Skip to main content
Top
Published in: BMC Cancer 1/2007

Open Access 01-12-2007 | Research article

Proto-oncogene HER-2 in normal, dysplastic and tumorous feline mammary glands: an immunohistochemical and chromogenic in situ hybridization study

Authors: Javier Ordás, Yolanda Millán, Rafaela Dios, Carlos Reymundo, Juana Martín de las Mulas

Published in: BMC Cancer | Issue 1/2007

Login to get access

Abstract

Background

Feline mammary carcinoma has been proposed as a natural model of highly aggressive, hormone-independent human breast cancer. To further explore the utility of the model by adding new similarities between the two diseases, we have analyzed the oncogene HER-2 status at both the protein and the gene levels.

Methods

Formalin-fixed, paraffin-embedded tissue samples from 30 invasive carcinomas, 7 benign lesions and two normal mammary glands were analyzed. Tumour features with prognostic value were recorded. The expression of protein HER-2 was analyzed by immunohistochemistry and the number of gene copies by means of DNA chromogenic in situ hybridization.

Results

Immunohistochemical HER-2 protein overexpression was found in 40% of feline mammary carcinomas, a percentage higher to that observed in human breast carcinoma. As in women, feline tumours with HER-2 protein overexpression had pathological features of high malignancy. However, amplification of HER-2 was detected in 16% of carcinomas with protein overexpression, a percentage much lower than that observed in their human counterpart.

Conclusion

Feline mammary carcinoma would be a suitable natural model of that subset of human breast carcinomas with HER-2 protein overexpression without gene amplification.
Appendix
Available only for authorised users
Literature
1.
go back to reference Siegel PM, Dankort DL, Hardy WR, Muller WJ: Novel activating mutations in the neu proto – oncogene involved in induction of mammary tumors. Mol Cell Biol. 1994, 14: 7068-7077.CrossRefPubMedPubMedCentral Siegel PM, Dankort DL, Hardy WR, Muller WJ: Novel activating mutations in the neu proto – oncogene involved in induction of mammary tumors. Mol Cell Biol. 1994, 14: 7068-7077.CrossRefPubMedPubMedCentral
2.
go back to reference Sahin AA: Biologic and clinical significance of HER-2/neu (cerbB-2) in breast cancer. Adv Anat Pathol. 2000, 7: 158-166.CrossRefPubMed Sahin AA: Biologic and clinical significance of HER-2/neu (cerbB-2) in breast cancer. Adv Anat Pathol. 2000, 7: 158-166.CrossRefPubMed
3.
go back to reference Ross JS, Fletcher JA, Bloom KJ, Linnette GP, Stec J, Symmans WF, Pusztai L, Hortobagyi GN: Targeted therapy in breast cancer: the HER-2/neu gene and protein. Mol Cell Proteomics. 2004, 3: 379-398. 10.1074/mcp.R400001-MCP200.CrossRefPubMed Ross JS, Fletcher JA, Bloom KJ, Linnette GP, Stec J, Symmans WF, Pusztai L, Hortobagyi GN: Targeted therapy in breast cancer: the HER-2/neu gene and protein. Mol Cell Proteomics. 2004, 3: 379-398. 10.1074/mcp.R400001-MCP200.CrossRefPubMed
4.
go back to reference Tanner M, Gancberg D, Di Leo A, Larsimont D, Rouas G, Paccart MJ, Isola J: Chromogenic in Situ Hybridization. A practical alternative for fluorescence in Situ Hybridization to detect HER-2/neu oncogene amplification in Archival Breast Cancer Samples. Am J Pathol. 2000, 157: 1467-1472.CrossRefPubMedPubMedCentral Tanner M, Gancberg D, Di Leo A, Larsimont D, Rouas G, Paccart MJ, Isola J: Chromogenic in Situ Hybridization. A practical alternative for fluorescence in Situ Hybridization to detect HER-2/neu oncogene amplification in Archival Breast Cancer Samples. Am J Pathol. 2000, 157: 1467-1472.CrossRefPubMedPubMedCentral
5.
go back to reference Isola J, Tanner M, Forsyth A, Cooke TG, Watters AD, Bartlett JMS: Interlaboratory comparison of HER-2 oncogene amplification by chromogenic and fluorescence in situ hybridization. Clin Cancer Res. 2004, 10: 4793-4798. 10.1158/1078-0432.CCR-0428-03.CrossRefPubMed Isola J, Tanner M, Forsyth A, Cooke TG, Watters AD, Bartlett JMS: Interlaboratory comparison of HER-2 oncogene amplification by chromogenic and fluorescence in situ hybridization. Clin Cancer Res. 2004, 10: 4793-4798. 10.1158/1078-0432.CCR-0428-03.CrossRefPubMed
7.
go back to reference Frese K: Comparative pathology of mammary tumors of domestic animals. Pathology of Neoplastic and Endocrine induced diseases of the breast. Edited by: Bäsler R, Hübner K. 1986, Stuttgart: Gustav Fischer Verlag, 44-61. Frese K: Comparative pathology of mammary tumors of domestic animals. Pathology of Neoplastic and Endocrine induced diseases of the breast. Edited by: Bäsler R, Hübner K. 1986, Stuttgart: Gustav Fischer Verlag, 44-61.
8.
go back to reference Rutteman GR, Withrow SJ, MacEwen EG: Tumors of the mammary gland. Small Animal Clinical Oncology. Edited by: Withrow SJ, MacEwen BR. 2001, Philadelphia: W.B. Saunders Company, 455-477. Rutteman GR, Withrow SJ, MacEwen EG: Tumors of the mammary gland. Small Animal Clinical Oncology. Edited by: Withrow SJ, MacEwen BR. 2001, Philadelphia: W.B. Saunders Company, 455-477.
9.
go back to reference Millanta F, Calandrella M, Citi S, Della Santa D, Poli A: Overexpression of HER-2 in feline invasive mammary carcinomas: An immunohistochemical survey and evaluation of its prognostic potential. Vet Pathol. 2005, 42: 30-34. 10.1354/vp.42-1-30.CrossRefPubMed Millanta F, Calandrella M, Citi S, Della Santa D, Poli A: Overexpression of HER-2 in feline invasive mammary carcinomas: An immunohistochemical survey and evaluation of its prognostic potential. Vet Pathol. 2005, 42: 30-34. 10.1354/vp.42-1-30.CrossRefPubMed
10.
go back to reference Winston J, Craft DM, Scase TJ, Bergman PJ: Immunohistochemical detection of HER-2/nu expression in spontaneous feline mammary tumours. VCO. 2005, 3: 8-15. Winston J, Craft DM, Scase TJ, Bergman PJ: Immunohistochemical detection of HER-2/nu expression in spontaneous feline mammary tumours. VCO. 2005, 3: 8-15.
11.
go back to reference De Maria R, Olivero M, Iussich S, Nakaichi M, Murata T, Biolatti B, Di Renzo F: Spontaneous feline mammary carcinoma is a model of HER2 overexpressing poor prognosis human breast cancer. Cancer Res. 2005, 65: 907-912.PubMed De Maria R, Olivero M, Iussich S, Nakaichi M, Murata T, Biolatti B, Di Renzo F: Spontaneous feline mammary carcinoma is a model of HER2 overexpressing poor prognosis human breast cancer. Cancer Res. 2005, 65: 907-912.PubMed
12.
go back to reference Ahern TE, Bird RC, Bird AE, Wolfe LG: Expression of the oncogene c-erbB-2 in canine mammary cancers and tumor-derived cell lines. Am J Vet Res. 1996, 57: 693-696.PubMed Ahern TE, Bird RC, Bird AE, Wolfe LG: Expression of the oncogene c-erbB-2 in canine mammary cancers and tumor-derived cell lines. Am J Vet Res. 1996, 57: 693-696.PubMed
13.
go back to reference Rungsipipat A, Tateyama S, Yamaguchi R, Uchida K, Miyoshi N, Hayashi T: Immunohistochemical analysis of c-yes and c-erbB-2 oncogene products and p53 tumor suppressor protein in canine mammary tumors. J Vet Med Sci. 1999, 61: 27-32. 10.1292/jvms.61.27.CrossRefPubMed Rungsipipat A, Tateyama S, Yamaguchi R, Uchida K, Miyoshi N, Hayashi T: Immunohistochemical analysis of c-yes and c-erbB-2 oncogene products and p53 tumor suppressor protein in canine mammary tumors. J Vet Med Sci. 1999, 61: 27-32. 10.1292/jvms.61.27.CrossRefPubMed
14.
go back to reference Martín de las Mulas J, Ordás J, Millán Y, Fernández-Soria V, Ramón y, Cajal S: Oncogene HER-2 in canine mammary gland carcinomas: An immunohistochemical and chromogenic in situ hybridization study. Breast. 2003, 80: 363-367. Martín de las Mulas J, Ordás J, Millán Y, Fernández-Soria V, Ramón y, Cajal S: Oncogene HER-2 in canine mammary gland carcinomas: An immunohistochemical and chromogenic in situ hybridization study. Breast. 2003, 80: 363-367.
15.
go back to reference Dutra AP, Granja NV, Schmitt FC, Cassali GD: c-erbB-2 expression and nuclear pleomorphism in canine mammary tumors. Braz J Med Biol Res. 2005, 37: 1673-1681. Dutra AP, Granja NV, Schmitt FC, Cassali GD: c-erbB-2 expression and nuclear pleomorphism in canine mammary tumors. Braz J Med Biol Res. 2005, 37: 1673-1681.
16.
go back to reference Kott C, Matz-Rensing K, Kaup FJ: Hercep test applied in mammary tumors in female dogs. Kleintierpraxis. 2005, 50: 221-227. Kott C, Matz-Rensing K, Kaup FJ: Hercep test applied in mammary tumors in female dogs. Kleintierpraxis. 2005, 50: 221-227.
17.
go back to reference Misdorp W, Else RW, Hellmen E, Lipscomb TP: Histological classification of the mammary tumors of the dog and the cat. Second series. 1999, Washington, DC: AFIP, VII: Misdorp W, Else RW, Hellmen E, Lipscomb TP: Histological classification of the mammary tumors of the dog and the cat. Second series. 1999, Washington, DC: AFIP, VII:
18.
go back to reference Castagnaro M, Casalone C, Ru G, Nervi GC, Bozzeta E, Caramelli M: Tumour grading and the one-year post-surgical prognosis in feline mammary carcinomas. J Comp Pathol. 1998, 119: 263-275. 10.1016/S0021-9975(98)80049-2.CrossRefPubMed Castagnaro M, Casalone C, Ru G, Nervi GC, Bozzeta E, Caramelli M: Tumour grading and the one-year post-surgical prognosis in feline mammary carcinomas. J Comp Pathol. 1998, 119: 263-275. 10.1016/S0021-9975(98)80049-2.CrossRefPubMed
19.
go back to reference Martín de las Mulas J, van Niel M, Millán Y, Blakenstein MA, van Mil F, Misdorp W: Immunohistochemical analysis of estrogen receptors in feline mammary gland benign and malignant lesions: comparison with biochemical assay. Domes Anim Endocrinol. 2000, 18: 111-125. 10.1016/S0739-7240(99)00067-3.CrossRef Martín de las Mulas J, van Niel M, Millán Y, Blakenstein MA, van Mil F, Misdorp W: Immunohistochemical analysis of estrogen receptors in feline mammary gland benign and malignant lesions: comparison with biochemical assay. Domes Anim Endocrinol. 2000, 18: 111-125. 10.1016/S0739-7240(99)00067-3.CrossRef
20.
go back to reference Martín de las Mulas J, van Niel M, Millán Y, Blankenstein MA, Van Mil F, Misdorp W: Progesterone receptors in normal, dysplastic and tumorous feline mammary glands. Comparison with oestrogen receptors status. Res Vet Sci. 2002, 72: 153-161. 10.1053/rvsc.2001.0542.CrossRefPubMed Martín de las Mulas J, van Niel M, Millán Y, Blankenstein MA, Van Mil F, Misdorp W: Progesterone receptors in normal, dysplastic and tumorous feline mammary glands. Comparison with oestrogen receptors status. Res Vet Sci. 2002, 72: 153-161. 10.1053/rvsc.2001.0542.CrossRefPubMed
21.
go back to reference Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987, 235: 177-182. 10.1126/science.3798106.CrossRefPubMed Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987, 235: 177-182. 10.1126/science.3798106.CrossRefPubMed
Metadata
Title
Proto-oncogene HER-2 in normal, dysplastic and tumorous feline mammary glands: an immunohistochemical and chromogenic in situ hybridization study
Authors
Javier Ordás
Yolanda Millán
Rafaela Dios
Carlos Reymundo
Juana Martín de las Mulas
Publication date
01-12-2007
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2007
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-7-179

Other articles of this Issue 1/2007

BMC Cancer 1/2007 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine