| Summary: | 碩士 === 國立臺灣大學 === 獸醫學研究所 === 91 === Canine mammary gland tumors (MGTs) are the most frequent neoplasm in bitches. The etiology of mammary tumors in dog is multifactorial involvement and hormones dependent. The hormone factor is considered the most important factor in the development of mammary tumors. In addition, a balance between proliferation, differentiation, and death of the cells is critical for normal development and homeostasis of the mammary gland. Loss of balance may allow accumulation of mutations that result in MGT. Therefore, the aim of this study is to analyze and correlate the expression of estrogen receptor and Bcl-2 protein, proliferative activity and apoptosis in canine MGTs. Thirty-three female dogs with 39 surgically excised MGT specimens from Department of Surgery, National Taiwan University Veterinary Hospital (NTUVH) were collected for basic information analysis, immunohistochemistry (IHC) of ER, Bcl-2 protein, Ki67 antigen, and TUNEL assay. The mean age of MGT affected dogs was 10.4 years old. Mixed species (17/33; 51.5%) was the most common breed in this study, the next was Maltese (6/33; 18.2%). 69.7% (22/33) of canine MGTs occurred in gland 4 and 5. The ratio of benign and malignant tumors was 4: 6. The results of IHC showed 79.5% (31/39) of MGTs with positive expression of ER, including all of benign tumors and 66.7% (16/24) of malignant tumors. Benign tumors had more expression of ER than malignant tumors (p<0.01). Bcl-2 protein was detected in 61.5% (24/39) of MGTs which included 66.7% (10/15) of benign tumors and 58.3% (14/24) of malignant tumors. There was no significant difference in Bcl-2 expression between benign and malignant tumors. Malignant tumors showed more growth fraction and AI value than benign tumors (p<0.01), and the TUNEL index of all specimens examined was less than 1%. The analysis of correlation displayed that the expression of ER seemed to be positively related with Bcl-2 expression like those reported in breast cancer. However, there was no statistically significant correlation. The degree of cell proliferation and apoptosis were not significantly correlated to the expression of Bcl-2. There was positive relationship between cell proliferation and apoptosis, but negative correlation between ER and cell proliferation. In conclusion, the positive correlation between ER and Bcl-2 in canine MGTs suggested ER may be the regulator of Bcl-2 protein as seen in human breast cancer. In addition, there were more and stronger ER and Bcl-2 expression but less cell proliferation and apoptosis in benign MGTs. In contrast to benign tumors, malignant tumors had decreased ER and Bcl-2 expression or intensity but increased proliferation and apoptosis. It is hypothesized that decreased dependence of estrogen, the effect of anti-apoptosis, and increased cell proliferation and apoptosis occur in tumor progression or malignancy of canine MGTs.
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