ABSTRACT
Clinical and molecular similarities between canine mammary tumors (CMTs) and human breast cancer (HBC) propel scientists to further study their application in comparative oncology as a model for human breast cancer. In total, 64 canine mammary tumors were selected to study the most common markers, which are applicable for human breast cancer treatment, including estrogen and progesterone receptors (ER and PR), human epidermal growth factor (HER2/neu), Ki67, and cyclooxygenase 2 (Cox2). Immunohistochemistry (IHC) was used to assess the protein expression. The Veterinary Nottingham Prognostic Index (Vet-NPI) was also computed. Moreover, univariate and multivariable Cox proportional hazard analyses were applied to estimate hazard ratios (HRs). The results demonstrated that Ki67 was strongly expressed in the triple-negative tumors, and Ki67 protein expression continuously increased over the increase of Cox2 protein expression (p < 0.001). Further analysis revealed a significant difference among canine mammary subtypes and Vet-NPI, in which triple-negative tumors displayed the highest mean score compared to other subtypes (p < 0.001). In addition, the multivariable analysis revealed that the regional mastectomy procedure (adjusted HR = 2.78 (1.14-6.8)), the triple-negative tumors (adjusted HR = 48.08 (7.74-298.8)), strong Ki67 protein expression group (adjusted HR = 7.88 (2.02-30.68)), and strong Cox2 protein expression group (adjusted HR = 29.35 (5.18-166.4)) demonstrated significantly lower disease-free survival rates compared to other corresponding groups. Overall, canine mammary tumors showed strong similarities to human breast cancer in terms of clinical and molecular aspects; therefore, they could be suggested as a model for human breast cancer in comparative oncology.
ABSTRACT
Canine breast cancer (BC) and human BC are the most prevalent tumors in female dogs and humans, respectively. Several studies have indicated that canine BC is a good model for human BC. Unlike breast carcinomas, human primary breast lymphoma (PBL) is a rare tumor, but no case of canine PBL has been reported thus far. The current study presents a case of canine MC of the primary non-Hodgkin lymphoma (NHL) type for the first time and subsequently questions the theory of considering it as a model for human PBL. A 2-cm tumor was surgically removed from the left caudal abdominal mammary gland of a 6-year-old female dog of the terrier breed. Microscopic examination did not show any sign for the epithelial origin of the tumor. By contrast, histomorphological view and molecular pathological evaluation by immunohistochemistry showed that the tumor was of the diffuse large B-cell lymphoma (DLBCL) type [cluster of differentiation 19+ (CD19+), CD20+, CD10+, B-cell lymphoma 6+, CD3-, CD15-]. According to the World Health Organization classification, DLBCL is considered to be an NHL. Canine NHL is common in dogs and certain investigators believe that the biological behavior and clinical course is extremely similar to human NHL, and therefore, consider it as a model of human NHL. To the best of our knowledge, the current study is the first report of canine PBL. As the most significantly reported human PBL histotype is the DLBCL type, the histomorphological and immunophenotyping characteristics of canine PBL in the study considerably match with human PBL and raise the hypothesis that it can be a model for human PBL.
ABSTRACT
Canine malignant mammary gland tumors (CMMGTs) are the most common malignancies observed in females. Several biological similarities have been reported between CMMGTs and human breast cancer (HBC). The present study aimed to assess the correlation of vimentin filaments overexpression, as part of the process of epithelial-mesenchymal transition (EMT) and the clinicopathological characteristics in CMMGTs. The clinicopathological characteristics of 42 CMMGTs were collected. Paraffin-embedded blocks underwent immunohistochemistry staining, which was performed using vimentin (to assess the evolution of the EMT process), Ki-67 (for evaluation of tumor proliferation) and cluster of differentiation 34 (CD34) (for evaluation of angiogenesis) antibodies. The tumor stage, grade, vascular invasion, margin status, rate of expression of the vimentin filaments, microvessel density-CD34 and proliferation rate data were obtained. Finally, the association between the expression of the vimentin filaments and those parameters was resolved statistically. A significant association was shown between the overexpression of the vimentin filaments and tumor size (r=0.71, P=0.03), tumor grade (r=0.80, P=0.021), angiogenesis (r=0.57, P=0.043), proliferation coefficient (r=0.06, P=0.001) and vascular invasion (r=0.76, P=0.043). Vimentin overexpression did not statistically correlate with the tumor stage or the margin status. Similar to the findings of the present study, certain recent studies have indicated that vimentin filament expression in HBC and CMMGTs is associated with the severity of cancer. Thus, spontaneous canine mammary tumor models appear to be an appropriate animal model for breast cancer research, and the results of the present study could aid to reinforce the association.
ABSTRACT
BACKGROUND: Cervical cancer is the seventh most common malignancy in both genders combined and the third most common cancer in women. Despite significant progress in treatments, cervical cancer is not completely curable. Therefore, further research is necessary in this area. Animal models are one of the most practical tools in the field of cancer research. The present study aimed to characterize the growth behavior and surface markers of HeLa cells after heterotopic and systemic inoculation to athymic nude mice. METHODS: Ten 6-week old female athymic C57BL/6 nude mice were used in this study. HeLa cells were inoculated into the flank or tail vein. The tumor volume was calculated and growth curves were drawn. Tumor-bearing mice were sacrificed and the lesions obtained after harvesting were analyzed in a pathology lab. Subsequently, one slide per tumor was stained with hematoxylin and eosin (H&E) and other slides were stained immunohistochemically by cytokeratins (CK), vimentin, P53, CD34, and Ki-67. RESULTS: Tumor take rate, mean doubling time and latency period were 94.4%, 5.29 ± 3.57 days and 15.27 days, respectively. H&E results revealed highly malignant hyperchromatin epithelial cells. Immunohistochemical examination of the heterotopic tumors indicated greater expression of CK and less expression of vimentin compared to the metastatic ones. Sixty percent of cells were P53-positive and more than 80% were Ki-67-positive. CD34 expression indicated the intensity of angiogenesis in tumor. CONCLUSION: This study represents a comprehensive description of a HeLa xenograft model for in vivo investigations, enabling researchers to assess new treatments for cervical cancer.
