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Developing new therapies for feline mammary cancer

Figueira AC, Teodosio AS, Carvalheira J, Lacerda M, de Matos A and Gartner F. P-cadherin expression in feline mammary tissues. Veterinary Medicine International. 2012; 2012. [Free, full text article}

Feline mammary gland tumors are the third most common neoplasia in the domestic cat after skin and lymphohematopoietic tumors, accounting for 17% of all neoplasms in female cats (but rare in male cats). Mammary epithelial tumors are the most common type of feline mammary tumor, with adenocarcinomas (i.e., tubular, papillary, or solid) predominating. Tumors occur at a mean age between 10 to 12 years with Siamese, domestic short-haired, and tri-colored cats having an increased risk. Unfortunately, most cats have advanced disease when first presented to veterinarians, averaging 5 months after the neoplasia is first noticed. Treatment of choice is radical mastectomy of all glands on the affected side or bilateral mastectomy if possible, because of the high local recurrence rate, high rate of metastasis, and the frequent multicentric origin of feline mammary gland tumors. Often surgery for the opposite side is staged 2-4 weeks later. Also, all regional lymph nodes should be palpated and removed if enlarged. Ovariohysterectomy at an early age (< 6 months old) has a significant sparing effect. Significant factors affecting survival include the size, extent of surgery, and histologic grade of the tumor. The overall average time from detection of tumor to death is about 1 year with surgery alone. Due to the high metastatic potential of mammary carcinoma, adjuvant chemotherapy may improve survival times, but additional studies are needed.

Cadherins are cellular adhesion proteins that play an important role in the formation and maintenance of normal tissue architecture. Placental cadherin (P-cadherin) is a classical cadherin expressed by myoepithelial cells of the mammary gland. Changes in P-cadherin expression in mammary tissue have been implicated in human mammary carcinogenesis. Feline mammary tumors have similar histological and clinical course as human breast cancer; therefore, similar changes in aberrant P-cadherin expression are expected in cats. The present study included histological examination and P-cadherin immunolabelling chemistry of mammary tissue from cats with normal (n=4), hyperplastic (n=12), benign (n=6), and various malignancies (n=39). P-cadherin was aberrantly expressed only in mammary epithelial cells in malignant tumors as similarly observed in human breast cancer. Degree of expression was also positively correlated with histological grade.

Abnormal expression of P-cadherin may provide a promising antibody therapeutic target for humans and cats with mammary neoplasia, in particular in cases with metastatic disease. Disease conditions similar in humans and cats, such as mammary neoplasia, provide an excellent example of the “one world, one health, one medicine” paradigm. [GO]

See also: Hughes K and Dobson JM. Prognostic histopathological and molecular markers in feline mammary neoplasia. Vet J. 2012; 194: 19-26.