Host response to bovine ocular squamous cell carcinoma

Specific humoral and cellular immunologic responses to autologous and heterologous tumors were evaluated in 35 Hereford cows with ocular squamous cell tumors and in 6 healthy cows. Sera from 5 healthy cows and 23 ocular tumor-bearing cows were evaluated for antibody to tumor, using radioimmunoassay, passive hemagglutination, agglutination, and microagglutination assays with various soluble tumor antigen and whole tumor cell preparations. Antibody to tumor was detected in only 2 cows. Using the microagglutination assay, antibody to autologous and heterologous tumor cells was found in the sera of 2 cows inoculated intraocularly with purified, viable autologous tumor cells. Twenty-eight tumor-bearing cows and 3 healthy cows were evaluated for delayed-type hypersensitivity responses, using 5 tumor preparations; positive skin test responses were not observed.     

Bovine herpesvirus-5 (DN599) antigens in cells derived from bovine ocular squamous cell carcinoma.

Bovine herpesvirus 5 antigens were detected by indirect immunofluorescence in the cytoplasm of tumor cells derived from bovine ocular squamous cell carcinomas. The number of tumor cells expressing bovine herpesvirus 5 antigens was increased following exposure to ultraviolet light or maintenance in pH 8.4 media. Infectious virus could not be detected in homogenates of tumors or by explantation of tumors. However, medium removed from the ocular tumor explants induced cytoplasmic vacuolization, inclusions and syncytia when inoculated onto bovine fetal spleen monolayers. Acridine orange staining revealed these cytoplasmic inclusions to contain double-stranded deoxyribonucleic acid. These results provide evidence that bovine herpesvirus 5 may be associated with bovine ocular squamous cell carcinoma.     

Tumour-associated antigens in bovine ocular squamous cell carcinoma: studies with sera from tumour-bearing animals

Sera from 21 cattle (10 bovine ocular squamous cell carcinoma (BOSCC) bearing and 11 controls) were tested for antibody reactivity against various cultured cells (BOSCC, normal skin and tumours other than BOSCC), by an indirect immunofluorescence technique. Most of the BOSCC sera reacted with autologous and allogeneic BOSCC cells and did not show any significant reactivity with normal skin cells (autologous or allogeneic). These sera when further tested on 7 different allogeneic or xenogeneic tumour cell types (other than BOSCC), showed significant reactivity only with cultured equine sarcoid and cutaneous papilloma cells. Three of the BOSCC sera did not react with autologous BOSCC cells but reacted indiscriminately with all other allogeneic BOSCC, normal cells and other tumour cells. Most of the control sera did not show any significant reactivity against BOSCC cells except sera from one cow bearing ocular papilloma and 2 healthy normals that were in contact with BOSCC bearing animals. This study suggests that BOSCC cells possess tumour associated antigens that are common to most (if not all) BOSCC cells.     

Immunohistochemical studies of epithelial cell proliferation and p53 mutation in bovine ocular squamous cell carcinoma

Bovine ocular squamous cell carcinoma (OSCC) is the second most common cause of rejection due to neoplasia in slaughterhouses on Sao Miguel Island, Azores, and accounts for significant economic losses. To obtain a better insight into the genesis and neoplastic transformation process of bovine OSCC, abnormal protein expression and proliferation index were assessed by the immunohistochemical evaluation of p53 and Ki67, respectively. OSCC samples were collected from 15 bovines and were classified histologically according to the degree of differentiation into three categories: poorly, moderately, and well differentiated. Immunohistochemistry using polyclonal anti-human p53 antibody and polyclonal anti-human Ki67 antibody was performed. Ten of 15 tumors tested were immunoreactive for p53. Twelve tumors demonstrated Ki67 expression. As in human squamous cell carcinoma, p53 overexpression is frequent in bovine OSCC, providing support for a possible role of the protein in the pathogenesis of this neoplasia. No correlation between the percentage of p53 stained nuclei and the degree of differentiation was observed, although different patterns of staining were seen according to the degree of keratinization of the tumor cells. With the exception of the moderately differentiated OSCC group, Ki67 index showed significant correlation with the histologic pattern, increased proliferation being found in poorly differentiated OSCC (P = 0.013).     

Search for bovine papilloma virus DNA in bovine ocular squamous cell carcinomas (BOSCC) and BOSCC-derived cell lines.

Although the cause of bovine ocular squamous cell carcinoma (BOSCC) is attributed to viruses in addition to cofactors (eg, UV light), to our knowledge, the final causative agent has not been described. Bovine papilloma virus (BPV)-like particles were detected in approximately 33% of various putative precursor lesions of BOSCC. In contrast, it was reported that, using BPV-specific antibodies, it was not possible to detect viral antigens in BOSCC. Fourteen established BOSCC and 9 BOSCC-derived cell lines were examined for BPV DNA. Probes of all 6 known BPV types were used in various hybridization assays. Neither Southern blot analysis, under high and low stringency conditions, nor in situ hybridization resulted in detection of BPV DNA. Papilloma viruses were not observed in electron microscopic studies. Results exclude direct association between BOSCC and BPV types 1 to 6, or as yet unknown closely related BPV types. However, BPV may contribute to induction of precursor lesions or events leading to carcinogenic transformation, without being relevant for maintenance of the tumor.     

Bovine ocular squamous cell carcinoma: an epidemiological perspective.

Epidemiological studies on bovine ocular carcinoma were reviewed. Reports on the frequency and the distribution of the disease indicate that it is still a very prevalent and economically important disease. It is recognized throughout North America, but is more frequent in lower latitudes under range conditions. Etiological factors including ultraviolet light, circumocular apigmentation and viruses, as well as the pathogenesis, are considered in light of current knowledge on carcinogenesis of this tumor. It is likely that the induction of bovine ocular carcinoma is multifactorial and the precise roles played by each of the various factors are not yet understood.     

Bovine ocular squamous cell carcinoma: Ultrastructural characteristics in vitro

The ultrastructure of cells obtained from bovine ocular squamous cell carcinoma is described. Cells were observed in pelleted form and in monolayer in situ on film liners. Both preparations consistently showed the ultrastructural features of transformed epithelium in vitro.     

Controlling ocular squamous cell carcinoma in Hereford cattle

In 3 herds 737 Hereford cattle were examined for neoplastic ocular lesions at intervals ranging from 20 to 242 days. Initially all lesions greater than 3 mm diameter were treated by cryosurgery; smaller lesions were left untreated. At subsequent inspections, lesions which had increased to 5 mm diameter were treated. The prevalence of ocular lesions in the herds ranged from 8.1 to 45.7% at the commencement of the study, and from 1.5 to 8.8% after 3.5 years. In treated cattle 71% of lesions regressed after one or two treatments. Seventy-five percent of the small untreated lesions regressed. The progression of lesions and occurrence of new lesions was highest during summer and lowest during winter. It was concluded that inspection of eyes for lesions should be at intervals of 3 to 4 months, and include one during the summer. It is feasible for owners to detect and identify cattle with ocular lesions and to present for treatment those that have grown since the preceding inspection to a size nearing or exceeding 5 mm diameter.     

Bovine ocular squamous cell carcinoma: superoxide dismutase and catalase levels

Considerable evidence exists for the production of free radicals in the eye region after exposure to ultraviolet light. Failure to remove these radicals adequately may be important in the predisposition of Hereford cattle to ocular carcinoma. The levels of two enzymes, superoxide dismutase and catalase, involved in the removal of superoxide anion and hydrogen peroxide, were compared in Hereford cattle predisposed to ocular carcinoma and a resistant breed, Droughtmaster cattle. The results demonstrate comparable levels of superoxide dismutase in the two breeds in both eye tissue and erythrocytes. Catalase levels also were the same in both breeds. Increased incidence of ocular carcinoma in Herefords does not appear to be due to a deficiency in either superoxide dismutase or catalase.     

Cryosurgical treatment of ocular squamous cell carcinoma of cattle.

A total of 718 ocular squamous cell carcinomas of cattle were treated with various cryosurgical units and techniques during a 2.5-year study. In 609 of the lesions, a single freeze was used, with a cure rate (total regression) of 66%. In 109 lesions treated with a double freeze-thaw cycle (rapid freeze to - 25 C, and unaided thaw followed immediately by refreezing to -25 C), the cure rate was 97%. Cryosurgical units designed for delivery of liquid nitrogen provided a more rapid rate of freezing and, thus, a higher cure rate than did units designed for delivery of nitrogen vapor. It was concluded that cryosurgery for treatment of squamous cell carcinoma is a simple and rapid procedure; is economical; provides analgesia itself, due to sensory nerve injury; requires minimal preoperative and no postoperative medication; causes minimal side effects; may be repeated; and is excellent for use on suspect premalignant lesions.     

Cryosurgery of bovine squamous cell carcinoma of the vulva

Sixty-two cattle with vulval carcinoma of various sizes were treated by cryosurgery using double freeze-thaw cycles. A cure rate of 88.7 per cent was achieved. It was confirmed that the smaller the lesions the better the response and that in larger lesions failure occurred because of the difficulty in freezing the mass of neoplastic tissue rapidly to the lethal temperature of -25 degrees C using the cryosurgical unit available. It was concluded that, if instituted early in the clinical course of the disease, cryotherapy of bovine vulval carcinoma is superior to surgical excision but the cost of the equipment may be a limiting factor in its application in the field.     

Factors influencing morbidity and outcome of equine ocular squamous cell carcinoma

A retrospective review of 41 cases of equine ocular squamous cell carcinoma with follow up information for 33 horses is presented. An apparent prevalence in heavy horse breeds was identified. Age and sex distribution were similar to those previously reported. High recurrence (42.4 per cent) and low metastasis (6 per cent) rates were seen. Initial tumour location, primary treatment used, or patient case history had no apparent influence on final outcome. The willingness of owners to pursue with continuous treatment correlated with a high degree of success.