Amplification of the c-yes oncogene in canine mammary tumors

Genomic DNAs of 14 mammary tumors were analyzed by Southern blot hybridization using a human c-yes-1 oncogene probe. The amplification was successful in half of the cases (7 adenocarcinomas). The degree of amplification was approximately 4-fold, and a high proportion was seen in malignant tumors. In addition, DNA polymorphism was detected in two adenocarcinomas.     

The expression of sialyl Lewis X in canine and feline mammary gland tumors

The expression of sialyl Lewis X (sLe(x)) in 93 canine and 15 feline mammary gland tumors (MGT) obtained by surgical resection at Veterinary Medical Center, the University of Tokyo was examined by immunohistochemistry. Their clinicopathological features and prognosis were also reviewed. Approximately 60% of MGT tissues showed sLe(x) positive expressions, while all normal mammary gland tissues were negative. However, its expression was not correlated with clinicopathological features and prognosis significantly. This study suggests that sLe(x) may be a tumor-associated antigen in canine and feline MGTs.     

Amyloid in canine mammary tumors

In canine mammary carcinomas, amyloid was present as amyloid-containing corpora amylacea and as local deposits between neoplastic epithelial cells or in stromal tissue. Histochemical staining methods revealed that this amyloid was not of the AA-type amyloid and contained tryptophan. The possible pathogenesis of this amyloid deposition is discussed.     

Expression levels of the focal adhesion-associated proteins paxillin and p130CAS in canine and feline mammary tumors

Paxillin and p130CAS are two adaptor proteins localized at the focal adhesions which play an important role in cell signaling, cell motility and oncogenic transformation. In this study we evaluated the levels of paxillin and p130CAS in feline and canine mammary tumor tissues at different stages of malignancy. The results obtained by Western blotting analysis showed no significant differences in the amounts of paxillin and p130CAS between normal and non-invasive tumor tissues. By contrast, mammary tumor tissues with the invasive phenotype showed lower levels of paxillin P < 0.01 and higher levels of p130CAS P < 0.001 than normal tissues. The decrease P < 0.001 of the amount of paxillin and the increase P < 0.001 of p130CAS levels were correlated with the progression stage of malignancy. Since paxillin and p130CAS are involved in regulating cell migration, our results suggest that low levels of paxillin together with high levels of p130CAS expression may cause certain breast cancers to be more motile and possibly more aggressive. Thus, both paxillin and p130CAS may represent useful prognosticators of feline and canine breast cancer malignancy.     

Prognostic factors for feline mammary tumors

The case records of 100 cats with malignant mammary tumors were reviewed. All cats were staged clinically according to the staging system of the World Health Organization. The following information was obtained from the medical records: age at time of diagnosis, breed, tumor size, date of surgery, type of surgical procedure performed, histologic type of tumor, disease-free interval, survival time, and cause of death. Factors of no prognostic value were age (less than or equal to 10 years vs greater than 10 years) and breed. Tumor size was the most significant prognostic factor (P less than 0.0001). Cats with small tumors (1 cm3 to 8 cm3) had the best prognosis. The type of surgery, conservative vs radical, was significantly (P less than 0.01) related to disease-free interval, but was of no significance in prolonging survival time.     

Localized amyloidosis in canine mammary tumors

Histopathologic and immunohistochemical examinations were performed on localized amyloidosis associated with mammary tumors in two dogs. These tumors were identified as adenoma and adenocarcinoma. An acellular, amorphous pale eosinophilic material (amyloid) was observed in the lumina of acini lined by neoplastic cells and in the stroma of the tumors. Concentrically laminated pale eosinophilic bodies (corpora amylacea) were also found in the lumina of the acini. Amyloid and corpora amylacea stained positively with Congo red with and without 5% potassium permanganate pretreatment and revealed a green birefringence under polarized light. Corpora amylacea showed an occasional Maltese-cross pattern. Immunohistochemically, amyloid and corpora amylacea usually stained positively with anti-bovine alpha-casein antibody but negatively with anti-human amyloid AA, anti-bovine kappa-light and lambda-light chains, anti-human lactoferrin, anti-human transferrin, anti-human secretory component, and anti-human polyglucosan antibodies. These findings suggested that the amyloid deposition in these canine mammary tumors was related to lactating casein.     

Classification and grading of canine mammary tumors

Mammary neoplasms are the most common neoplasm in female dogs. Two histologic classification systems for canine mammary tumors and dysplasias have been published: the first in 1974 and a modification in 1999. This article provides a brief overview of the two histologic classification systems. Since the publication of the second system, several new histologic subtypes of canine mammary neoplasms have been described. These have been incorporated into the proposed new classification system. This article also compares the grading systems for canine mammary carcinomas and their use for prognosis, along with the histologic classification.     

E-cadherin immunoreactivity in canine mammary tumors.

The reduction or loss of E-cadherin (E-cad), a calcium-dependent epithelial cell adhesion molecule, has been associated with tumor dedifferentiation and invasiveness. The immunohistochemical pattern of E-cad expression was evaluated in formalin-fixed and paraffin-embedded sections of 6 normal mammary glands, 3 dysplasias, 12 benign tumors (8 benign mixed tumors, 4 adenomas), and 60 malignant tumors (12 stage 0, 29 stage I, 19 stage II) of the canine mammary gland. E-cadherin expression was classified as membranous, when on cell-cell boundaries, or as cytoplasmic, when in the form of a diffuse cytoplasmic staining. In addition, the percentage of E-cad-positive epithelial neoplastic cells was graded by a semiquantitative method, categorizing cases into a reduced (or -) type group, when showing less than 25% positivity, a reduced (or +/-) type group, when showing 25-75% positivity, and a preserved (or +) type group, when more than 75% positive cells were present. In the normal mammary gland, E-cad expression was evident in epithelial luminal cells. A stronger positivity was revealed in ductular than in alveolar luminal cells. The myoepithelial cells showed inconsistent, weak cytoplasmic positivity in the normal gland as well as in mammary tumors. In normal glands and benign and malignant noninvasive tumors, E-cad expression was mainly membranous and preserved in most of the epithelial cells. In stage I tumors, both membranous (38%) and cytoplasmic (62%) positivity were well represented, as well as preserved type (55%) and reduced type (45%) tumors. All stage II malignant tumors showed the highest frequency of cytoplasmic positivity (79%) and reduced type (62%) tumors.     

Cyclooxygenase-2 expression in canine mammary tumors

Mammary tumors are the most common neoplasms in female dogs. Induction of cyclooxygenase-2 (COX-2) has been implicated in various cancers in humans. However, expression of COX-2 has not been investigated in canine mammary tumors. Normal mammary gland (n = 4), simple or complex adenomas (n = 63), and simple or complex adenocarcinomas (n = 84) were studied by immunohistochemistry. Results showed that COX-2 was not expressed in the normal gland but was detected in 24% of adenomas and in 56% of adenocarcinomas (P < 0.001). The incidence of COX-2 expression and the intensity of the COX-2 signal were higher in adenocarcinomas than in adenomas (P < 0.001). These results demonstrate for the first time that COX-2 is induced in a proportion of canine mammary tumors and that COX-2 expression is more frequent and more intense in malignant than in benign tumors, suggesting a potential role for COX-2 in canine mammary tumorigenesis.     

Microsatellite instability in canine mammary gland tumors

BACKGROUND: Genomic instability is a hallmark of cancer and may be required for the accumulation of cancer-causing mutations within cells. One form of genomic instability occurs in tandem nucleotide repeats and is known as microsatellite instability (MSI). HYPOTHESIS: We hypothesized that MSI can be observed in canine mammary gland tumors (MGT) and represents a potential carcinogenic mechanism in dogs. ANIMALS: Thirty-five dogs with MGTs and 9 dogs with other tumors were recruited from the University of Minnesota Veterinary Medical Center and referring veterinary clinics. METHODS: A panel of 21 canine microsatellite (MS) markers was amplified by polymerase chain reaction (PCR) from deoxyribonucleic acid obtained from blood and from fresh or formalin-fixed, paraffin-embedded tumor tissues. PCR products were evaluated by using capillary electrophoresis, and the chromatograms were analyzed by using genotyping software. MS genotypes obtained from fresh and formalin-fixed tumor tissues were compared, as were MS genotypes from normal tissue and tumor tissue. RESULTS: Genotypes obtained from formalin-fixed and fresh tissues were identical for all MS in 9 tumors evaluated, suggesting excellent concordance between the 2 sample types. For the 35 canine mammary tumors evaluated, 13 (37%) had stable genotypes; 22 (63%) exhibited aberrations in 1 or 2 MS; and 4 tumors (11%) demonstrated high-level instability, with aberrations in 29 to 61% of MS. CONCLUSIONS AND CLINICAL IMPORTANCE: Although some low-level MSI often is observed, high-level MSI is an infrequent finding in canine mammary tumors. Further evaluations are required to better characterize this phenomenon and to determine its relevance to canine carcinogenesis.     

Determination of estrogen receptors in canine mammary tumors

Dextran-coated charcoal assay with Scatchard plotting was used for the quantitative determination of high-affinity estradiol receptors (ER) in 10 canine mammary tumor cytosols. Mammary tumors diagnosed histopathologically as adenocarcinomas appeared to have a higher incidence of ER than those diagnosed as mixed mammary tumors. These receptors have a high affinity for estradiol with dissociation constants as determined by Scatchard analysis ranging from 1.2 to 2.0 X 10(-11) M. These dissociation constants are similar to those previously reported for the receptor-estradio interaction from target tissues in other species. The specific binding of the receptor for the hormone was diminished in the presence of an antiestrogenic compound. Our data suggest that canine mammary tumors with significant ER levels would respond favorably to antiestrogen therapy. With the demonstration of ER sites in canine mammary adenocarcinomas as presented herein, the potential for chemotherapeutic management appears to be encouraging.     

Frequency of canine and feline tumors in a defined population.

The Tulsa Registry of Canine and Feline Neoplasms was the second animal tumor registry in the United States concerned with a defined population in a delimited geographic area. Only tumors histologically confirmed by registry pathologists were included in frequency statistics based on the annual dog and cat population presented to veterinarians. During the first registry year, about 1% of the 63,504 dogs and 0.5% of the 11,909 cats had one or more primary tumors. While the incidence rate for malignant tumors in dogs was similar to that in cats, the incidence of benign tumors of dogs was over 10 times that of cats. The most common tumors were sebaceous adenoma in dogs and lymphosarcoma in cats. Mammary cancer was the most common malignant tumor in dogs. Mammary tumors of female dogs were significantly more frequent in Pointers, Poodles and Boston Terriers, in that order, than in other breeds. A greater incidence of mammary tumors among intact compared to spayed female dogs was seen for virtually every age group except in the Pointer breed.     

Alpha basic crystallin expression in canine mammary tumors

The aim of this study was to evaluate prognostic and/or diagnostic factors of canine mammary tumors by immunohistochemically analyzing the expression of alpha basic crystallin (αB-c). For this, formalin-fixed, paraffin-embedded blocks of 51 naturally-occurring canine mammary tumors (11 benign and 40 malignant) were used. Tissue from eight normal canine mammary glands were served as a control. Immunohistochemically, in the control mammary tissues, a few luminal epithelial cells were αB-c positive but myoepithelial cells were negative. In benign or simple type malignant tumors, αB-c expression was observed in luminal epithelial cells while the myoepithelial basal cells were negative. In benign or complex type malign tumors, positive staining was predominantly found in the cytoplasm of epithelial cells. Immunoreactivity of αB-c was also observed in neoplastic myoepithelial cells. Statistically, the number of cells immunolabeled with αB-c was found to be significantly different among tissues from normal canine mammary glands, benign lesions, and malignant tumors (p < 0.05). αB-c immunoreactivity was higher in malignant tumors than the control mammary tissues (p < 0.001). Data obtained in the current study revealed a strong association between high expression levels of αB-c and primary mammary gland tumors in canines.     

犬乳腺肿瘤的诊治1例

犬乳腺肿瘤在母犬中非常常见,是仅次于皮肤肿瘤的最常见肿瘤,母犬的发生率约0.2%,大约50%的犬乳腺肿瘤是恶性的.犬后面几个乳腺发生肿瘤的可能性更大,因它们相对大一些,含的细胞略多一些,恶变的可能性也大一些.笔者近日诊断并治疗了一病例,现介绍如下:一.病史与临床检查(一)症状2010年9月21日,安徽省来安县一头12岁雌性(未绝育)京巴犬来我院就诊,体重6.3千克,主诉该犬两年多前左侧最后乳腺能摸到豌豆大硬块,但生长速度不快,最近半年硬块变大,速度较快,约一周前硬块表面皮肤破溃,一直不愈合,最近两天吃食不香.     

Cellular proliferative and telomerase activity in canine mammary gland tumors

In canine mammary tumors, we examined the telomerase activity, proliferative activity by proliferative cell nuclear antigen (PCNA) immunohistochemistry, and percentage of apoptotic cells by the deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. The relationship between these measures and histopathologic malignancy was also investigated. PCNA index was highest in malignant tumors (adenocarcinoma: 27.0%; malignant mixed tumor: 15.7%), followed by benign tumors (adenoma: 4.4%; benign mixed tumor: 5.3%), hyperplasia (2.1%), and normal mammary gland (0.9%). In adenoma and adenocarcinoma, papillary and solid types showing higher cellularity tended to have higher PCNA indices than did cystic and tubular types. Although the TUNEL index was <1% in all cases, the relationship between this measure and histopathologic diagnosis showed the same tendency as observed in PCNA immunostaining. Telomerase activity was detectable in all adenomas, benign mixed tumors, and adenocarcinomas examined. In contrast, all normal mammary glands, hyperplasias, and malignant mixed tumors were negative for telomerase. Relative telomerase activity (RTA) of adenocarcinoma (56.5) was significantly higher than that of adenoma (27.8) and benign mixed tumor (33.9), and a significant positive correlation (P < 0.001) was noted between RTA and PCNA index. No significant correlations were noted between either PCNA or TUNEL index and clinical features such as metastasis and tumor diameter. PCNA index and telomerase activity may be useful markers for judging malignancy of canine mammary tumors.     

Telomere length and telomerase activity in canine mammary gland tumors

OBJECTIVE: To measure telomere length and telomerase activity in naturally occurring canine mammary gland tumors. SAMPLE POPULATION: 27 mammary gland tumor specimens obtained during resection or necropsy and 12 mammary gland tissue specimens obtained from healthy (control) dogs. PROCEDURE: Telomere length in tissue specimens was measured by use of restriction endonuclease digestion and Southern blot analysis. Telomerase activity was measured by use of a telomeric repeat amplification protocol assay. RESULTS: Telomere length in mammary gland tumors ranged from 11.0 to 21.6 kilobase pairs (kbp; mean +/- SEM, 14.5+/-0.5 kbp) but did not differ among tumor types. Telomeres in mammary gland tumors were slightly shorter than in normal tissue specimens, but telomere length could not be directly compared between groups, because mean age of dogs was significantly different between groups. Age was negatively correlated with telomere length in control dogs but was not significantly correlated with length in affected dogs. Telomerase activity was detected in 26 of 27 mammary gland tumors and in 4 of 12 normal tissue specimens. However, telomerase activity and telomere length were not correlated in tumor specimens. CONCLUSIONS AND CLINICAL RELEVANCE: Telomere length is maintained in canine mammary gland tumors regardless of the age of the affected dog. Measurement of telomere length may be a useful tool for monitoring the in vivo effects of telomerase inhibitors in dogs with tumors.     

Prognostic studies of canine and feline mammary tumours: the need for standardized procedures

For several years, veterinary oncologists have been struggling with the prognosis of mammary tumours in dogs and cats. Translation of tumour characteristics into prognostic information is an invaluable tool for the use of the most appropriate therapies, as well as for planning innovative therapeutic trials. Moreover, canine and feline spontaneous mammary gland tumours are good models for the study of human breast cancer. Collecting and interpreting information regarding the prognosis of canine and feline mammary tumours is difficult due to the fact that different methods have been applied to study various components and characteristics. This review identifies some of the challenges of prognostic studies of spontaneous canine and feline mammary tumours and suggests standardized procedures to overcome these challenges and facilitate reproducibility and assessment of results.