ABSTRACT. A 5-year-old, male Bichon-Frise dog presented with a cutaneous mass in the basal region of the auricle. Histologically, the cutaneous neoplasm was comprised of lobules with solid cellular proliferation separated by thin fibrous septa. Neoplastic cells varied in size, with moderate to abundant amounts of PAS-positive cytoplasm, large nuclei and prominent nucleoli. Immunohistochemical examinations showed that tumor cells were positive for pan-cytokeratin (CK) (AE1/AE3 and CAM5.2), CK8 and CK18, but negative for pan-CK (KL1), CK7, CK14, CK16 and CK20. Double-labeled immunofluorescence testing indicated that neoplastic cells frequently co-expressed CK and vimentin, suggesting divergent differentiation of tumor cells. Based on these findings, the tumor was diagnosed as canine clear cell adnexal carcinoma.

Abstract. Gastric cancer (GC) is one of the most common malignancies worldwide. In particular, scirrhous type GC is highly metastatic and is characterized clinically by rapid disease progression and poor prognosis. MicroRNAs (miRNAs) play crucial roles in cancer development and progression. We previously demonstrated by microarray analysis that microRNA-145 (miR-145) is one of the more highly expressed miRNAs in scirrhous type GC vs. non-scirrhous types of GC. In the present study, we investigated the role of miR-145 in scirrhous type GC. The expression levels of miR-145 assessed by quantitative RT-PCR were higher in scirrhous type GC tissue samples than in non-scirrhous type GC and corresponding normal tissues. GC patients with high miR-145 expression were at a more advanced tumor stage (P=0.0156) and had more scirrhous type histology (P=0.0054) than those with low miR-145 expression. Furthermore, miR-145 expression was significantly associated with poor prognosis in GC patients (P=0.0438). miR-145 expression was localized in stromal fibroblasts of scirrhous type GC but not in cancer cells. miR-145 was induced by treatment by transforming growth factor-β, and it enhanced the expression of α-smooth muscle actin, a marker of myofibroblasts, in both normal gastric fibroblasts and cancer-associated fibroblasts. These data suggest that miR-145 may contribute to the progression of scirrhous type GC by regulating activation of peri-tumoral fibroblasts.

Abstract. We report herein a case of collagenofibrotic glomerulonephropathy in a 3-year-old Shiba Inu with severe proteinuria. Histologically, renal glomeruli were enlarged with massive deposition of a homogeneous eosinophilic substance within the mesangium and capillary walls. The deposits reacted weakly with periodic acid-Schiff, stained deep blue with Masson's trichrome, and were positive by immunofluorescence for type III collagen and fibronectin. Ultrastructurally, the deposits consisted of fibrils and amorphous material in the mesangial matrix and beneath the glomerular capillary endothelium. The fibrils had transverse bands analogous to those of collagen fibrils. Electron microscopy also revealed focal detachment of podocytes and foot process effacement in glomerular tufts, which suggested that podocyte injury had contributed to the development of proteinuria in this dog. The current case resembles collagenofibrotic glomerulonephropathy (CFGN) in humans in histopathologic, immunofluorescence, and electron microscopic findings. This is the first report of CFGN in a nonhuman species with glomerular deposition of fibronectin and type III collagen.

Histopathological and immunohistochemical examinations were made on a cutaneous tumor on the head of an 11-year-old female mixed-breed dog. The tumor was well demarcated and comprised multilobular structures of neoplastic epithelial cells with abundant plump peritumoral stromal cells. The neoplastic cells formed irregular cell cords or trabeculae and were arranged in characteristic palisades at the periphery. Immunohistochemically, neoplastic cells were positive for p63 and the several cytokeratins examined. In contrast, the plump peritumoral stromal cells were positive for vimentin and unevenly for nestin, a neuroepithelial stem cell protein. The stromal cells prominently proliferated in proximity to epithelial neoplastic cells, suggesting a close interaction between these two cell types.

In humans, periostin plays a critical role in the enhancement and chronicity of allergic skin inflammation; however, whether it is involved in the pathogenesis of canine dermatitis remains unknown. The aim of this study was to examine the expression patterns of periostin in healthy, atopic, and nonatopic chronically inflamed canine skin. Biopsy specimens from 47 dogs with skin disease and normal skin tissue from 5 adult beagles were examined by light microscopy, immunohistochemistry, and in situ hybridization. In normal skin, periostin was localized just beneath the epidermis and around the hair follicles. In chronically inflamed skin, periostin expression was most intense in the dermis with inflammatory cell infiltrates. In contrast, low levels of periostin were detected in acutely inflamed and noninflamed skin. Conversely, all canine atopic dermatitis tissues characteristically showed the most intense expression of periostin in the superficial dermis, particularly at the epidermal-dermal junction. In situ hybridization showed that periostin mRNA was broadly expressed in the basal epidermal keratinocytes, outer root sheath cells, and dermal fibroblasts in normal dog skin. High expression of periostin mRNA was observed in fibroblasts in dog skin with chronically inflamed dermatitis. Moreover, in some chronically inflamed skin specimens, periostin mRNA expression was increased in basal keratinocytes. The severity score of chronic pathologic changes and CD3+ cell number in the dermis were correlated with distribution pattern of periostin in the atopic skin. These data suggest that periostin could play a role in the pathophysiology of chronic dermatitis, including atopic dermatitis, in dogs.