Feline Bowenoid in situ carcinoma (BISC) is a rare disease that presents as multiple discrete plaques of epidermal hyperplasia and dysplasia. Two studies using immunohistochemistry revealed papillomaviral antigens in 11% and 47% of BISCs. Additionally, a recent study detected papillomaviral DNA in 24% of BISC lesions. To further investigate the association between papillomaviruses and BISC, polymerase chain reaction using consensus primers was used to detect papillomaviral DNA in 18 formalin-fixed samples of BISC. Papillomaviral DNA was amplified from 11 of the samples but from none of the controls. Six amplicons were sequenced; one was homologous with a papillomavirus from a human patient with multiple cutaneous squamous cell carcinomas and the other five showed weak homology to human papillomavirus type 17. These five sequences were > 96% homologous over a 235 bp sequence, indicating the presence in all five BISCs of one papillomavirus type distinct from any previously sequenced and more closely related to human than animal papillomaviruses. The results confirm an association between BISC and papillomaviruses, and as all six papillomavirus sequences identified are closely related to human papillomaviruses, it is possible that the virus is transmitted from humans to cats or vice versa.
Squamous cell carcinomas (SCCs) are common skin tumours of cats. Previous studies have suggested that papillomaviral (PV) DNA is detectible within some feline SCCs. A PV DNA sequence has been previously amplified from five feline bowenoid in situ carcinomas (BISCs). Primers specific for this sequence were used in a nested polymerase chain reaction to compare PV detection rates in SCCs to rates within non-SCC skin lesions. Papillomaviral DNA was amplified from 20 of 20 BISC, 17 of 20 invasive SCC and 3 of 17 non-SCC controls. The rate of PV amplification from feline cutaneous SCCs was significantly higher than from non-SCC lesions. These results confirm that feline cutaneous SCCs are associated with PV infection. In humans, there is evidence that PVs promote SCC development within sun-exposed skin. The demonstrated association between PVs and feline cutaneous SCCs suggests, but does not prove, that PVs may also promote feline SCC development. If PVs are oncogenic in cats, prevention of PV infection may reduce feline cutaneous SCC development. To the authors' knowledge, this is the first time that PV DNA has been amplified from a non-SCC sample of feline skin.
For humans, strong evidence indicates that some mucosal papillomavirus (PV) types cause genital and oral neoplasia, and weaker evidence suggests that some cutaneous PVs may cause cutaneous squamous cell carcinomas (SCC). For nonhuman species, strong evidence supports a causal role of PVs in the development of feline and equine sarcoids. Likewise, PVs are believed to cause cutaneous SCCs in rabbits, western barred bandicoots, and some rodents. Furthermore, some evidence suggests that PVs may influence the development of both feline and canine cutaneous SCCs. This review discusses the evidence that PVs cause human cutaneous SCCs and the proposed mechanisms for this action. It then reviews preneoplastic and neoplastic skin diseases that are associated with PV infection in nonhuman mammals.
Abstract. Ten veterinary pathologists independently assigned histologic grades to the same 60 canine cutaneous mast cell tumors using the Patnaik classifications. The degree of agreement in grading among the pathologists was compared with the degree of agreement among the same pathologists in a previous study, in which each pathologist used the reference for grading that he/she uses routinely. Mean agreement improved significantly from 50.3% to 62.1% with uniform use of the Patnaik classifications (P ϭ 0.00001), suggesting that there is value in uniform application of a single grading scheme for canine cutaneous mast cell tumors. Agreement among pathologists was still not 100%, suggesting that a more objective grading scheme should be developed and that other histologic indicators of prognosis should be investigated.Key words: Dogs; grade; histopathology; mastocytoma.Mast cell tumors (MCTs) are the most common cutaneous tumors of the dog. 13 These tumors vary widely in their behavior, from nearly benign to highly invasive and metastatic. It has been recognized for more than 30 years that histologic grading is prognostic for the behavior of canine cutaneous MCTs. 3,6,10 The 2 most widely recognized grading systems classify MCTs into 3 grades based on histologic characteristics, including cellularity, cell morphology, invasiveness, mitotic activity, and stromal reaction. 3,10 Both grading systems correlate with the survival rate of canine patients with MCTs and histologic grade is the most important factor in determining the staging tests and adjunctive therapy that will be recommended for a dog with a cutaneous MCT. 9,13 Because of the importance of histologic grade in prognosis and decision making in the therapeutic management of dogs with MCTs, it is essential that veterinarians understand the variability among pathologists in assigning grades to MCTs. In a previous study, it was demonstrated that there was significant variation in the histologic grades assigned to the same 60 canine cutaneous MCTs by 10 veterinary pathologists at 1 institution. 8 Because variation in histologic grading was significantly associated with the use of different references describing grading systems, it was hypothesized that if all pathologists utilized the same reference for grading, there would be improved agreement in the grades as- signed to canine cutaneous MCTs. The objective of this study was to determine whether variation among veterinary pathologists in the histologic grading of canine cutaneous MCTs could be eliminated by uniform use of a single grading scheme.Ten veterinary pathologists independently graded the same 60 canine cutaneous MCTs as grade I, II, or III using the Patnaik classifications (Table 1). 10 These were the same 10 veterinary pathologists who participated in the previous study to evaluate variation among pathologists in histologic grading of canine cutaneous MCTs. 8 Four of these pathologists were from the University of Georgia College of Veterinary Medicine (UGA-CVM) Department of Pathology, 5 were from...
Isothiocyanates are a well-known class of cancer chemopreventive agents, and broccoli sprouts are a rich source of several isothiocyanates. We report herein that dietary administration to rats of a freeze-dried aqueous extract of broccoli sprouts significantly and dose-dependently inhibited bladder cancer development induced by N-butyl-N-(4-hydroxybutyl) nitrosamine. The incidence, multiplicity, size, and progression of bladder cancer were all inhibited by the extract, while the extract itself caused no histologic changes in the bladder. Moreover, inhibition of bladder carcinogenesis by the extract was associated with significant induction of glutathione S-transferase and NAD(P)H:quinone oxidoreductase 1 in the bladder, enzymes that are important protectants against oxidants and carcinogens. Isothiocyanates are metabolized to dithiocarbamates in vivo, but dithiocarbamates readily dissociate to isothiocyanates. We found that >70% of the isothiocyanates present in the extract were excreted in the urine as isothiocyanate equivalents (isothiocyanates + dithiocarbamates) in 12 h after a single p.o. dose, indicating high bioavailability and rapid urinary excretion. In addition, the concentrations of isothiocyanate equivalents in the urine of extract-treated rats were 2 to 3 orders of magnitude higher than those in plasma, indicating that the bladder epithelium, the major site of bladder cancer development, is most exposed to p.o. dosed isothiocyanate. Indeed, tissue levels of isothiocyanate equivalents in the bladder were significantly higher than in the liver. In conclusion, broccoli sprout extract is a highly promising substance for bladder cancer prevention and the isothiocyanates in the extract are selectively delivered to the bladder epithelium through urinary excretion. [Cancer Res 2008;68(5):1593-600]
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