Pathology of Mouse Models of Accelerated Aging.

Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience," which aims at elucidating the molecular mechanisms involved in aging. Progeroid mouse models are frequently used in geroscience as they provide insight into the molecular mechanisms that are involved in the highly complex process of natural aging. This review provides an overview of the most commonly reported nonneoplastic macroscopic and microscopic pathologic findings in progeroid mouse models (eg, osteoporosis, osteoarthritis, degenerative joint disease, intervertebral disc degeneration, kyphosis, sarcopenia, cutaneous atrophy, wound healing, hair loss, alopecia, lymphoid atrophy, cataract, corneal endothelial dystrophy, retinal degenerative diseases, and vascular remodeling). Furthermore, several shortcomings in pathologic analysis and descriptions of these models are discussed. Progeroid mouse models are valuable models for aging, but thorough knowledge of both the mouse strain background and the progeria-related phenotype is required to guide interpretation and translation of the pathology data.

Beyond Parasitism: Hepatic Lesions in Stranded Harbor Porpoises (Phocoena phocoena) Without Trematode (Campula oblonga) Infections.

The liver can be an indicator of the health of an individual or of a group, which can be especially important to identify agents that can cause disease in multiple species. To better characterize hepatic lesions in stranded harbor porpoises (Phocoena phocoena), we analyzed the livers from 39 porpoises that stranded along the Dutch coast between December 2008 and December 2012. The animals were selected because they had either gross or histologic liver lesions with minimal autolysis and no evidence of trematode (Campula oblonga) infection. The most common finding was a chronic hepatitis (22/39, 56.4%) that was often associated with significant disease reported in another organ system (18/22, 81.8%), of which 14 had chronic systemic disease. One case of chronic hepatitis was so severe as to mimic lymphoma, which could only be differentiated with immunohistochemistry. The other common lesions were lipidosis (11/39, 28.2%) and acute hepatitis (6/39, 15.4%), often in combination with mild chronic changes. Overall, although there were no consistent trends in etiology for the hepatic lesions, lipidosis was associated with starvation (8/11, 72.7%) and acute disease, and acute hepatitis was associated with bacterial infections and sepsis (6/6, 100%).

Expression of p53, Ki67, EcPV2- and EcPV3 DNA, and viral genes in relation to metastasis and outcome in equine penile and preputial squamous cell carcinoma.

REASONS FOR PERFORMING STUDY: Equine penile and preputial squamous cell carcinoma (SCC) is a potentially lethal disease of which little is known regarding the relationship between tumour characteristics and prognosis. OBJECTIVES: To assess the relationship between tumour differentiation grade (tumour subtype), presence of papillomaviruses, expression of viral genes (E2, E6, L1), nuclear proteins p53 and Ki67 and metastasis in equine penile and preputial SCC and to assess the relationship of tumour subtype, presence of papillomavirus type 2, p53 and Ki67 with survival. STUDY DESIGN: Retrospective case-control study using archived material. METHODS: Samples (n = 103) from 87 horses with penile and/or preputial intraepithelial neoplasia (PIN), papilloma or SCC and corresponding case files were evaluated. Tumours were graded microscopically and p53 and Ki67 expression evaluated immunohistochemically. Equine papillomavirus (EcPV) types 2 and 3 DNA was detected by conventional PCR. Real-time PCR was used for quantification of E2, E6 and L1 mRNA. RESULTS: Equine papillomavirus type 2 DNA was detected in 89.4% and EcPV3 in 1.5% of horses. No differences in quantitative expression of E2, E6 and L1 oncogenes between subtypes were found. Expression of p53 and occurrence of metastasis were positively correlated to a less differentiated subtype (r = 0.429, P<0.001 and r = 0.769, P = 0.001, respectively). Differences in survival between subtypes were significant (log Rank P<0.001); horses with less differentiated tumours were more likely to die of the disease (papilloma 8.3%; G1 26.1%; G2 26.3%; G3 63.3%). CONCLUSIONS: In equine penile and preputial SCC, tumour grading is an important prognosticator for survival and a predictor for presence of metastases. Expression of p53 and Ki67 and presence or expression of EcPV2 and EcPV3 do not appear to be important prognosticators.

Expression of cyclo-oxygenases-1 and -2, and microsomal prostaglandin E synthase-1 in penile and preputial papillomas and squamous cell carcinomas in the horse.

REASONS FOR PERFORMING STUDY: Penile and preputial papilloma and squamous cell carcinoma (SCC) are commonly diagnosed in horses. Papillomas have the potential to progress to potentially lethal SCC. Knowledge of pathogenetic mechanisms may help in prevention and definition of treatment targets. STUDY DESIGN: Retrospective study using archived material. OBJECTIVES: To determine the expression of cyclo-oxygenase 1 (COX-1), cyclo-oxygenase 2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) in penile and preputial normal tissue, papilloma and SCC in horses, and whether expression of these enzymes is influenced by degree of inflammation and differentiation grade. METHODS: Tumour differentiation grade, degree of inflammation and COX-1, COX-2 and mPGES-1 expression in 75 formalin-fixed paraffin embedded samples of penile and preputial papilloma and SCC of 68 horses were investigated by histopathology and immunohistochemistry. RESULTS: Inflammation was more prominent in SCC compared with papilloma. No correlation between expression of COX-1 or COX-2 and inflammation was found. Expression of mPGES-1 was weakly correlated with inflammation. Expression of COX-1, COX-2 and mPGES-1 was found in 42.6%, 50.7% and 96.0% of lesions respectively, but less than 1% of cells were immunopositive for COX-1 and COX-2 in 59.4% and 84.2% of cases respectively. Expression of COX-1 was moderately negatively correlated with differentiation grade, COX-2 was not correlated and mPGES-1 was poorly negatively correlated. CONCLUSIONS: Expression of COX-1 and COX-2 in penile and preputial SCC in the horse is poor and COX inhibitors may thus be of little value for prevention or treatment. Microsomal PGES-1 is more prominently expressed in well-differentiated tissue compared with poorly differentiated tissue. Further research on the role of mPGES-1 in carcinogenesis is needed to assess its potential use as a treatment target. Knowledge of arachidonic pathway enzyme expression and their role in equine penile and preputial carcinogenesis may help in developing preventive and therapeutic strategies.