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Ocular medulloepitheliomas, adenomas and adenocarcinomas share a common phenotype and originate from the optic cup neuroectoderm. This can make it very difficult to differentiate between these tumors histopathologically. Therefore, this study focused on identifying a combination of immunologic markers that might be used in the diagnosis of these tumors. These markers included AE1/AE3, CK7, CK20, and telomerase reverse transcriptase (TERT). Routine immunohistochemical staining was performed on 27 whole globes diagnosed with one of these tumors. The tumors that immunostained for TERT showed increasing immunoreactivity as the tumor types increased in aggressiveness. None of the tumor types were immunopositive for CK7. CK20 immunostaining was found in the adenomas but not in the adenocarcinomas or medulloepitheliomas. AE1/AE3 expression was present more consistently in the adenocarcinomas and less frequently in the adenomas. AE1/AE3 expression was present in only one of six medulloepitheliomas. Furthermore, CK20 and TERT showed inverse expression patterns, i.e. TERT increased in expression and CK20 decreased in expression with increasing aggressiveness. These results may be important diagnostic and prognostic indicators for these tumors.

Tyrosinase-related protein-2 (TRP-2) is a highly conserved melanogenic enzyme expressed in both pigmented and unpigmented melanomas of the mouse. To determine whether TRP-2 would be a good diagnostic marker for amelanotic melanomas of the dog, we performed immunohistochemistry for TRP-2, S-100, and Melan A on 21 canine tumors identified as amelanotic melanomas based on routine histopathologic examination. Thirteen of the tumors were TRP-2 positive, 10 were Melan A positive, and 19 were S-100 positive. TRP-2 was expressed in the cytoplasm of tumor cells in both primary and metastatic melanomas. S-100 staining was positive in all of three schwannomas and two of three gastrointestinal stromal tumors (one fibrosarcoma and one leiomyosarcoma) tested. Neither Melan A nor TRP-2 antibodies reacted with these tumors. Our findings indicate that staining for TRP-2 is a sensitive and specific method for confirming the diagnosis of amelanotic melanoma in dogs.

Summary Chronic exposure of the South American opossum, Monodelphis domestica , to ultraviolet radiation (UVR) induced 154 primary tumours of the cornea in 152 eyes. Tumours developed gradually; frank neoplasia was preceded by non-neoplastic proliferation of corneal stromal fibroblasts (keratocytes) and extensive neovascularization. Histologically, the majority of tumours (134 of 154) appeared to be fibrosarcomas arising from keratocytes, but about 12 per cent of the tumours (18 of 154) had a highly vascular appearance, suggesting haemangiosarcoma. In two eyes, squamous cell carcinomas overlay mesenchymal tumours. Ultrastructural features of UVR-induced corneal tumours were consistent with tumours of mesenchymal origin. Eye tumours, cell lines derived from eye tumours, and cultured skin fibroblasts expressed high content of messenger RNA for the intermediate filament vimentin; no cytokeratin messenger RNA was detected in these cells and cell lines. Based upon their light microscopic, ultrastructural, and intermediate filament biosynthetic characteristics, the majority of UVR-induced corneal tumours in M. domestica appeared to be fibrosarcomas. Haemangiosarcomas constituted a smaller proportion of the tumours, and squamous cell carcinomas were very rare.

Many tumor cells have elevated rates of glucose uptake that can be measured quantitatively, noninvasively and repeatedly by positron emission tomography (PET) with 2-deoxy-2-[ 18 F]-fluoro-D-glucose ( 18 F-FDG). Clinical imaging with 18 F-FDG PET has been used for detection and staging of primary and metastatic tumors. High-resolution microPET scanning and murine cancer models make it possible to analyze longitudinally glucose metabolism during the appearance, development and progression of individual experimental tumors. In this study, we used 18 F-FDG microPET and micro computerized tomography (microCT) to investigate glucose uptake in the DMBA/TPA chemically-induced multistage mouse skin carcinogenesis model. 18 F-FDG uptake is significantly higher in all papillomas than in surrounding skin. Elevated 18 F-FDG uptake is observed when tumors can be identified morphologically, but not before. Although 18 F-FDG uptake is high in all fully invasive, malignant skin squamous cell carcinomas, uptake in papillomas and microinvasive malignant squamous cell carcinomas is variable and does not exhibit any correlation with tumor stage.

There is currently great interest worldwide in developing noninvasive methods for the delivery of vaccines for upper respiratory tract diseases, including middle ear infection (otitis media, OM). One such noninvasive approach believed to have great potential for the prevention of diseases of the airway is to deliver vaccines by the intranasal (i.n.) route. Induction of a local, mucosal immune response in the upper respiratory tract, and particularly in the nasopharynx, would be a highly efficacious approach to prevention of OM. The chinchilla is the preferred rodent host for studying OM. However, although the anatomy of the chinchilla vomeronasal organ, inner ear, middle ear and Eustachian tube have been well-studied, to date there have been no reports in the literature of a similar complete analysis of the nasopharynx and nasal cavities of the chinchilla. In order to develop a relevant animal model of i.n. delivery as a potential immunization approach for the prevention of OM and to use these models for preclinical assessments of various vaccine candidates, it was important that we better understand the anatomy of the chinchilla nasal cavities and nasopharynx. Our anatomical studies revealed that the naso- and maxilloturbinates of the chinchilla nasal cavity more closely resemble the simple turbinates found in other rodents rather than the branched or complex turbinates seen in dogs, cats, and rabbits thus facilitating the i.n. delivery of vaccine candidates. The chinchilla nasal mucosa also contains numerous lymphoid aggregates like that of other rodents. Our findings thus suggest that we will be able to deliver i.n. vaccines effectively to chinchillas and that these vaccines will likely be able to induce specific immune responses.

Corneal tumours were induced in almost 100% of grey, short-tailed South American opossums ( Monodelphis domestica ) exposed three times weekly to ultraviolet radiation (UVR) for periods of a year or more. Five tumours, representing the morphological spectrum of UVR-induced corneal tumours (two fibrosarcomas, one malignant fibrous histiocytoma, one putative haemangiosarcoma, and one squamous cell carcinoma overlying a sarcoma), were assayed immunohistochemically for reactivity with antibodies against the intermediate filaments vimentin, smooth muscle actin (α isoform), muscle-specific actins (α and γ isoforms), desmin and cytokeratin, and with antibodies against the vascular endothelial marker von Willebrand factor. The squamous cell carcinoma was cytokeratin-positive. Other tumours were cytokeratin-negative and vimentin-positive. Three tumours had scattered individual cells and groups of cells immunoreactive with antibodies against smooth muscle actin and muscle-specific actins; two tumours (a fibrosarcoma and the malignant fibrous histiocytoma) had small numbers of desmin-positive cells. The putative haemangiosarcoma contained two populations of neoplastic cells, von Willebrand factor-positive vascular endothelial cells and smooth muscle actin-positive spindle cells. It was concluded (1) that UVR-induced corneal tumours may be composed of cells derived from resident epithelial cells, immigrant vascular endothelial cells, or fibroblast-like cells of unknown origin, and (2) that such tumours may contain more than one neoplastic cell type.

S-100 proteins are abundant in melanocytes of the skin; thus, S-100 immunoreactivity has been used as a diagnostic criterion for melanoma in humans and other placental mammals. We tested cutaneous melanomas of two marsupials, a bird, and a snake for S-100 immunoreactivity, using a polyclonal rabbit antibovine S-100 antibody. The tumor from a Tasmanian Pademelon ( Thylogale billardierii) was composed of large epithelioid cells, most of which had S-100–positive cytoplasm. In general, there were only scattered individual spindle-shaped S-100–positive cells or groups of cells in the primary mass from a Spotted-tailed Quoll ( Dasyurus maculates); S-100 staining was primarily nuclear. Cells comprising the melanomas of the Australian Cormorant ( Phalacrocorax carbo) and the Death Adder ( Acanthophis antarcticus) were S-100–negative, although peripheral nerve bundles in both were S-100–positive.

S-100 immunoreactivity was determined 1) in foci of melanocytic hyperplasia, 2) in naturally occurring, ultraviolet radiation-induced, and 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced primary melanomas, and 3) in metastatic melanoma lesions in the South American opossum Monodelphis domestica. Preneoplastic lesions of melanocytic hyperplasia contained scattered cells with S-100-positive nuclei. All primary melanomas, with the exception of a single DMBA-induced tumor, contained cells with S-100-positive nuclei. The pattern of S-100 reactivity in tumors varied from large foci of S-100-positive cells to scattered individual S-100-positive cells. Lymph node metastases were S-100 positive, but metastatic masses in internal organs were usually S-100 negative. Although S-100 reactivity did not distinguish preneoplastic lesions from tumors or benign melanomas from malignant melanomas, identification of metastatic tumor cells clearly demonstrated malignancy.

A total of 19 male and 21 female South American opossums ( Monodelphis domestica) were exposed to 250 J/m2 ultraviolet radiation from FS-40 sunlamps (280-400 nm) three times weekly for 70 weeks. The backs of the opossums were shaved as necessary to remove hair. In order to prevent photoreactivation of ultraviolet radiation-induced pyrimidine dimers by the light-dependent photolyase enzyme of the opossum, ultraviolet radiation-exposed opossums were housed under red lights (600-800 nm). The opossum photolyase requires light in the 320-450 nm range for its activity. Twenty-nine control opossums (14 males and 15 females) were irradiated by fluorescent lights with emission spectra primarily in the visible light range (320-700 nm); these control opossums were also housed under red lights, and their backs were also shaved to remove hair. No skin tumors were observed in control opossums, while ultraviolet radiation-exposed opossums developed a variety of hyperplastic and neoplastic skin lesions on the backs and on a single ear. Hyperplastic lesions included foci of epithelial hyperplasia, dermal fibroplasia, and focal proliferation of dermal melanocytes. A total of 20 ultraviolet radiation-exposed opossums (50%) developed skin tumors, and 13 opossums (32.5%) had more than a single tumor. Epithelial tumors included 25 papillomas, four keratoacanthomas, seven carcinomas in situ, three microinvasive squamous cell carcinomas, two invasive squamous cell carcinomas, and a single basal cell tumor. Ten dermal spindle cell tumors also occurred; most of these appeared to be fibrosarcomas. Two benign melanomas and one malignant melanoma were observed.