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This study aims to gather knowledge about the use of deoxycorticosterone pivalate (DOCP) by Western European Veterinarians (WEV) in dogs with typical hypoadrenocorticism. An observational cross-sectional study was conducted using an online survey, translated into four languages and disseminated to veterinary affiliates and mailing lists in six countries of Western Continental Europe. Respondents were tasked to share their therapeutic approach to hypoadrenocorticism, whether they preferred DOCP or fludrocortisone and the specific practical use of DOCP. One-hundred and eighty-four responses were included. Of these, 79.9% indicated that they preferred prescribing DOCP over fludrocortisone as a first-line treatment for mineralocorticoid supplementation. A total of 154 respondents had used DOCP at least once. Eighty percent of those who reported their initial dosage prescribed 2.2 mg/kg. After starting DOCP, 68.2% of the respondents assess electrolytes 10 and 25 days after administration following manufacturer instructions. In stable dogs, electrolytes are monitored quarterly, monthly, semi-annually, and annually by 44.2%, 34.4%, 16.9%, and 4.6% of respondents respectively. When treatment adjustment is required, 53% prefer to reduce dosage while 47% increase the interval between doses. Overall, DOCP is the preferred mineralocorticoid supplementation among WEV. Reported variability underlies the need to investigate the best strategies for DOCP use and therapeutic adjustments.

Aims: To compare survival in dogs with recurrent or metastatic insulinomas that were treated with palliative therapy, alone or in combination with toceranib phosphate and to assess tolerability of the combined therapy in dogs. Materials and methods: Dogs diagnosed with insulinoma were retrospectively identified in the records of the Veterinary Teaching Hospital Complutense (Madrid, Spain). Diagnosis of insulinoma was based on clinical signs of hypoglycaemia, concentrations in serum of glucose 10 μIU/mL and presence of a pancreatic mass on diagnostic imaging. Dogs were treated surgically or medically, according to clinical stage established by imaging techniques, and monitored with blood and urine analyses monthly and abdominal ultrasonography every 3 months until death. Dogs that presented with metastatic disease at diagnosis or with recurrent hypoglycaemia after surgery were treated, according to the owner's decision, with one of two treatment protocols: palliative therapy alone (control group, n=7: diet, prednisone, famotidine or omeprazole, ±octreotide) or palliative therapy in combination with toceranib (treatment group, n=5; median dose of toceranib 2.52 mg/kg). Overall survival time (OST) and adverse events were compared between the two treatment groups. Results: The OST was longer in the treatment group (median 399, min 125, max 476 days) compared to the control group (median 67, min 23, max 387 days; p=0.042). Dogs in the treatment group had a higher incidence of grade 1–2 gastrointestinal toxicity (diarrhoea) than dogs in the control group (p=0.010). In all cases, gastrointestinal toxicity was solved by temporarily discontinuing toceranib. Conclusions and clinical relevance: The use of toceranib combined with palliative treatment in dogs with suspect metastatic or recurrent insulinomas increased survival time and was adequate tolerated.

Canine inflammatory mammary cancer (IMC) is highly malignant, invasive, and a therapeutic challenge because effective medical treatment is still unavailable. This retrospective study compares the efficacy of an oral COX-2 inhibitor combined with toceranib phosphate and oral cyclophosphamide (multi-drug therapy, MT) with COX-2 inhibitor therapy alone (single-drug therapy, ST) in dogs diagnosed with secondary IMC. Clinical response, adverse events, overall survival time (OST), disease-free survival (DFS) and time to progression (TTP) were evaluated. Sixteen patients were included, eight received MT and eight receiving ST. Median OST was significantly higher in patients receiving MT (96.0 vs 37.5 days; p=0.046) and in patients with post-surgical rather than non-surgical IMC (86.5 vs 41.5 days; p=0.038). Additionally, median TTP was significantly higher in patients treated with MT (p=0.010). In patients with non-surgical IMC, the clinical benefit (CB) was reached in 100% (n=3) of patients receiving MT and in 33% (n=1) of those receiving ST; the response duration was significantly longer in MT cases (p=0.026). The absence of disease progression at day 30 of treatment was significantly associated with longer OST, DFS and TTP (p=0.018, p=0.002 and p

P-glycoprotein (P-gp/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) expression are frequently related to multidrug resistance (MDR) in neoplastic cells. Canine inflammatory and grade III noninflammatory mammary carcinomas (IMC and non-IMC) are aggressive tumors that could benefit from chemotherapy. This study describes the immunohistochemical detection of P-gp and BCRP in 20 IMCs and 18 non-IMCs from dogs that had not received chemotherapy. Our aim was to determine if P-gp and BCRP expression was related to the “inflammatory” phenotype, to establish a basis for future studies analyzing the response to chemotherapy in dogs with highly malignant mammary cancer. Immunolabeling was primarily membranous for P-gp with a more intense labeling in emboli, and immunolabeling was membranous and cytoplasmic for BCRP. P-gp was expressed in 17 of 20 (85%) IMCs compared to 7 of 18 (39%) non-IMCs ( P = 0.006). BCRP was expressed within emboli in 15 of 19 (79%) emboli in IMC, 12 of 15 (80%) primary IMCs, and 12 of 18 (67%) non-IMCs, without statistically significant differences ( P > .05). All IMCs and 67% of non-IMCs expressed at least 1 of the 2 transporters, and 63% (12/19) of IMCs and 39% (7/18) of non-IMCs expressed both P-gp and BCRP. P-gp and BCRP evaluation might help select patients for chemotherapy. P-gp, expressed in a significantly higher percentage of IMCs vs non-IMCs, might play a specific role in the chemoresistance of IMC.

The involvement of epidermal growth factor receptor (EGFR) is well established in human breast cancer, however, in canine mammary tumours (CMT), including inflammatory mammary carcinomas (IMC), still needs to be clarified. Enzyme immune assay techniques were used for EGFR determinations in tumour tissue from 45 bitches with CMT and in normal mammary glands from eight control dogs. Higher tissue EGFR levels were found in CMT compared with controls (P < 0.05). In malignant CMT, tissue EGFR elevated concentrations were statistically significantly associated with tumour relapse and/or distant metastasis during follow-up and with reduced disease-free and overall survival times. The IMC cases had the highest tissue EGFR levels compared with other malignant non-IMC tumours (P < 0.001). The results support the hypothesis that EGFR levels influence prognosis in malignant CMT, suggesting that EGFR may represent a therapeutic target in cases of high histological aggressiveness and especially in cases of metastatic phenotype and poor prognosis.

Background Treatment of adrenal-dependent hyperadrenocorticism (ADH) involves either surgical resection of the adrenal tumor or medical therapy. For many years, mitotane has been considered the medical treatment of choice for dogs with ADH. Objectives The aim of this study was to determine survival and prognostic factors for dogs with ADH treated with mitotane and trilostane. Animals Twenty-six dogs with ADH were included in the study. Methods Fourteen dogs were treated with mitotane and 12 dogs were treated with trilostane. Medical records were reviewed. Epidemiologic factors, signalment, clinicopathologic abnormalities, endocrine test results, and treatment protocols were evaluated to identify potential predictive factors of overall survival time. Results Survival times of dogs treated with mitotane (median, 15.6 months) or trilostane (median, 14.0 months) were not significantly different. Using univariate analysis, age and postadrenocorticotropic hormone cortisol concentrations were inversely correlated with survival time. The multivariate model also identified weakness at presentation as a negative prognostic indicator. Conclusion and Clinical Importance The type of medical treatment (mitotane versus trilostane) does not influence survival time in dogs with ADH; therefore, trilostane, a drug with less frequent and milder adverse effects, might be used as the primary medical treatment when adrenalectomy cannot be performed.

Background Trilostane is the drug of choice to treat pituitary-dependent hyperadrenocorticism (PDH) in dogs, but there is still controversy about which protocol best controls the clinical signs and results of adrenal functioning test. Objectives To compare the efficacy of twice daily (BID) versus once daily (SID) trilostane administration and to compare the safety of both protocols in the treatment of dogs with PDH. Animals Thirty-two client-owned dogs diagnosed with PDH between 2008 and 2010 and treated with trilostane either BID or SID. Methods In this prospective randomized study, 2 trilostane protocols were evaluated on the basis of the owner′s perception of clinical signs, on the results of laboratory tests, and on the results of the ACTH stimulation test in dogs with PDH. Dogs were followed up for a period of 1 year. Results During the study, more dogs in the BID group had complete clinical recovery than in the SID group. However, there was no significant difference in the mean post-ACTH cortisol concentration between groups. Basal cortisol concentration at 6 months was higher in animals treated SID compared with animals treated BID. Mean total daily doses of trilostane used to control PDH, as well as adverse effects observed in the course of the study, in both groups were not statistically different. Conclusion and Clinical Importance Adverse effects were mild using either protocol of treatment. Using trilostane BID might increase the number of dogs with a good clinical response compared with using trilostane SID.

Inflammatory mammary cancer (IMC) is a distinct form of mammary cancer that affects dogs and women [in humans, IMC is known as inflammatory breast cancer (IBC)], and is characterized by a sudden onset and an aggressive clinical course. Spontaneous canine IMC shares epidemiologic, histopathological and clinical characteristics with the disease in humans and has been proposed as the best spontaneous animal model for studying IBC, although several aspects remain unstudied. Interleukins (ILs) play an important role in cancer as potential modulators of angiogenesis, leukocyte infiltration and tumor growth. The aims of the present study were to assess serum and tumor levels of several ILs (IL-1α, IL-1β, IL-6, IL-8 and IL-10) by enzyme-immunoassay in dogs bearing benign and malignant mammary tumors, including dogs with IMC, for a better understanding of this disease. Forty-eight dogs were prospectively included. Animals consisted of 7 healthy Beagles used as donors for normal mammary glands (NMG) and serum controls (SCs), 10 dogs with hyperplasias and benign mammary tumors (HBMT), 24 with non-inflammatory malignant mammary tumors (non-IMC MMT) and 7 dogs with clinical and pathological IMC. IL-8 (serum) and IL-10 (serum and tissue homogenate) levels were higher in the dogs with IMC compared with the non-IMC MMT group. ILs were increased with tumor malignancy as follows: in tumor homogenates IL-6 levels were higher in malignant tumors (IMC and non-IMC MMT) versus HBMT and versus NMG and tumor IL-8 was increased in malignant tumors versus NMG; in serum, IL-1α and IL-8 levels were higher in the malignant groups respect to HBMT and SCs; interestingly, IL-10 was elevated only in the serum of IMC animals. To the best of our knowledge, this is the first report that analyzes ILs in IMC and IL-10 in canine mammary tumors. Our results indicate a role for IL-6, IL-8 and IL-10 in canine mammary malignancy and specific differences in ILs content in IMC versus non-IMC MMT that could have future diagnostic and therapeutic implications, to be confirmed in a larger series of IMC cases. These results help to support the validity of the IMC canine model for the study of human IBC and provide insight into this uncommon malignancy in dogs.

In this prospective study, a canine-adapted histological grading method was compared with histopathological and clinical characteristics and was evaluated as a prognostic indicator in canine mammary carcinomas (CMCs). Recruited dogs with at least 1 malignant mammary tumor ( n = 65) were clinically evaluated, surgically treated, and followed up (minimum follow-up 28 months, maximum 38 months). Histopathological diagnoses were performed according to Goldschmidt et al (2011). Tumors were graded as grade I (29/65), grade II (19/65), and grade III (17/65). The tumor size, clinical stage, histological diagnosis, presence/absence of myoepithelial proliferation, and regional lymph node metastases at diagnosis were significantly associated with histological grade. The histological grade, age, clinical stage, tumor subtype group, and lymph node metastases at time of diagnosis were significantly associated with the development of recurrences and/or metastases, cancer-associated death, and survival times (disease-free survival and overall survival) in univariate analyses. A subdivision of clinical stage I (T1N0M0) into stages IA and IB was proposed in terms of prognosis. The clinical stage, histological grade, and spay status were selected as independent prognostic variables (multivariate analyses) with disease-free survival as the dependent variable. When overall survival was evaluated as a dependent variable, clinical stage and histological grade were selected as the independent covariates. This grading system is a useful prognostic tool, facilitates histological interpretation, and offers uniform criteria for veterinary pathologists. Comparative studies on CMCs performed in different countries should take into account possible changes in the prognoses due to different proportions of spayed females among the selected dog population.

Inflammatory mammary cancer (IMC) is the most aggressive and lethal type of mammary cancer in women and dogs. The aim of this study was to determine whether the pattern of metastasis for canine IMC differed from that for canine non-inflammatory malignant mammary tumours (NIMMTs). Samples from a total of 72 intact female dogs were evaluated in the study. Thirty-nine of these dogs had IMC and 33 had NIMMTs. Different patterns of metastasis were observed between the groups. Metastases to the urinary bladder and reproductive tract were found only in dogs with IMC. In contrast, IMC never metastasized to the bone and there was less frequent metastasis to the lungs, liver and kidney. This metastatic pattern in IMC supports the hypothesis that this form of mammary neoplasia has a distinct pathogenesis. These data have clinical relevance and the observations may have value in consideration of the fact that canine IMC has been proposed as a natural model for the study of human inflammatory breast cancer.

Introduction: Multidrug resistance of neoplastic cells is frequently related to the expression of P-glycoprotein (PGP) and breast cancer resistance protein (BCRP). Canine inflammatory mammary carcinoma (IC) and grade 3 carcinoma (C3) are biologically aggressive and they could benefit from chemotherapy. Our study describes the expression of PGP and BCRP in these tumours. Materials and Methods: Samples included 18 C3s and 20 ICs from dogs that had not received chemotherapy before biopsy. Primary carcinoma was identified in 15 cases of IC. Tumours were classified into histological subtypes. IHC for PGP and BCRP was considered positive when O20% and O10% of cells were labelled for PGP and BCRP, respectively. Results: Immunolabelling was mainly membranous for PGP, showing a strong reaction in emboli, while membranous and cytoplasmic labelling was mainly seen for BCRP. PGP was highly expressed in the different tumours, but was significantly higher in emboli of IC versus C3 (PGP P 5 0.006) and in primary IC versus C3 (PGP P 5 0.032). There was no significant difference in BCRP expression between groups, being expressed in 78.95% of emboli of CI, 80% of primary IC and 66.67% of C3. Conclusions: Chemoresistance is a phenomenon present in dogs with C3 and IC. Our results indicate the need for a combined therapy rather than chemotherapy alone. The high expression of PGP in ICs compared with non-inflammatory mammary carcinomas is an interesting finding that can explain a higher resistance to chemotherapy in this type of cancer and could be related to the specific pathogenic mechanisms that this disease exhibits.

Canine inflammatory mammary cancer (IMC) and human inflammatory breast cancer (IBC) are the most aggressive and lethal type of mammary cancer in female dogs and in women. The generation of microvascular channels by malignant tumor cells (endothelial-like cells [ELCs]) without endothelial cell participation (vasculogenic mimicry) has been reported in human breast cancer, including IBC, and is considered a new type of tumor angiogenesis. The aim of this study was to investigate the presence of ELCs in highly malignant canine mammary tumors (IMC and non-IMC) by histology, inmunohistochemistry (pancytokeratin, cytokeratin 14, vimentin, actin, desmin, vWF, CD31, and CD34), and electron microscopy. This retrospective study included 21 female dogs with diagnoses of IMC and 20 animals with metastatic grade III noninflammatory malignant mammary tumors (MMT). IMC tumors (33.33%) and MMT (5%) showed ELCs forming structures similar to small capillaries. The histological, immunohistochemical (positive to AE1/AE3 and cytokeratin 14, mostly negative to endothelial markers), and ultrastructural characteristics of these cells indicated vasculogenic mimicry. The higher frequency of this phenomenon in inflammatory versus noninflammatory canine mammary cancer is in agreement with previous studies in experimental and spontaneous human IBC, and it could be in relation with the extremely high lymphangiogenic capacity and metastatic lymphangiotropism characteristics of inflammatory breast cancer.

Growth hormone (GH), insulin-like growth factor I (IGF-I), progesterone (P4) and 17beta-estradiol (17-E2) concentrations have been studied in 84 mammary tumours (44 dysplasias and benign tumours and 40 malignant neoplasias) from 33 female dogs. Thirteen normal mammary glands from 80 healthy female dogs were also analysed as controls. GH concentrations were determined in mammary homogenates by radio-immunoassay. IGF-I, P4 and 17-E2 tissue levels were determined by enzyme-immunoassay (EIA) techniques. The potential correlations between GH/IGF-I concentrations and P4 and 17-E2 mammary tissue levels were investigated. Tissue GH (p0.01) and IGF-I concentrations (p0.01) were significantly higher in malignant tumours than in benign neoplasms. Likewise, malignant tumours were the mammary lesions that displayed the highest P4 and 17-E2 tissue levels. Strong correlations between GH/IGF-I (n=84; r=0.436; p0.001), P4/GH (n=84; r=0.562; p0.001) and 17-E2/IGF-I (n=84; r=0.638; p0.001) were observed in tumoral tissue homogenates. Our study provides evidence that P4 might increase autocrine GH production which might directly stimulate local or systemic IGF-I secretion. Additionally, the IGF-I effect might be influenced by local levels of 17-E2. These results suggest that all these hormones and factors might act as local growth factors stimulating the development and/or maintenance of canine mammary tumours in an autocrine/paracrine manner.

Summary Chronic ingestion of bracken fern (Pteridium spp.) by cattle produces upper alimentary tract and urinary bladder tumours causing a syndrome called bovine enzootic haematuria (BEH). Previous studies demonstrated ptaquiloside–DNA adducts and mutations in the h-ras gene in ileal epithelial cells of bracken fern-fed calves. Systematic inspection of the bladder mucosa of grazing cattle (nZ126) from bracken-fern areas was carried out in a slaughterhouse. Of the 126 slaughterhouse cattle, 46 showed macroscopical lesions of the bladder. These bladders, together with six others known to have BEH, were examined histopathologically and by H-ras immunohistochemistry. Thirteen affected bladders were also examined by H-ras molecular analysis to detect mutations. Macroscopical and histological study of urinary bladder lesions found at the slaughterhouse revealed chronic cystitis (34.1%) and tumours (2.4%). There was significantly increased immunohistochemical expression of H-ras (P!0.05) in chronic cystitis (H-rasZ53.24%) and bladder tumours (H-rasZ63.60%) as compared with normal urinary bladders (H-rasZ4.32%). A silent mutation (D38D) was detected in one animal with a mixed bladder tumour. The prevalence of urinary bladder lesions (chronic cystitis and tumours) obtained at the slaughterhouse was higher than expected. This study demonstrates that close inspection of urinary bladders of adult grazing cows is necessary to prevent possible human exposure to bracken-fern carcinogens. The absence of mutations in the codons of h-ras studied did not exclude the presence of polymorphisms in other regions of the gene (promoter or regulation sequences) or in other genes (belonging or not to the ras family) that significantly affect the H-ras protein. q 2004 Elsevier Ltd. All rights reserved.

The biological implications of serum and tissue prolactin levels in canine mammary tumours (CMT) have been previously described although the influence of this hormone on inflammatory mammary carcinomas as well as its value as prognostic indicator remains to be properly clarified. Prolactin determinations were carried out by enzyme immunoassay in tumour tissue and serum of 39 female dogs with spontaneous CMT and in normal mammary gland and serum of 10 controls. Prolactin levels were higher in the case of CMT compared to controls (P

Eighty-nine canine mammary tumors and dysplasias of 66 bitches were investigated to determine the immunohistochemical expression of classical estrogen receptor (ER-α) and its clinical and pathologic associations and prognostic value. A complete clinical examination was performed and reproductive history was evaluated. After surgery, all animals were followed-up for 18 months, with clinical examinations every 3–4 months. ER-α expression was higher in tumors of genitally intact and young bitches ( P < 0.01, P < 0.01) and in animals with regular estrous periods ( P = 0.03). Malignant tumors of the bitches with a previous clinical history of pseudopregnancy expressed significantly more ER-α ( P = 0.04). Immunoexpression of ER-α decreased significantly with tumor size ( P = 0.05) and skin ulceration ( P = 0.01). Low levels of ER-α were significantly associated with lymph node involvement ( P < 0.01). Malignant tumors had lower ER-α expression than did benign tumors ( P < 0.01). Proliferation index measured by proliferating cell nuclear antigen immunostaining was inversely correlated with ER-α scores ( P = 0.05) in all tumors. Low ER-α levels in primary malignant tumors were significantly associated with the occurrence of metastases in the follow-up ( P = 0.03). Multivariate analyses were performed to determine the prognostic significance of some follow-up variables. ER-α value, Ki-67 index, and age were independent factors that could predict disease-free survival. Lymph node status, age, and ER-α index were independent prognostic factors for the overall survival. The immunohistochemical detection of ER-α in canine mammary tumors is a simple technique with prognostic value that could be useful in selecting appropriate hormonal therapy.

Cyclooxygenase-2 (Cox-2) enzyme participates in different steps of the carcinogenetic process and in canine mammary tumours (CMTs), a high expression of Cox-2 is associated with malignancy and tumour angiogenesis. The objectives of the study were to evaluate the disease-free survival (DFS) and overall survival (OS) of a Cox-2 inhibitor as adjuvant therapy in dogs with highly malignant (HM)-CMTs and compare it with that of dogs treated with chemotherapy and with control dogs. Twenty-eight dogs were prospectively included. After surgery, dogs were alternatively allocated into two treatment groups (chemotherapy with mitoxantrone n=8; Cox-2 inhibitor, firocoxib n=7). Control group (n=13) included dogs whose owners rejected adjuvant therapy. All dogs were followed up for two years or until death. The DFS was significantly higher in dogs that received adjuvant treatment (mitoxantrone or firocoxib) (P=0.030) than in control dogs. Dogs on firocoxib treatment had significantly higher DFS (P=0.015) and OS (P=0.048) than control dogs. The DFS and OS of dogs on mitoxantrone treatment were not statistically different from controls. In conclusion, this study supports the use of firocoxib for the treatment of HM-CMTs. Further studies are needed to compare the efficacy of chemotherapy drugs versus Cox-2 inhibitors as adjuvant treatment in these cases.

Seven of 30 female dogs diagnosed with inflammatory mammary cancer were given chemotherapy and palliative treatment, and the other 23 received only palliative treatment. The median survival time of the seven dogs given chemotherapy was 57 days, compared with 35 days for the 23 given only palliative treatment.

The aims of this study were to investigate the serum and tissue content of androgens and estrogens in canine inflammatory mammary carcinomas (IMC) as well as in non-inflammatory malignant mammary tumors (MMT), and assessed the immunoexpression of estrogen and androgen receptors using immunohistochemistry. Profiles for the androgens dehydroepiandrosterone (DHEA), androstenedione (A4), and testosterone (T), and for the estrogens 17beta estradiol (E2) and estrone-sulphate (SO4E1) were measured both in tissue homogenates and in serum of MMT and IMC by EIA techniques in 42 non-inflammatory malignant mammary tumors (MMT) and in 14 inflammatory mammary carcinomas (IMC), prospectively collected from 56 female dogs. Androgen receptor (AR) and estrogen receptor alpha (ERalpha) and beta (ERbeta) expression was studied using immunohistochemistry (strepavidin-biotin-peroxidase method) in samples of 32 MMT and 14 IMC, and counted by a computer image analyzer. IMC serum and tissue levels of androgens were significantly higher than MMT levels. Tissue content of estrogens was also significantly higher in IMC than in MMT. Serum values of SO4E1 were significantly higher in IMC, but serum levels of E2 were significantly lower in IMC compared to MMT cases. Medium-high androgen receptor intensity was observed in 64.28% of IMC and 40.62% of MMT. No important differences were found between ERalpha expression in IMC (100% negative) and MMT (90% negative). ERbeta and AR were intensely expressed in highly malignant inflammatory mammary carcinoma cells. To our knowledge, this is the first report relative to AR immunohistochemistry in canine mammary cancer and to estrogens or androgens in serum of dogs with benign or malignant mammary tumors.

In several animal studies, prolactin has been found to be essential for mammary epithelial development, and its administration has been consistently shown to increase the rate of mammary tumours. High levels of steroid hormones have also been suggested to enhance mammary cancer development. The present study investigates the levels of the following hormones in serum and in tissue homogenates in dogs bearing canine mammary tumours: prolactin (PRL), progesterone (P4), dehydroepiandrosterone (DHEA), androstenedione (A4), testosterone (T), 17beta-estradiol (17beta-E2) and estrone sulfate (S04E1). Eighty mammary tumours (40 dysplasias and benign and 40 malignant tumours) from 32 female dogs, and 10 normal mammary glands from eight female dogs without history of mammary tumours, were analysed. Prolactin and steroid hormones in serum and tissue homogenates, were analysed by enzyme immunoassays (EIA) techniques, previously validated for this animal species. Levels of prolactin in tissue homogenates were significantly different between malignant and benign mammary tumours (p

BRCA1 is a nuclear phosphoprotein that participates in the regulation of the cell cycle. The role of the BRCA1 gene in canine mammary tissue and mammary tumours has not been studied. The present study examined immunohistochemically the expression and intracellular distribution of BRCA1 protein in two normal, seven dysplastic and 44 neoplastic canine mammary glands and its relationship with clinical and pathological variables and other prognostic parameters. Strong nuclear immunolabelling of BRCA1 protein was observed in the epithelial cells of the normal mammary glands and mammary dysplasias. The majority of benign tumours, and more especially of malignant tumours, showed a significant reduction in the nuclear expression of BRCA1 protein and an increase in cytoplasmic expression. Loss of BRCA1 expression was associated with high proliferation marker Ki-67 and ER-alpha negative tumours. The reduction and aberrant distribution of BRCA1 in canine mammary tumours were significantly associated with malignant characteristics. The results may indicate that BRCA1 has a role in the malignant behaviour of these tumours.

Inflammatory mammary carcinoma (IMC) is the most aggressive spontaneous type of mammary malignant tumor both in women and dogs. Latest studies in dogs indicate that different endocrine mechanisms seem to be involved in inflammatory carcinomas (IMCs). The aim of the present study was to characterize the steroid hormone profile of inflammatory carcinoma, and to compare it with mammary dysplasias, benign tumors and other malignant tumors. Eighty-six mammary samples (10 normal mammary tissue, 21 dysplasias, 26 benign, 22 malignant, and 7 IMC) from 30 female dogs were used. Hormone levels of progesterone (P4), 17beta-estradiol (E2), androstenedione (A4), dehydroepiandrosterone (DHEA), and estrone sulphate (E1SO4) in tissue homogenates were measured by enzyme immunoassays (EIAs) techniques, previously validated for this species. IMC displayed the following steroid profile: P4: 13.80+/-0.56 microg/g; E2: 675.19+/-33.00 ng/g; A4: 631.73+/-70.73 microg/g; DHEA: 702.22+/-89.93 microg/g, and E1SO4: 2.84+/-0.32 mg/g. All of these hormones were significantly higher (P