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P-glycoprotein (Pgp) is a transmembrane protein pump involved in drug resistance in canine and human lymphoma. There are no published clinical studies evaluating Pgp expression in feline lymphoma. The purpose of this study is to evaluate the level of Pgp expression in feline lymphoma and correlate it with clinical outcome. Two human Pgp monoclonal antibodies, C219 and C494, were used to detect Pgp expression in tissue samples from 63 cats with lymphoma. Demographic results appear comparable to recently published feline lymphoma studies. The Kaplan–Meier median remission and survival times were 164 and 571 days, respectively. Fourteen cats had positive expression of Pgp using MAb C219, and 40 were positive with C494. Variables statistically associated with survival included bone marrow involvement, stage, substage, and use of radiation therapy as a part of treatment. Pgp expression as assessed by MAb C219 and C494 is not predictive of remission or survival time in cats with lymphoma. [ABSTRACT FROM AUTHOR]

Multicentric squamous cell carcinoma in situ (MSCCIS) is a variant of squamous cell carcinoma in cats, commonly referred to as Bowen’s-like disease. Imiquimod 5% cream (Aldara™) is a novel immune response modifier (IRM) that has been reported as a successful treatment for Bowen’s disease in humans. The purpose of this study was to describe clinical findings, treatment protocols and survival in cats with MSCCIS treated with imiquimod 5% cream and to examine the effects of imiquimod 5% cream in cats with MSCCIS. The expression of papillomavirus group-specific antigen in the study population was also determined. From review of medical records, 12 cats were identified with a histologic diagnosis of MSCCIS and treatment with imiquimod 5% cream. Initial lesions responded to imiquimod 5% cream in all cats. Most cats (75%) developed new lesions. New lesions also responded to imiquimod 5% cream in all cats treated. Five cats (41%) had side effects suspected to be associated with the use of imiquimod 5% cream, including local erythema (25%), increased liver enzymes and neutropenia (8%), and partial anorexia and vomiting (8%). Kaplan–Meier median treatment duration and median survival time probabilities for cats in this study were 1189 days, respectively. A time to failure model was generated as many cats were censored from analysis well before the aforementioned projected median. This model resulted in a shorter median survival time of 243 days. No patient-related, tumour-related or treatment-related prognostic variables were identified. No expression for papilloma group-specific antigen was found. Imiquimod 5% cream appears to be well tolerated in the majority of cats, and further studies are warranted to further examine its usefulness in cats with this disease. [ABSTRACT FROM AUTHOR]

Mammary gland tumours (MGT) are the third most common tumours in the cat. At least 85% are malignant and metastasis is common. The HER-2/neu protooncogene encodes a 185-kDa transmembrane tyrosine receptor kinase protein. Approximately 25–30% of human MGT demonstrate HER-2/neu protein overexpression in the malignant cells, and overexpression has been associated with an increased metastatic propensity and a decreased prognosis. No reports have been published, to date, investigating the expression of Her-2/neu in cats or cats with spontaneous mammary tumours. Based on the increased percentage of malignant mammary cancers in cats, compared to that in dogs, and the correlation of an increased malignancy and a decreased prognosis with Her-2 overexpression in human mammary cancer, we hypothesized that cats with spontaneous malignant mammary adenocarcinoma overexpress Her-2/neu in the neoplastic mammary epithelial cells. Thirty cats with MGT were assayed for Her-2/neu immunohistochemical expression. The median percentage of cells from feline MGT expressing Her-2/neu by utilizing the Dako polyclonal and CB11 monoclonal antibodies was 85 and 92.5, respectively. Her-2/neu expression intensity grades 2 and 3 consistent with the overexpression by utilizing the Dako polyclonal and CB11 monoclonal antibodies were observed in 90 and 76.7% of cats with MGT, respectively. The level of overexpression concordance across the two antibodies was 70%. The results from this study suggest that Her-2/neu overexpression is common in cats with spontaneous MGT, and therefore appears to represent an excellent model for Her-2/neu-overexpressing human breast cancer. [ABSTRACT FROM AUTHOR]

Adrenal cortical epithelial tumours are common in ferrets. A variant tumour type with prominent spindle cell proliferation has been identified. We characterized these variant tumours with light microscopy and immunohistochemical analysis and correlate these features to clinical parameters and prognosis.We classified 24 ferret adrenal cortical masses with recognizable spindle cell proliferation obtained from the AMC and AFIP databases, based on percentage of spindle cells present and features of malignancy. These masses were separated into hyperplastic nodules and adenomas (both with 1–24% spindle cells),‘mixed’ adenomas (≥25% spindle cells), adenocarcinomas (1–24%) and‘mixed’ adenocarcinomas (≥25% spindle cells). Tumours were evaluated immunohistochemically for smooth muscle actin (SMA) and estrogen receptor (ER) expression. Disease-free interval (DFI) and survival time (ST) were calculated using Kaplan–Meier product limit method.Of 24 cases of spindle cell variant adrenal tumours, one was a hyperplastic nodule, 10 were adenomas, three were‘mixed’ adenomas, six were adenocarcinomas and four were‘mixed’ adenocarcinomas. The proliferative spindle cell cytoplasm was SMA-positive (smooth muscle myocyte origin). ER positivity, seen in nine of 24 cases, was restricted to adenocarcinomas,‘mixed’ adenomas and‘mixed’ adenocarcinomas. DFI and ST were significantly reduced in‘mixed’ adenocarcinomas or tumours with ER expression. DFI was significantly reduced in tumours with marked smooth muscle.The spindle cell component of these variant adrenal tumours is smooth muscle in origin. The presence of abundant smooth muscle, a more malignant histologic grade (‘mixed’ adenocarcinomas) and ER expression are significantly positively correlated to both decreased DFI and decreased ST. [ABSTRACT FROM AUTHOR]

Canine malignant melanoma(CMM) is an aggressive neoplasm treated with surgery and/or fractionated RT; however, metastatic disease is common and chemoresistant. Preclinical and clinical studies by our laboratory and others have shown that xenogeneic DNA vaccination with tyrosinase family members can produce immune responses resulting in tumor rejection or protection and prolongation of survival. The potency of DNA vaccines can be further enhanced by adding DNA encoding cytokine genes. We have shown in preclinical mouse models that GM-CSF DNA enhances immune responses and tumor protection. These studies provided the impetus for murine tyrosinase(muTyr) ± human GM-CSF(huGM-CSF) DNA vaccination in CMM.Two groups of five dogs each with advanced(WHO stage II-IV) CMM received four biweekly IM injections(100 ug or 500 ug, respectively/vaccination) of plasmid DNA encoding muTyr via the Biojector2000 jet delivery device. Subsequently, three groups of nine dogs each with advanced CMM received four biweekly IM injections of plasmid DNA encoding muTyr(50 ug), huGM-CSF(3 dogs each at 100/400/800 ug) or both.Minimal to mild pain was noted on vaccination and no toxicity or induction of autoimmunity was seen. The KM median survival time was 224 days(100/500 ug muTyr), 278 days(50 ug muTyr), 140 days(huGM-CSF) and>265 days(muTyr&huGM-CSF; 6 dogs still alive).The results of these trials demonstrate that xenogeneic DNA vaccination continues to be a safe and potentially therapeutic modality for CMM. These results also warrant further evaluation of this novel therapeutic in a Phase II setting. [ABSTRACT FROM AUTHOR]

Xenogeneic melanosomal differentiation antigens, delivered in the form of a plasmid DNA vaccine, can overcome host immune ignorance/tolerance in preclinical animals to melanoma by: 1) generating humoral and cytotoxic T cell responses and 2) inducing protection from tumor challenge. Initial trials of human tyrosinase(huTyr) DNA vaccination of dogs with advanced malignant melanoma(Bergmanet al, 2003) demonstrated safety and prolongation of survival with this therapeutic modality. We investigated antigen-specific immunity in dogs receiving huTyr DNA vaccination.Three cohorts of three dogs each with advanced(WHO stage II-IV) canine malignant melanoma(CMM) received four biweekly IM injections(dose levels 100, 500, or 1,500 ug, respectively/vaccination) of huTyr plasmid DNA via the Biojector2000 jet delivery device. Sera samples were taken before and after vaccination to detect specific antibody formation to huTyr by Enzyme-Linked ImmunoSorbent Assays(ELISAs) and flow-cytometry.Three dogs have measurable, 2 to 4 fold huTyr-specific antibody titers. Preliminary studies by flow-cytometry have confirmed antibody response to huTyr by positive binding to endogenous human tyrosinase in SK-Mel188 cells using post-vaccinate serum.Xenogeneic(huTyr) DNA vaccination generates antigen-specific humoral responses, which may partially explain the previously reported clinical efficacy and anti-tumor responses. Ongoing studies include: 1) a comprehensive analysis by flow-cytometry to detect huTyr-specific antibodies and 2) a quantitative measure of potential cytotoxic T-cell responses in these dogs by the DNA vaccination. [ABSTRACT FROM AUTHOR]

The Patnaik grading system for canine cutaneous MCT is currently one of the best determinants of prognosis; however, clinical outcome does not always correlate with histologic grade. The development of molecular markers offers a potential advantage and may complement subjective grading. The primary purpose of this study was to correlate histologic grading to Ki67/PCNA/AgNOR/c-Kit scores. Thirty-eight dogs with cutaneous MCT underwent surgical resection. Tumors were graded, with expansion of grade II MCT to low, medium (or II only) and high. For statistical purposes, MCT grade I, II (low, medium, high) and III were assigned a score of 1, 2, 3, 4, or 5, respectively. Sections were processed for AgNOR staining and expression of PCNA, Ki67 and c-Kit as previously described (modified biotin-strepavidin with DAB substrate). Paraffin-embedded canine tissue arrays were used as positive and negative controls (primary antibody replaced with pre-immune sera). Parametric statistical testing was performed using Statview statistical software with P ≤ .05 as significant. There were 12, 20, 5 and 1 grade II low, grade II medium, grade II high and grade III MCT, respectively. The mean Ki67 score was 9.114 (median 8.0, range 1–28), mean PCNA score was 26.25 (median 24.0, range 5–65), mean AgNOR score was 1.499 (median 1.35, range 1.02–2.76) and c-Kit scores were +1 (9/37), +2 (19/37) and +3 (9/37). With parametric statistical testing, significantly positive correlations were found for Ki67/Grade, PCNA/Grade, AgNOR/Grade, Ki67/PCNA, Ki67/AgNOR and PCNA/AgNOR (all P < .0001). No significant correlation was found for c-Kit and grade; however, +3 c-Kit scores had statistically significantly higher grades than +2 c-Kit scores (P = .0458). Ki67/PCNA/AgNOR scores are positively correlated to grade in dogs with MCT. Further studies to correlate Ki67/PCNA/AgNOR/c-Kit scores with clinical variables are ongoing. [ABSTRACT FROM AUTHOR]