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ABSTRACT: P-cadherin is a classical cadherin expressed by myoepithelial cells in mammary tissue. Its expression in human breast cancer has been associated with aggressive tumour behaviour. To analyse the possible role of P-cadherin in canine mammary carcinogenesis, its expression was examined immunohistochemically in 82 samples of normal (n=2), hyperplastic (n=11) and neoplastic (n=69) canine mammary tissues. In normal and hyperplastic canine mammary glands, P-cadherin was restricted to myoepithelial cells, usually at sites of cell-to-cell contact. In tumour tissues, however, P-cadherin expression was observed in both epithelial and myoepithelial cells, with a cytoplasmic pattern of cellular distribution. Aberrant epithelial P-cadherin immunolabelling was found in 19/44 (43%) benign tumours and in 16/25 (64%) malignant tumours (P<0.001). In malignant tumours, a significant correlation between P-cadherin expression intensity and histological type was observed (P<0.05).
Journal of Comparative Pathology 02/2004; 130(1):13-20. · 1.65 Impact Factor
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ABSTRACT: Several immunohistochemical markers have been used to demonstrate the presence of myoepithelial cells in order to determine their role in the histogenesis of mammary tumors. p63, a recently characterized p53 homologue, is consistently expressed in myoepithelial cells of the human breast; however, no assessment of its immunoreactivity has been reported so far in canine mammary tissues. We investigated p63 immunohistochemical expression, as a novel myoepithelial cell nuclear marker, in 81 samples of normal (n = 2), hyperplastic (n = 11), and neoplastic (n = 68) canine mammary tissues. Myoepithelial phenotype was confirmed by using complementary monoclonal antibodies: alpha-smooth muscle actin, cytokeratin 14, cytokeratin AE1/AE3, and vimentin. p63 expression was observed in 91.4% (74/81) of the samples evaluated. Normal mammary glands, mammary hyperplasias, and benign tumors showed 100% immunoreactivity, with p63 expression restricted to myoepithelial cell nuclei. In general, benign mixed tumors showed a basal cell compartment immunoreactive to p63, with a gradual decrease of its expression during myoepithelial transformation. p63 expression was found in 72% of malignant tumors, allowing myoepithelial or basal cell identification in spindle-cell carcinomas (2/2), tubulopapillary carcinomas (8/9), solid carcinomas (7/10), and carcinosarcomas (1/3). The osteosarcoma analyzed was p63 negative. In our series, stromal components were consistently nonreactive to p63. In conclusion, the present study reveals p63 as a sensitive and highly specific marker of myoepithelial cells in canine mammary tissues, and the authors suggest p63 as an additional marker for defining myoepithelial histogenesis.
Veterinary Pathology 08/2003; 40(4):412-20. · 1.95 Impact Factor
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ABSTRACT: Secretory carcinoma is an uncommon variant of breast cancer, characterized by the presence of intracellular and extracellular eosinophilic secretion. Here, we report the cytologic, histologic, and immunohistochemical findings of a secretory carcinoma diagnosed in the left inguinal mammary gland of a 3-year-old female German Shepherd Dog. The fine-needle aspiration cytology showed numerous large branching sheets of neoplastic cells and isolated cells with cytoplasmic vacuoles. Histologically, the tumor was composed of cells with clear cytoplasm and prominent vacuoles that pushed the nuclei to the periphery, resembling signet ring cells. These cells were arranged in solid or tubular structures with lumenal spaces filled with eosinophilic secretion. Immunohistochemical reactions to cytokeratin (CAM 5.2) and alpha-lactalbumin were strongly positive in all neoplastic cells, and staining for vimentin and S100 protein was negative. The cytomorphologic and immunohistochemical features of this tumor are similar to those seen in tumors in women, hence enabling the diagnosis of a rare case of primary secretory carcinoma of the canine mammary gland.
Veterinary Pathology 12/1999; 36(6):601-3. · 1.95 Impact Factor
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ABSTRACT: To verify the potential role of fine needle aspiration (FNA) cytology in obtaining malignant cells from primary breast cancer for establishment of a primary breast cancer cell line.
In four patients with primary breast cancer subjected to FNA for diagnostic purposes, we attempted to establish primary cultures. We successfully obtained one primary cell line, originating in micropapillary invasive breast carcinoma. FNA material obtained under sterile conditions was centrifuged, and the cell pellet was washed with Dulbecco Modified Medium. The resulting suspension was seeded in 25-cm2 tissue culture flasks. The flasks were maintained with released caps in a 37 degrees C incubator with a humidified atmosphere of 5% CO2 in air. After one week, cells attached to the bottom of the flasks and began proliferating. When a culture became confluent, the cells were treated with 0.05% trypsin/0.02% EDTA in a PBS solution and subcultured. The flasks were observed daily with an inverted microscope, and culture passages were performed weekly.
The cell line obtained was named I2FPRW and exhibited morphologic and immunohistochemical features of epithelial cells of mammary origin. The cells were positive for cytokeratins (AE1/AE3 and CK 7), EMA and c-erbB-2. At this writing, this cell line was in the 15th passage of subculturing in the flasks with 10% FBS.
In the present study we demonstrated that is possible to establish a breast cancer cell line from material obtained by FNA cytology. FNA seems to be a valuable method of obtaining malignant cells from breast cancer able to grow free of fibroblasts in cell cultures.
Acta cytologica 43(6):985-90. · 0.49 Impact Factor
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ABSTRACT: p63, cytokeratin (CK) 5/6 and CK 14 have been employed in diagnostic pathology as markers of basal, squamous and myoepithelial differentiation in several types of human neoplasms; however, there is scant data on the concurrent expression of these markers in large series of human neoplasms. We analyzed the distribution of these three immunohistochemical markers in 51 normal human tissue samples, 350 carcinomas, 25 malignant melanomas (MMs), and 25 glioblastomas using three serial sections of tissue array research program (TARP)-4 multi-tumor tissue microarray. Also, we performed double immunostainings to characterize the differential distribution of p63/CK 5/6 and p63/CK 14 in normal breast, salivary gland and skin. p63, CK 5/6 and CK 14 were expressed in basal cells of the prostate and respiratory epithelia and in breast and bronchial myoepithelial cells. p63 was also expressed in cytotrophoblast cells of human placenta and in scattered cells of lymph node germinal center. CK 5/6 and CK 14 also stained the cytoplasm of basal cells of esophageal stratified, squamous epithelium and transitional epithelial cells of the bladder. No mesenchymal, neural, endothelial, smooth muscle or adipose cells were stained by any of the markers. p63, CK 5/6, and CK 14 were respectively expressed in 92.6%, 75.0%, and 52.9% of the squamous cell carcinomas of the lung, 10.2%, 20.0%, and 7.4% of the ductal carcinomas of the breast, 12.9%, 34.4%, and 11.8% of the serous and 25.0%, 0%, and 0% of the endometrioid carcinomas of the ovary. Lung, prostate and colonic adenocarcinomas, as well as MMs and glioblastomas were only rarely decorated by one of the markers. Only matched samples of 16 squamous cell carcinomas and two ductal carcinomas of the breast co-expressed these three markers. In double immunostainings, p63-CK 5/6, as well as p63-CK 14 were co-expressed by basal/ myoepithelial cells of the salivary glands and basal cells of the epidermis. Our results demonstrate that p63, CK 5/ 6 and CK 14 may be used together in immunohistochemical panels to characterize squamous differentiation in poorly differentiated carcinomas or carcinomas of unknown origin.
