex carcinomas組織型態學分析………..………….…… ........26
四、Carcinosarcoma組織型態學分析……..…………….........................27
五、 惡性骨肉瘤(osteosarcoma)及其他特殊型態乳腺瘤組織學分
析…………………………………………………….…….................27
六、 組織病理學討論………………..........................................................28
第二節、 p63免疫組織化學染色結果………………………….........................29
一、p63在benign mixed tumors之表現……………..………......................29
二、p63在complex carcinoma之表現……………..……….........................31
三、p63在carcinosarcoma之表現………………..……...............................33
四、p63在osteosarcoma之表現…………………..…...............................34
五、p63在其他惡性乳腺瘤之表現………………..…….............................35
六、p63免疫組織化學染色之統計分析結果……………………...............35
第三節 CK14、CK8/18、Vimentin免疫組織化學染色之結果…........................39
一、各抗體於良性混合性乳腺瘤中之表現…………………......................39
二、各抗體於惡性混合性乳腺瘤中之表現…………………......................39
三、免疫組織化學染色分析…………………..............................................49
第四節 Alcian blue與Mucicarmine特殊染色之結果…………….....................50
一、Alcian blue在混合性乳腺腫瘤中之表現……………….......................50
二、Mucicarmine在混合性乳腺腫瘤中之表現…………………................50
第五章 討論……………..........................................................................................52
第六章 總結………………......................................................................................58
參考文獻……………..................................................................................................59

Ellis GL, Auclair PL. Tumors of the salivary glands. Atlas of tumor pathology. 3rd ed. Washington, DC: Armed Forces Institute of Pathology; 1996.
Harvey HJ, Mammary glands. In:Gay S, ed. Current techniques in small animal surgery. 4th ed. Williams & Wilkins Co, Pennsylvania, 579-584, 1998.
Lana SE, Rutteman GR, Withrow SJ. Tumor of the mammary gland. In: Withrow SJ, Vail DM, eds. Small animal clinical oncology 4th ed. Saunders Elseivier Inc., Canada, 619-636, 2007.
Madewell BB, Theilen GH. Tumors of the mammary gland. In: Theilen GH Madewell BR, eds. Veterinary cancer medicine 2nd ed. Lea and Lebiger, Philadelphia, 327-343, 1987.
Misdorp W. Tumors of the mammary gland. In: Meuten DJ ed. Tumor in domestic animal. 4th ed. Blackwell publishing Co., Iowa state press, 575-606, 2002.
Rosen P. Carcinoma with metaplasia. In: Rosen P, ed. Rosen’s Breast Pathology, vol. 1. Philadelphia: Lippincott Williams & Wilkins, 425–435, 2001.
Rutteman GR, Withrow SJ, MacEwen EG. Tumors of the mammary gland. In: Withrow SJ, MacEwen EG, eds. Small animal clinical oncology. 3rd. WB Saunders Co, Philadelphia, 455-477, 2001.
Ahern TE, Brid RC, Church Bird AE et al: Expression of the oncogene c-erb B 2in canine mammary cancers and tumor derived cell lines. Am J Vet Res 57: 693-696, 1996.
Allen SW, Prasse KW, Mahaffey E. Cytologic differentiation of benign from malignant canine mammary tumors. Vet Pathol 23: 649-655, 1986.
Barbareschi M, Pecciarini L, Cangi MG, Macri E, Rizzo A, Viale G, Doglioni C. p63, a p53 homologue, is a selective nuclear marker of myoepithelial cells of the human breast. Am J Surg Pathol 25:1054-1060, 2001.
Batzakis JG, Kraemer B, Sciubba JJ. The pathology of head and neck tumors: the myoepithelial cell and its participation in salivary gland neoplasia, Part 17. Head Neck Sur 5: 222–233, 1983.
Benazzi C, Sarzi G, Galeotti N, Marcato PS. Basement membrane components in mammary tumors of the dog and the cat. J Comp Pathol 109: 241-252, 1993.
Bilal H, Handra-Luca A, Bertrand JC, Fouret PJ. p63 is expressed in basal and yoepithelial cells of human normal and tumor salivary glan tissue. J Histocem Cytochem 51: 133-139, 2003.
Blanpain C, Fuchs E. p63: revving up epithelial stem-cell potential. Nat Cell Biol 9:731-733, 2007.
Bobek LA, Tsai H, Biesbrock AR, Levine MJ. Molecular cloning, sequence, and specificity of expression of the gene encoding the low molecular weight human salivary mucin (MUC7). J Biol Chem 268: 20563–20569, 1993.
Bravo SP, Montes CL, Becerril UL, Sanchez IM. Myoepithelial cells are the main component in pleomorphic adenomas? Med Oral Patol Oral Cir Bucal 12:110-115, 2007.
Candi E, Rufini A, Terrinoni A, Dinsdale D, Ranalli M, Paradisi A, De Laurenzi V, Spagnoli LG, Catani MV, Ramadan S, Knight RA, Melino G. Differential roles of p63 isoforms in epidermal development: selective genetic complementation in p63 null mice. Cell Death Differ 13: 1037-1047, 2006.
Casey HW, Giles RC, Kwapiem RP. Mammary neoplasia in animals. Pathologic aspects and the effect of contraceptive steroid. Recent Res Cancer Res 66: 129-160, 1979.
Chang SC, Chang CC, Chang TJ, Wong ML. Prognostic factors associated with survival two years after surgery in dogs with malignant mammary tumors: 79 cases (1998–2002). J Am Vet Med Assoc 227: 1625-1629, 2005.
Cao, X. pH-dependent conformational change of gastric mucin leads to sol-gel transition. Biophys. J 76: 1250–1258, 1999.
Carraway KL, Ramdauer VP, Haq B, Carethers Carraway CA. Cell signaling through membrane mucins. Bioessays 25:66-71, 2001.
Cebo C. Recombinant human interleukins IL-1, IL-1, IL-4, IL-6, and IL-7 show different and specific calcium-independent carbohydrate-binding properties. J Biol Chem 276: 5685–5691, 2001.
Celli J, Duijf P, Hamel BC. Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome Cell 99:143–53, 1999.
Concannon RW, Spraker TR, Casey HW, Hansel W. Gross and histopathologic effect of medroxyprogesterone on the mammary gland of adult beagle bitches. Fertil Steril 36: 373-387, 1981.
Coyne JD, Dervan PA, Barr L. High-grade carcinomas of the breast showing patterns of mixed ductal and myoepithelial differentiation (including myoepithelial cell-rich carcinoma of the breast). Histopathology 44: 580–584, 2004.
De Laurenzi V, Melino G. Evolution of functions within the p53/p63/p73. Ann N Y Acad Sci 926:90–100, 2000.
Desseyn JL, Guyonnet-Duperat V, Porchet N, Aubert JP, Laine A. Human mucin gene MUC5B, the 10.7-kb large central exon encodes various alternate subdomains resulting in a super-repeat. Structural evidence for a 11p15. 5 gene family. J. Biol. Chem 272: 3168–3178, 1997.
Destexhe E, Lespagnard L, Degeyter M, Jeymann R, Coignoul E. Immunohistochemical identification of myoepithelial and connective tissue cells in canine mammary tumors. Vet Pathol 30: 146-154, 1993.
Deugnier MA, Moiseyeva EP, Thiery JP, Glukhova Gartner F, Geraldes M, Cassali G, Rema A, Schmitt F. DNA measurement and immunohistochemical characterization of epithelial and mesenchymal cells in canine mixed tumours: putative evidence for a common histogenesis. Vet J 158:39–47, 1999.
Deugnier MA, Teuliere J, Faraldo MM, Thiery JP, Glukhova MA. The importance of being a myoepithelial cell. Breast Cancer Res 4: 224-230, 2002.
DiRenzo J, Signoretti S, Nakamura N, Rivera-Gonzalez R, Sellers W, Loda M, Brown M. Growth factor requirements and basal phenotype of an immortalized mammary epithelial cell line. Cancer Res 62: 89-98, 2002.
Donnay I, Rauis J, Wouters-Ballman P, Devleeschouwer n, Leclerq G, Versteengen JP. Receptors for estrogen, progesterone and epidermal growth factors in normal and tumorous canine mammary tissues. J Reprod Fert, Suppl 47: 501-512, 1993.
Dorn CR, Taylor DON, Frye FL, Hibbard HH. Survey of animal neoplasms in Alameda and Contra Countries, California I. Methodology and description of cases. J Natl Cancer Inst 40: 295-305, 1968.
Dutra AP, Granja NVM, Schitt FA. C-erb B-2 expression and nuclear pleomorphism in canine mammary tumors, Braz J Med Biol Res 37:1673-1681, 2004.
Edwards PC, Bhuiya T, Kelsch RD. Assessment of p63 expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and basal cell and canalicular adenomas. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 97:613-619, 2004.
Egenvall A, Bonnett BN, Ohagen P et al: Incidence of and survival after mammary tumors in a population of over 80,000 insured female dogs in Sweden from 1995 to 2002, Prev Vet Med 69: 109-127, 2005.
Escande F, Aubert JP, Porchet N, Buisine MP. Human mucin gene MUC5AC: organization of its 5’-region and central repetitive region. Biochem J 358: 763-772, 2001.
Erlandson RA, Cardon-Cardo D, Huggins PJ. Histogenesis of benign pleomorphic adenoma (mixed tumor) of the major salivary glands. A ultrastructural and immunohistochemical study. Am J Surg Pathol 8: 803–820, 1984.
Espinosa de los Monters A, Milla’N MY, RamMirez GA, Orda’s J,Reymundo C, Martin de las Mulas J. Expression of maspin in mammary gland tumors of the dogs. Vet Pathol 42: 250-257, 2005.
Etreby MF, Graf KJ. Effect of contraceptive steroid on the mammary gland of female dogs and its relevance to human carcinogenicity. Pharm Ther 5: 369-402, 1979.
Frank DW, Kirton KI, Murchison TE, Quinlan WJ, Cokeman ME, Gilbertson TJ, Feenstra ES, Kimball FA. Mammary tumors and serum-hormones in the bitch treated with medroxyprogesterone acetate for four years. Fertil Steril 31: 340-346, 1979.
Forstner JF. Intestinal mucins in health and disease. Digestion 17: 234–263, 1978.
Fowler EH, Wilson GR, Koestner A. Biologic behavior of canine mammary neoplasms based on a histogenetic classification. Vet Pathol 30: 20-27, 1974.
Gama A, Alves A, Gartner F, Schmitt F. p63: A novel myoepithelial cell marker in canine mammary tissue. Vet Pathol 40: 412-420, 2003.
Genelhu CLS, Cardoso SV, Gocci H, Cassali GD. A comparative study between mixed-type tumours from human salivary and canine mammary glands BMC Cancer 218: 1-29, 2007.
Genelhu MCL, Gobbi H, Soares A, Fores de Marques Campos AH, Ribeiro CA, Cassali GD. Immunohistochemical expression of p63 in pleomorphic adenomas and carcinomas ex-pleomorphic adenomas of salivary glands. Oral Oncology 42: 154–160, 2006.
Gilbertson SR, Kurzman ID, Zachrau RE, Hurvitz AI, Black MM. Canine mammary epithelial neoplasms: biologic implications of morphologic characteristics assessed in 232 dogs. Vet Pathol 20: 127-142, 1983.
Giles RC, Kwapiem RP, Giel RG, Casey HW. Mammary nodules in beagle dogs administered investigational contraceptive steroid. J Natl Cancer Inst 60: 1351-1364, 1978.
Gobbi H, Simpson JF, Borowsky A. Metaplastic breast tumors with a dominant fibromatosis-like phenotype have a high risk of local recurrence. Cancer 85:2170-2182, 1999.
Graham JC, O’Keefe DA, Gelberg HB. Immunohistochemical assay for detecting estrogen receptors in canine mammary tumors. Am J Vet Res 60: 627-630, 1999.
Gudjonsson T, Villadsen R, Nielsen HL, Ronnov-Jessen L, Bissell MJ, Petersen OW. Isolation, immortalization, and characterization of a human breast epithelial cell line with stem cell properties. Genes Dev 16: 693-706, 2002.
Gum JR Jr, Hicks JW, Toribara NW, Siddiki B, Kim YS. Molecular cloning of human intestinal mucin (MUC2) cDNA. Identification of the amino terminus and overall sequence similarity to prepro-von Willebrand factor. J Biol Chem 269: 2440–2446, 1994.
Gustafsson BE. The physiological importance of the colonic microflora. Scand. J Gastroenterol. Suppl 77: 117–131, 1982.
Gusterson BA, Warburton MJ, Mitchell D, Ellison M, Neville AM, Rusland PS. Distribution of myoepithelial cells and basement membrane proteins in the normal breast and in benign and malignant breast diseases. Cancer Res 42: 4763-4770, 1982.
Hagiwara K, McMenamin MG, Miura K, Harris CC. Mutational analysis of the p primers. Cancer Res 59: 4165–4169, 1999.
Hellmen E, Lindgren A, Linell F, Mattson P, Nilsson A. Comparison of histology and clinical variable to DNA ploidy in canine mammary tumors. Vet Pathol 25: 219-226, 1988.
Hellmen E, Bergstrom R, Holmberg L, Spangberg UB, Hannson K, Lindgren A. Prognostic factors in canine mammary tumors: A multivariate study of 202 consecutive cases. Vet Pathol 30: 20-27, 1993.
Hellman E. Characterization of four in vitro established canine mammary carcinoma and one atypical benign mixed tumor cell line. In Vitro Cell Devel Biol 28A:309-319, 1992.
Hellman E. Canine mammart tumor cell lines established in vitro. J Reprod Fert, Suppl 47:489-499, 1993.
Hiraga Y. Immunoreactive MUC1 expression at the deepest invasive portion correlates with prognosis of colorectal cancer. Oncology 55: 307–319, 1998.
Hollingsworth MA, Swanson BJ. Mucin in cancer: Protection and control of the cell. Nature 4: 45-60, 2004.
Hsu WL, Huang HM, Liao JW, Wong ML, Chang SC. Increased survival in dogs with malignant mammary tumours overexpressing HER-2 protein and detection of a silent single nucleotide polymorphism in the canine HER-2 gene. Vet J doi:10.1016/j.tvjl.2007.
Kaelin WGJ. The emerging p53 gene family. J Natl Cancer Inst 91:594–598, 1999.
Little NA, Jochemsen AG. p63. Int J Biochem Cell Biol 34:6–9, 2002.
Kaghad M, Bonnet H, Yang A. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell 90:809–819, 1977.
Karayannopoulou M, Kaldrymidou E, Constantinidis TC. Histological grading and prgnosis in dogs with mammary carcinomas: application of a human grading method. J Comp Pathol 133:1-7, 2005.
Kashiwagi, H. DF3 expression in human gallbladder carcinoma: significance for lymphatic invasion. Int. J. Oncol 16: 455–459, 2000.
King KE, Weinberg WC. p63: defining roles in morphogenesis, homeostasis, and neoplasia of the epidermis. Mol Carcinog 46: 716–724, 2007.
Koster MI, Kim S, Mills AA, DeMayo FJ, Roop DR. p63 is the molecular switch for initiation of an epithelial stratification program. Genes Dev 18:126–131, 2004.
Kusafuka K, Yamaguchi A, Kayano T, Takemura T. Immunohistochemical localization of the bone morphogenic protein-6 in salivary pleomorphic adenomas. Pathol Intl 49:1023-1027, 1999.
Kusafuka K, Hiraki Y, Shukunami C, Yamaguchi A, Kayano T, Takemura T. Cartilage-specific matrix protein Chondromodulin-I is associated with chondroid formation in salivary pleomorphic adenomas. Immunohistochemical analysis. Am J Pathol 158:1465-1472, 2001.
Kusafuka K, Nakano K, Hiraki Y, Shukunami C, Nagatsuka H, Nagai N, Takemura T, Sakaguchi Y, Okazaki K, Kusafuka M, Hisha H, Ikehara S. Expression and localization of cartilage-specific matrix protein chondromodulin-I mRNA in salivary pleomorphic adenomas. Virchows Arch. 446:34–40, 2002.
Lacroix-Triki M, Mery E, Voigt JJ, Istier L, Rochaix P. Value of cytokeratin 5/6 immunostaining using D5/16 B4 antibody in the spectrum of proliferative intraepithelial lesions of the breast. A comparative study with 34bE12 antibody. Virchows Arch 442: 548–554, 2003.
Lakhani SR, Chaggar R, Davies S, ones C, Collins N, Odel C, Stratton MR, O’Hare MJ. Genetic alterations in “normal” luminal and myoepithelial cells. J. Pathol 189: 496-503, 1999.
Lee H, Kimelman D. A dominant-negative form of p63 is required for epidermal proliferation in zebrafish. Dev Cell 2: 607–616, 2002.
Li Y, Kufe D. The human DF3/MUC1 carcinomaassociated antigen signals nuclear localization of the catenin p120(ctn). Biochem. Biophy. Res Commun 281: 440–443, 2001.
Luttges J, Feyerabend B, Buchelt T, Pacena M, Kloppel G. The mucin profile of noninvasive and invasive mucinous cystic neoplasms of the pancreas. Am J Surg Pathol 26: 466–471, 2002.
Martin de las Mulas J, Milla’N Y, Dios R. A prospective analysis of immunohistochemically determined estrogen receptor a and progesterone receptor expression and host and tumor factors as predictors of disease-free period in mammary tumors of the dog. Vet Pathol 42: 200-212, 2005.
Mason JT, O’Leary TJ. Effect of formaldehyde fixation on protein secondary structure: a calorimetric and infrared spectroscopic investigation. J Histochem Cytochem 39: 255-239, 1991.
Meo L, Population-based incidence of mammary tumours in some dog breeds. J Reprod Fretil Suppl 57: 439-443, 2001.
Meryem MK, Celina GK. P63 expression in breast cancer. A highly sensitive and specific marker of metaplastic carcinoma. Am J Surg Pathol 28: 1506-1512, 2004.
Millanta F, Calandrella M, Bari G. Comparison of steroid receptor expression in normal, dysplastic, amd neoplastic canine and feline mammary tissues, Res Vet Sci 79: 225-232, 2005.
Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR, Bradley A. p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398:708–713, 1999.
Misdorp W. Canine mammary tumours: Protective effect of late ovariectomy and stimulating effect of progestins. Vet Quarterly 10: 26-33, 1988.
Misdorp W. Progesragens and mammary tumours in dogs and cats. Acta Endocr 125: 27-31, 1991.
Monlux AW, Roszel JF, MacVean DW, Palmer TW. Classification of epithelial mammary tumors in defined population. Vet Pathol 14: 194-217, 1977.
Nakamori S, Ota DM, Cleary KR, Shirotani K, Irimura T. MUC1 mucin expression as a marker of progression and metastasis of human colorectal carcinoma. Gastroenterology 106: 353–361, 1994.
Nitta T, Sugihara K, Tsuyama S, Murata F Immunohistochemical study of MUC1 mucin in premalignant oral lesions and oral squamous cell carcinoma: association with disease progression, mode of invasion, and lymph node metastasis. Cancer 88: 245–254, 2000.
Oberman HA. Metaplastic carcinoma of the breast: a clinicopathologic study of 29 patients. Am J Surg Pathol 11:918–929, 1987.
Pechoux C, Gudjonsson T, Ronnov-Jessen L, Bissell MJ, Petersen OW. Human mammary luminal epithelial cells contain progenitors to myoepithelial cells. Dev. Biol 206: 88-99, 1999.
Pellegrini G, Dellambra E, Golisano O, Martinelli E, Fantozzi I, Bondanza S, Ponzin D, McKeon F, De Luca M. p63 identifies keratinocyte stem cells. Proc Natl Acad Sci 98:3156–3161, 2001.
Petersen OW, Nielsen HL, Gudjonsson T, Villadsen R, Ronnov- Jessen L, Bissell MJ . The plasticity of human brest carcinoma cells is more than epithelial to mesenchymal conversion. Breast Cancer Res 3: 213-217, 2001.
Pulley LT. Ultrastructural and histochemical demonstration of myoepithelium in mixed tumors of the canine mammary gland. Amer J Vet Res 34: 1513-1522, 1973.
Queiroga FL, Perez-Alenza MD, Silvan G. Role of steroid hormones and prolactin in canine mammary cancers, J Steroid Biochen Mol Biol 94: 181-187, 2005.
Quintarelli G, Scott JE, Dellovo M. The chemical and histochemical properties if alcian blue. Histochemie 4: 99-112, 1964.
Raju GC, Wee A. Spindle cell carcinoma of the breast. Histopathology 16:497–499, 1999.
Ramalho LNZ, Riebeiro-Silva A, Cassali GD, Zucoloto S. The Expression of p63 and Cytokeratin 5 in Mixed Tumors of the Canine Mammary Gland Provides New Insights into the Histogenesis of These Neoplasms. Vet Pathol 43: 424-429, 2006.
Reader JR. Interleukin-9 induces mucus cell metaplasia independent of inflammation. Am. J. Respir. Cell Mol Biol 28: 664–672, 2003.
Ren J, Li Y, Kufe D. Protein kinase C δ regulates function of the DF3/MUC1 carcinoma antigen in β-catenin signaling. J Biol Chem 277: 17616–17622, 2002.
Ribeiro-Silva A, Ramalho LNZ,Garcia SB, Branda˜o DF, Chahud F, Zucoloto S. p63 correlates with both BRCA1 and cytokeratin 5 in invasive breast carcinomas: further evidence for the pathogenesis of the basal phenotype of breast cancer. Histopathology 47: 458–466, 2005.
Rungsipipat A, Tateyama S, Yamaguchi R. Immunohistochemistry analysis of c-yes and c-erb B-2 oncogene products and p53 tumor suppressor protein in canine mammary tumors, J Vet Med Sci 61: 27-32, 1999.
Rutteman GR, Cornelisse CJ, Dijkshoorn NJ, Poortman J, Misdorp W. Flow cytometric analysis of DNA ploidy in canine mammary tumors. Cancer Res 48: 3411-3417, 1988.
Rutteman GR, Misdorp W. Hormonal background of canine and feline mammary tumours. J Reprod Fert, Suppl. 47: 483-487, 1993
Sapino A, Papotti M, Sanfilippo B. Tumor types derived from epithelial and myoepithelial cell lines of R3230AC rat mammary carcinoma. Cancer Res 52: 1553–1560, 1992.
Schofeild BH, Williams BR, Doty SB. Alcian Blue staining of cartilage for electron microscopy. Application of the critical electrolyte concentration principle. Histochemical J 7: 139-149, 1975.
Selman PJ, Mol JA, Rutteman GR, Van Garderen E, Rijnberk A. Progestin-induced growth hormone excess in the dog originates in the mammary gland. Endocrinology 134: 287-292, 1994.
Seifert G, Sobin LH. WHO International classification of tumors. Histological Typing of Salivary Gland Tumors. 2nd ed. Berlin Heidelberg. Spring-Verlag, 1991.
Signoretti S, Waltregny D, Dilks J, Isaac B, Lin D, Garraway L, Yang A, Montironi R, McKeon F, Loda M. p63 is a prostate basal cell marker and is required for prostate development. Am J Pathol 157:1764–1775, 2000.
Song KS. Interleukin-1,and tumor necrosis factor induce MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinases- MSK1-CREB activation in human airway epithelial cells. J Biol Chem 278: 23243–23450, 2003.
Sonnenschein EG, Glickman LT, Goldschmidt MH, McKee LJ. Body conformation, diet and risk of breast cancer in pet dogs: A case-control study. Amer J Epidemiol 133: 694-702, 1991.
Spicer AP, Rowse G J, Lidner TK, Gendler SJ. Delayed mammary tumor progression in Muc-1 null mice. J Biol Chem 270: 30093–30101, 1995.
Stefanou D, Batistatou A, Arkoumani ANE, Agnantis NJ. p63 expression in benign and malignant breast lesions. Histo Histopathol 19:465-471, 2004.
Sugiura T, Matsuyama S, Akiyosi H, Tekenaka S, Yamate J, Kuwamura M, Aoki M, Shimada T, Ohashi F, Kubo K. Expression pattern of the BRCA1 splicing variants in canine normal tissues and mammary gland tumors. J Vet Med Sci 69: 587-592, 2007.
Tateyama S, Cotchin E. Alkaline phosphotase reaction of canine mammary mixed tumors: A light amd electronmicroscopic study. Res Vet Sci 23: 356-364, 1977.
Tateyama S, Cotchin E: Electron microscopic observations on canine mixed mammary tumours, with special reference to cytoplasmic filamentous components. Am J Vet Res 39:1494–1501, 1978.
Tateyama S, Uchida K, Hidaka T, Hirao M, Yamaguchi R. Expression of bone morphogenetic protein-6 (BMP-6) in myoepithelial cells in canine mammary gland tumors. Vet Pathol 38: 703-709, 2001.
Teixeira MR, Qvist H, Bohler PJ. Cytogenetic analysis shows that carcinosarcomas of the breast are of monoclonal origin. Genes Chromosomes Cancer 22:145–151, 1998.
Thompson L, Chang B, Barsky SH. Monoclonal origins of malignant mixed tumors (carcinosarcomas): evidence for a divergent histogenesis. Am J Surg Pathol 20: 277–285, 1996.
Toribara NW. The carboxyl-terminal sequence of the human secretory mucin, MUC6. Analysis of the primary amino acid sequence. J Biol. Chem 272:16398–16403, 1997.
Tse GMK, Tan PH, Lui PCW, Gilks CB, Poon CS, Ma TKF, Law BKB, Larn WWM. The role of immunohistochemistry for smooth-muscle actin, p63, CD10 and cytokeratin 14 in the differential diagnosis of papillary lesions of the breast. J. Clin. Pathol 60:315-320, 2007.
Van Bokhoven H, Brunner HG. Splitting p63. Am J Hum Genet 71:1–13, 2002.
Van Leeuwen IS, Hellmen E, Cornelisse CJ, Van der Burg B, Rutteman GR. P53 mutations in mammary tumor cell lines and corresponding tumor tissues in the dog. Anticancer Res 16: 3737-3743, 1996.
Velcich, A. Colorectal cancer in mice genetically deficient in the mucin Muc2. Science 295: 1726–1729, 2002.
Vos JH, Van den Ingh TS, Misdorp W, Molenbeek RF, Van Mil FN, Rutteman GR, Lvany D, Ramaekers FCS: Immunohistochemistry with keratin, vimentin, desmin, and α-smooth muscle actin monoclonal antibodies in canine mammary gland: benign mammary tumors and duct ectasias. Vet Q 14: 89–95, 1993.
Wada H, Enomoto T, Tsujimoto M. Carcinosarcoma of the breast: molecular-biological study for analysis of histogenesis. Hum Pathol 29:1324–1328, 1998.
Wargotz ES, Deos PH, Norris HJ. Metaplastic carcinomas of the breast: II. Spindle cell carcinoma. Hum Pathol 20: 732–740,1989.
Wen Y, Caffrey TC, Wheelock M J, Johnson KR, Hollingsworth MA. Nuclear association of the cytoplasmic tail of muc1 and β-catenin. J Biol Chem 278: 38029–38039, 2003.
Yamaguchi K, Wu L, Caballero OL. Frequent gain of the p40/p51/p63 gene locus in primary head and neck squamous cell carcinoma. Int J Cancer 86:684–689, 2002.
Yamagami T, Kobayashi T, Takahashi K, Sugiyama M. Prognosis for canine malignant mammary tumors based on TNM and histologic classification. J Vet Med Sci 58: 1079-1083, 1996.
Yang A, Kaghad M, Wang Y. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell 2:305–316, 1998.
Yang A, Schweitzer R, Sun D. p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398:714–718, 1999.
Yang A, Mc Keon F. p63 and p73: p53 mimics, menaces and more. Nat Rev Mol Cell Biol 1:194–207, 2000.
Yuzbasiyan-Gurkan V, Cao Y, Venta P, Yamini B. Loss of heterogenozygosity at the BRCA1 locus in canine mammary carcinoma. Proc Vet Cancer Soc 19: 7, 1999.
Zarbo RJ, Prasad AR, Regezi JA, Gown AM, Savera AT. Salivary gland basal cell and canalicular adenomas: immunohistochemical demonstration of myoepithelial cell participation and morphogenetic considerations. Arch Pathol Lab Med 124: 401-405, 2000.
Zhuang Z, Lininger RA, Man YG. Identical clonality of both components of mammary carcinosarcoma with different loss of heterozygosity. Mod Pathol 10: 354–362, 1997.