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Background: Gonadoblastoma (GB) is a rare mixed germ cell-sex cord-stromal tumour, first described in humans, commonly found in dysgenetic gonads of intersex patients that have a Y chromosome. However, this entity in not recognized in the WHO classification of tumours of genital system of domestic animals. Herein, we describe a case of ovarian gonadoblastoma with proliferation of dysgerminoma and sex cord-stromal tumour components, in a phenotypically and cytogenetically normal bitch. Case presentation: A 17-year-old cross-breed bitch had a firm, grey-white multinodular mass in the left ovary. The tumour was submitted to histopathological examination and Y chromosome detected through karyotype analysis and PCR studies. Microscopically, the ovary was almost replaced by an irregular neoplasm composed of three distinct, intermixed elements: dysgerminoma, mixed germ cell-sex cord-stromal tumour resembling human GB and a proliferative sex cord-stromal tumour component. The germ cells of gonadoblastoma and dysgerminoma components were immunoreactive for c-KIT. Sex cord-stromal cells of gonadoblastoma were immunoreactive for a-inhibin. The sex cord-stromal tumour was immunoreactive for AE1/AE3, occasionally for a-inhibin and negative for epithelial membrane antigen (EMA). The karyotype was 78, XX and PCR analysis confirmed the absence of the Y chromosome. Conclusion: Based on these findings, a diagnosis of gonadoblastoma with proliferation of dysgerminoma and sex cord-stromal tumour was made. This is the first case of ovarian gonadoblastoma in a female dog. Ana R. Flores (SFRH/BD/116373/2016) and João Lobo (SFRH/BD/132751/2017) acknowledge FCT, the Portuguese Foundation for Science and Technology, for financial support. IPATIMUP integrates the i3S Research Unit, which is partially supported by FEDER through the Operational Programme for Competitiveness Factors-COMPETE and National Funds through the Portuguese Foundation for Science and Technology (FCT), under the project number PEst-C/SAU/LA0003/2013. We kindly thank Professor Beatriz Porto and Mrs. Cláudia Oliveira from laboratory of Cytogenetics of the ICBAS-UP for the karyotype analysis and Msc. Patrícia Barradas who provided PCR technical support. We would like to thank Paulo Flores for help with scientific illustration.

TFF1 expression is markedly reduced in human GCs, suggesting that TFF1 is a tumor suppressor for human gastric cancer. The present study evaluated the expression and distribution pattern of TFF1 in paraffin-embedded canine gastric tissue samples, including normal mucosa (n = 3), polyps (n = 8), carcinomas (n = 31) and their adjacent non-neoplastic mucosa (n = 30), neoplastic emboli (n = 14), and metastatic lesions (n = 9), by immunohistochemistry (IHC). All normal gastric tissues expressed TFF1 in the superficial foveolar epithelium and mucopeptic cells of the neck region. Most gastric polyps (GPs) displayed immunoreactivity for TFF1 in &gt, 75% of the epithelial component. In GCs, the expression of TFF1 was found reduced in 74.2% of the cases. The level of TFF1 expression had a decreased tendency from normal gastric mucosa to GPs and GCs (p &lt, 0.05). No significant differences in the expression of TFF1 were found in GCs, according to age, sex, histological type based on World Health Organization (WHO) and Lauren classification, tumor location, depth of tumor invasion, presence of neoplastic emboli or metastatic lesions. The median survival time of GC patients with preserved and reduced TFF1 immunoexpression were 30 and 12 days, respectively. Kaplan–Meier analysis revealed no significant survival differences between the two groups (p &gt, 0.05). These findings suggest that TFF1 protein may play a role in canine gastric carcinogenesis, and further studies are necessary to define its usefulness as a prognostic indicator in canine gastric carcinoma.

Background Ovine pulmonary adenocarcinoma (OPA) is a neoplastic disease caused by exogenous Jaagsiekte Sheep Retrovirus (exJSRV). The prevalence of JSRV-related OPA in Eastern European countries, including Romania is unknown. We aimed to investigate: the prevalence and morphological features of OPA (classical and atypical forms) in the Transylvania region (Romania), the immunophenotype of the pulmonary tumors and their relationships with exJSRV infection. A total of 2693 adult ewes slaughtered between 2017 and 2019 in two private slaughterhouses from Transylvania region (Romania) was evaluated. Lung tumors were subsequently assessed by cytology, histology, immunocytochemistry, immunohistochemistry, electron microscopy and DNA testing. Results Out of 2693 examined sheep, 34 had OPA (1.26% prevalence). The diaphragmatic lobes were the most affected. Grossly, the classical OPA was identified in 88.24% of investigated cases and the atypical OPA in 11.76% that included solitary myxomatous nodules. Histopathology results confirmed the presence of OPA in all suspected cases, which were classified into acinar and papillary types. Myxoid growths (MGs) were diagnosed in 6 classical OPA cases and in 2 cases of atypical form. Lung adenocarcinoma was positive for MCK and TTF-1, and MGs showed immunoreaction for Vimentin, Desmin and SMA; Ki67 expression of classical OPA was higher than atypical OPA and MGs. JSRV-MA was identified by IHC (94.11%) in both epithelial and mesenchymal cells of OPA. Immunocytochemistry and electron microscopy also confirmed the JSRV within the neoplastic cells. ExJSRV was identified by PCR in 97.05% of analyzed samples. Phylogenetic analysis revealed the presence of the exJSRV type 2 (MT809678.1) in Romanian sheep affected by lung cancer and showed a high similarity with the UK strain (AF105220.1). Conclusions In this study, we confirmed for the first time in Romania the presence of exJSRV in naturally occurring OPA in sheep. Additionally, we described the first report of atypical OPA in Romania, and to the best of our knowledge, in Eastern Europe. Finally, we showed that MGs have a myofibroblastic origin.

Malignant transformation is often associated with abnormal protein glycosylation expressed, amongst others, by the accumulation of simple mucin-type carbohydrates namely Tn and Sialyl-Tn (STn) antigens. These are usually limited in normal tissues and their increased expression has been associated with cancer progression and poor prognosis. This study aims to evaluate the role of Tn and STn antigens in the neoplastic transformation of the canine gastric mucosa and to correlate their putative immunoexpression alterations with some pathological features. Tn and STn antigens expression were immunohistochemically evaluated in canine normal gastric mucosa (n = 3), gastric polyps (n = 9) and gastric carcinomas (n = 25), neoplastic emboli (n = 12) and metastases (n = 8). In normal gastric mucosa, Tn antigen was detected in the gastric epithelial cells, while STn antigen was absent. Similarly, all gastric polyps expressed Tn antigen, but none displayed STn antigen immunostaining. In carcinomas, Tn antigen was expressed in 96% of the cases and STn antigen in 68% of the neoplasms. STn antigen was significantly higher in carcinomas compared with normal mucosa (P < .05). No correlation was found between each antigen and the different subtypes of tumours according to WHO classification, tumour differentiation, lymph vascular invasion or metastasis. All neoplastic emboli expressed both antigens, and the expression score was similar or higher than that displayed by the neoplastic cells of the primary tumour. The high prevalence of STn antigen in gastric carcinomas compared with normal mucosa highlights the cancer-associated nature of this antigen. Our results link STn antigen expression to neoplastic transformation and suggest that it may be a useful marker of gastric cancer progression in dogs.

A 12-year-old neutered female mixed-breed dog was referred for occasional vomiting that had increased progressively in frequency over the past 3 months. Palpation of the abdomen revealed a firm mass of unknown aetiology, located within the cranial to mid abdomen, while abdominal surgical exploration revealed a well-defined abdominal mass of pancreatic origin. The pancreatic mass caused lateral displacement of the duodenum as well as medial displacement of the pylorus, resulting in impairment of pyloric outflow. Further examination revealed a firm, poorly vascularized and coarsely lobulated structure. The histopathological findings were consistent with severe pancreatic lipomatosis and atrophy. Immunohistochemically, the remnant pancreatic cells were positive for cytokeratins AE1/AE3 and glucagon, and negative for insulin. Routine follow-up with the referring veterinarian showed no evidence of postoperative complications, but the dog continued to deteriorate further and died despite medical management. Pancreatic lipomatosis is a rare condition in small animal practice. The aetiology or predisposing factors have not been identified in animals.

Cyclooxygenase-2 (COX-2) is overexpressed in several human and animal neoplasms, including the human endometrial carcinoma. It has been suggested as a prognostic marker and a potential therapeutic target. This study aimed to (i) clarify histological aspects of feline endometrial adenocarcinomas (FEA) of the papillary serous type and (ii) characterize COX-2 immunohistochemical expression in normal, hyperplastic and neoplastic endometrium in this species. Archived paraffin-embedded tissue samples of 33 FEA, eight cystic endometrial hyperplasias (CEHs) and 21 samples of normal, healthy endometrium in the follicular (FS; n = 10) and luteal (LS; n = 11) stages were evaluated. Histological evaluation of haematoxylin and eosin-stained sections of the FEA revealed a papillary proliferation of neoplastic cells of serous type, accompanied by clear and multinucleated cells. Other architectural arrangements mainly included solid and tubular growth. Randomly distributed areas of necrosis within the tumours were commonly observed. Invasion of the myometrium, of the serosa and of the vascular and/or lymphatic vessels was not constant features. The mean number of mitoses was higher in FEA compared to non-neoplastic endometrium. COX-2 scores were lower in FEA (p = 0.003) and CEH (p = 0.05) when compared to normal epithelium (NE). The loss of the membrane apical reinforcement in epithelial cells was observed in FEA samples, which was accompanied by the dislocation of COX-2 labelling into the cytoplasm and the perinuclear area; in contrast, in epithelial cells in the healthy and hyperplastic endometria, the immunoreaction showed the characteristic pattern of apical membrane reinforcement, suggestive of the membrane polarization. COX-2 epithelial scores were higher in the FS than in the LS. No differences were found in stromal COX-2 expression between normal, CEH and FEA groups, but it was higher in the LS than in the FS. In summary, loss of COX-2 compartmentalization in neoplastic epithelial cells might be one of the molecular events underlying endometrial carcinogenesis.

Made available in DSpace on 2018-12-11T17:18:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-12-01. Added 1 bitstream(s) on 2019-10-09T18:31:33Z : No. of bitstreams: 1 S0100-736X2017001201519.pdf: 3105779 bytes, checksum: e7e2b1d54005cd3be7ef11220dbb4333 (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Histochemical staining consists of a set of specific chemical reactions of structures or tissue-endogenous substances. Immunohistochemistry allows verification of proteins in tissues related to biological and pathological factors. The standardization of methods to assess angiogenesis resulting from formation of new blood vessels in procedures with stimulants is important to facilitate the implementation of research as well as to assist interpretation of data. In rabbits some markers of angiogenesis antibodies in the skin are not standardized because of cross-reactions that may occur because the antibodies are made from such animals.The aim of this study was to analyze the immunohistochemical methods through dyes and immunohistochemical markers angiogenesis in rabbits (Oryctolagus cuniculus) having undergone reconstructive surgery with skin grafts associated with plasma angiogenesis stimulator rich in platelets, in order to evaluate which method would be better to visualize the vessels, as well as to evaluate which antibody would promote better immunostaining, and find the differences between the methods and to standardize the methodology to be applied in experiments using rabbits. Sixteen rabbits were used, split into two groups of eight animals: Gprp (plasma rich in platelets) and Gc (control, saline solution, 9%). The same technique of reconstructive surgery using graft mesh was performed on each rabbit. The groups differed only in the application of platelet-rich plasma before the surgical wound synthesis. Samples for evaluation of angiogenesis were collected 15 days after the surgical procedure. The dyes Hematoxylin & Eosin and Masson's Trichrome were used in the histochemical study to evaluate vascular proliferation. Markers CD31, CD34 and Caveolin-1 was used for the immunohistochemical study. The evaluation between the groups (Gprp and Gc) in regard to the categorical variable (vascular proliferation intensity) used the Kruskal-Wallis test with p values equal to or less than 0.05 being considered significant. The immunohistochemistry was subjected to analysis of variance for a completely randomized design, with two groups and five repetitions (medium) and 5% significance level. Multiple comparison of groups resulted in the Tukey test (p=0.05) used. The amount of vascular proliferation assessed by histochemical method HE and Masson's Trichrome was found to be a significant variable in Gprp when compared with group Gc. When evaluating the methods used, there was no significant difference. There was no difference in the three markers which were used for correlating microvessels; however, there was more intense staining of vessels when Caveolin-1 Antibody was used. This caused intense marking of the capillaries and small vessels, as well as of larger vessels. When using CD31 and CD34, the same was observed, but it was not as intense as with Caveolin-1; though some cases showed sincere and discreet marking. The results of this study demonstrated that the histochemical methods performed are effective for semi-quantitative assessment of angiogenesis. The immunohistochemical comparison of Caveolin-1, CD31, and CD34 as markers of angiogenesis in rabbits showed that both antibodies could immunostain the newly formed vessels; but the Caveolin-1 showed better immunostaining in small and medium-sized vessels, as well as a minor presence in the background. Although not specific markers for angiogenesis, they can be used as immunohistochemical markers of vascular endothelium in rabbits. Departamento de Clínica e Cirurgia Veterinária Faculdade de Ciências Agrárias e Veterinárias (FCAV) Universidade Estadual Paulista (Unesp), Via de Acesso Professor Paulo Donato Castellane s/n Departamento de Patologia Veterinária Instituto de Ciências Biomédicas Abel Salazar (ICBAS) Universidade do Porto (UP), Rua Jorge Viterbo Ferreira 228 Departamento de Clínica e Cirurgia Veterinária Faculdade de Ciências Agrárias e Veterinárias (FCAV) Universidade Estadual Paulista (Unesp), Via de Acesso Professor Paulo Donato Castellane s/n

Claudins (CLDNs) are tight junction proteins that have a role in regulating cell adhesion and polarity, paracellular permeability, proliferation and differentiation. Several immunohistochemical studies have shown reduced expression of CLDN-1 and CLDN-7 in human and canine mammary carcinomas, suggesting that these proteins may participate in mammary carcinogenesis, invasion and metastasis. The present study characterizes expression of CLDN-1 and CLDN-7 in feline mammary carcinomas (n = 52) and their metastases (n = 29). There was an inverse association between CLDN-7 expression and histological grade of tumour. Reduced expression of CLDN-7 was significantly associated with decreased tubule formation, high proliferative activity and metastasis. No significant associations were found between CLDN-1 expression and any of these features. Evaluation of expression of CLDN-7, but not CLDN-1, may therefore provide prognostic information, assisting in the diagnosis of a subgroup of aggressive feline mammary carcinomas that share some features with the recently described 'claudin-low' subgroup of human breast cancer.

Claudins (CLDNs) are a family of tight junction (TJ) proteins that play an important role in maintaining cell polarity, in controlling paracellular ion flux and in regulating cell proliferation and differentiation. There is a growing body of evidence that associates changes in CLDN expression with the development of human breast cancer. In the present study CLDN-2 expression was examined immunohistochemically in samples of normal feline mammary tissue (n = 5) and mammary carcinomas (n = 52), including metastatic lesions (n = 29). Seventy-seven percent of carcinomas showed reduced CLDN-2 expression compared with that observed in normal mammary gland. Reduced expression of CLDN-2 was significantly associated with a high histological grade of carcinoma (P = 0.011), with 88.6% of grade II/III carcinomas showing decreased expression. Furthermore, CLDN-2 down-regulation was significantly associated with metastatic disease (P = 0.0027), with 93.1% of cases with signs of metastasis showing decreased expression of this protein. CLDN-2 may constitute a molecular marker for identification of a subgroup of feline mammary carcinomas characterized by high histological grade and the development of metastasis.

E-cadherin and beta-catenin are component of adherens junctions in epithelial cells. Loss of these proteins have been associated with progression of prostatic diseases. We performed immunohistochemistry for E-cadherin, beta-catenin and Ki-67 on canine prostatic lesions. We analyzed the expression of these antibodies in benign prostatic hyperplasia (BPH, n = 22), in pre neoplastic lesions Prostatic Intra-epithelial Neoplasia (PIN), n = 3 and Prostatic Inflammatory Atrophy (PIA), n = 7 and prostate carcinoma (PC, n = 10). In this study, a membranous expression of E-cadherin and beta-catenin and nuclear expression of Ki-67 antigen were demonstrated. The proliferative index was statistically different between carcinomas and BPH and carcinomas and pre-neoplastic lesions. Like in men, the reduction of E-cadherin and increase of Ki-67 expression in neoplastic lesions in dog prostate may be related to the carcinogenic process in this gland.

BACKGROUND/AIM Peripheral nerve sheath tumors (PNSTs) belong to a very heterogeneous group of neoplasms occurring both in dogs and humans. The aim of the present study was to evaluate the histological and immunohistochemical features of canine cutaneous PNSTs contributing to further refine their diagnosis. MATERIALS AND METHODS The histopathological phenotype and biological behavior of 40 canine cutaneous PNSTs were evaluated and vimentin, S-100, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), desmin, alpha-smooth muscle actin (α-SMA) and Ki-67 immunoreactivity were assessed. RESULTS Respectively, 17 and 23 lesions were classified as benign and malignant PNSTs. The malignant lesions were more often positive for S-100 and presented a proliferation index significantly higher when compared to the benign ones (p

Background Endometrial adenocarcinomas are a rare type of tumour in cats. Though different morphologies have been reported, the most frequent histological type of feline endometrial adenocarcinoma (FEA) is the papillary serous. Characterization of molecular markers expression in FEA may contribute to clarify the pathogenesis of these tumours and to assess the differences between normal endometrium and FEA regarding the expression pattern of several proteins. Therefore, this study aimed to evaluate the immunohistochemical profile of a wide panel of antibodies (specific for ER-α, PR, Ki-67, CK7 and CK20) in twenty-four cases of FEA. Comparisons were made between FEA and feline normal cyclic endometrium in follicular (n = 13) and luteal (n = 10) stages. Except for Ki-67, all other molecular markers were assessed independently for the intensity of immunolabeling and for the percentage of cells expressing the protein. Results This study showed that in FEA a loss of expression occurs for ER-α (P ≤ 0.0001) and less markedly also for PR. The lost in sex steroid receptors concerns a decrease in both the proportion of labelled cells and the intensity of immunolabelling (P = 0.002 and P = 0.024, respectively). Proliferative activity, estimated via Ki-67 immunoreaction, significantly increased in FEA as compared to normal endometrium (P ≤ 0.0001). Feline endometrial adenocarcinomas maintained the CK7+/CK20+ status of normal endometrium. However, FEA showed decreased CK7 intensity of labelling compared to normal endometria (P ≤ 0.0001) and loss of CK20 expression, both in intensity (P ≤ 0.0001) and in percentage of positive cells (P = 0.01), compared to normal tissues. Conclusions Data gathered in this study suggest that proliferation in FEA accompanies ER-α down-regulation, possibly following activation of pathways mediated by local growth factors. Moreover, FEA retains combined expression of CK7 and CK20, as evidenced in normal endometrial epithelia, although a decrease in CK7 expression was observed.

The authors describe their experience with an automated immunohistochemical system applied to canine tissue samples. Twenty human cellular markers specific monoclonal and polyclonal antibodies and two different antigen retrieval methods were used in normal and neoplastic breast tissue, as well as skin samples obtained from female dogs of pure and mixed breeds. The antibodies tested were the most frequently used in human and veterinary medicine studies, employed with diagnostic purposes in breast pathology, as well as in cancer research. Most of them may be used to study other normal and abnormal tissues and included cytokeratins, progesterone receptor, c-erbB2, p53, MIB-1, PCNA, EMA, vimentin, desmin, alpha-actin, S-100, pan-cadherin, and E-cadherin. The results demonstrated that using an automated staining system it is possible to use different human markers in veterinary pathology. The advantages of automated immunohistochemistry are improved quality, reproducibility, speed, and standardisation. Os autores descrevem sua experiência com um sistema automático de imunoistoquímica aplicada à amostras de tecido canino. Foram utilizados 20 anticorpos humanos monoclonais e policlonais e dois diferentes métodos de recuperação antigênica em tecido mamário normal e neoplásico, bem como em amostras de pele obtidas de cadelas. Os anticorpos testados estão entre os mais usados em estudos de medicina humana e veterinária, com finalidade de diagnóstico em patologia mamária, bem como na pesquisa do câncer. Muitos deles podem ser usados para estudar outros tecidos normais e com alterações e incluem citoqueratinas, receptor de progesterona, c-erbB2, p53, MIB-1, PCNA, EMA, vimentina, desmina, alfa-actina, S-100, pan-caderina e E-caderina. Os resultados demonstraram que usando um sistema automático de imunoistoquímica é possível usar diferentes marcadores humanos em patologia veterinária. As vantagens da imunoistoquímica automatizada são melhora da qualidade, reprodutibilidade, rapidez e padronização.

DNA measurement by image cytometry, and a detailed immunohistochemical study using monoclonal antibodies directed against different human cytokeratin types, muscle-specific actin, vimentin and S100 protein were carried out on normal canine mammary tissue (n =4), benign canine mammary mixed tumours (n =20) and malignant canine mammary mixed tumours (n =13). The results showed that ductal and alveolar luminal cells in normal and neoplastic tissue were immunoreactive with CAM5.2 and AE1/AE3 antibodies recognizing human keratins.Basal/myoepithelial cells were clearly differentiated from ductal and alveolar epithelial cells, since the latter only expressed cytokeratins, whereas the former also expressed vimentin and muscle-specific actin. This immunohistochemical study showed that there is loss of expression of muscle-specific actin and cytokeratins in areas of myoepithelial proliferation, and enhanced expression of vimentin and S100 protein in proliferative areas with osseous and/or chondroid metaplasia. The ploidy studies revealed that 20% (4/20) of benign and 54% (7/13) of malignant mixed tumours of canine mammary gland were aneuploid and that the epithelial and myoepithelial components of the mixed tumours had identical DNA content. Our results reinforce the role of myoepithelial cells in mesenchymal metaplasia in mixed mammary tumours and suggest the possibility of a common origin of both components from a totipotential stem cell with capacity for divergent differentiation.

Background Gastric polyps (GP) are characterised by luminal overgrowths projecting above the plane of the mucosal surface that can be classified as non-neoplastic and neoplastic lesions. In humans, recent studies have drawn attention to the malignant potential of some of these lesions. However, gastric polyps are uncommon lesions in dogs. Findings In this study, the presence of Helicobacter spp., the cellular proliferative activity, potential phenotypic alterations, COX-2 and p53 expression in canine spontaneous gastric polyps were investigated. The expression of these molecules was also studied in normal canine gastric mucosa in order to gain further knowledge of the significance of their loss or overexpression in gastric lesions. Conclusions The normal expression of almost all the factors evaluated, along with the reduced proliferative activity is strongly suggestive that, in dogs, spontaneous gastric polyps are not only a rare finding but also of benign nature. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_166

Environmental exposure to nitrosamines is associated with the development of cancer in a variety of target organs. One such carcinogen, N-methyl-N-nitrosurea (MNU), has long been used to induce mammary tumors in rats, which provide a useful model to study mammary carcinogenesis. However, some poorly clarified issues remain, such as the lack of a clear description of morphological patterns of tumors and the distribution and role of estrogen receptors (ERs) during tumor progression, as tumors overexpressing ERs show a paradoxical tendency to recur after ovariectomy. Mammary carcinomas were induced in Sprague-Dawley rats using MNU. The tumors were studied histologically and distribution of smooth muscle actin and ERs was studied immunohistochemically. All tumors presented both an epithelial and a myoepithelial component, demonstrated by immunohistochemical detection of smooth muscle actin. Tumors showed distinct histological patterns: well-differentiated papillary and adenoid areas and poorly differentiated solid and spindle-cell foci. Overexpression of ERs (>75% of labelled cells vs. 0-75% in control tissue) occurred in papillary and adenoid areas but not in solid and spindle-cell foci. Poorly differentiated tumor foci are likely to represent a more advanced, estrogen-independent phase in cancer progression and constitute the basis for tumor recurrence after ovariectomy.

Background Cutaneous mast cell tumours are one of the most common neoplasms in dogs and show a highly variable biologic behaviour. Several prognosis tools have been proposed for canine mast cell tumours, including histological grading and cell proliferation markers. CD117 is a receptor tyrosine kinase thought to play a key role in human and canine mast cell neoplasms. Normal (membrane-associated) and aberrant (cytoplasmic, focal or diffuse) CD117 immunoexpression patterns have been identified in canine mast cell tumours. Cytoplasmic CD117 expression has been found to correlate with higher histological grade and with a worsened post-surgical prognosis. This study addresses the role of CD117 in canine mast cell tumours by studying the correlations between CD117 immunoexpression patterns, two proliferation markers (Ki67 and AgNORs) histological grade, and several other pathological variables. Results Highly significant (p < 0,001) correlations were found between CD117 immunostaining patterns and histological grade, cell proliferation markers (Ki67, AgNORs) and tumoral necrosis. Highly significant (p < 0,001) correlations were also established between the two cellular proliferation markers and histological grade, tumour necrosis and epidermal ulceration. A significant correlation (p = 0.035) was observed between CD117 expression patterns and epidermal ulceration. No differences were observed between focal and diffuse cytoplasmic CD117 staining patterns concerning any of the variables studied. Conclusion These findings highlight the key role of CD117 in the biopathology of canine MCTs and confirm the relationship between aberrant CD117 expression and increased cell proliferation and higher histological grade. Further studies are needed to unravel the cellular mechanisms underlying focal and diffuse cytoplasmic CD117 staining patterns, and their respective biopathologic relevance.

Sebaceous gland carcinoma is a common tumour in male gerbils but, to date, no information is available on its immunohistochemical properties. This report describes the histopathological and immunohistochemical features of such a tumour from a 4.5-year-old male gerbil. The tumour immunoreactivity profile was studied in respect of p53 protein, CEA, EMA, c-erbB-2, cytokeratin (CK) 14 and the CKs detected by AE1/AE3 antibodies (i.e. high molecular weight CKs 1, 2, 3, 4, 5, 6, 10, 14, 15 and 16, and low molecular weight CKs 7, 8 and 19). The differences observed in p53 and c-erbB-2 immunolabelling between carcinomatous and hyperplastic areas suggest that p53 mutations and amplification of c-erbB-2 may play a significant role in the oncogenesis of sebaceous gland carcinoma in the gerbil.

In an immunohistochemical study of 25 canine chemodectomas, 17 tumours were stained with antisera to neurone specific enolase and the same number were stained for synaptophysin; a single tumour was stained for S100. Staining for Ki-67 occurred in 18 cases; the Ki-67-labelling index and the intensity of immunostaining was increased in more pleomorphic and malignant tumours, as assessed on histological grounds. Immunohistochemistry did not aid in recognition of less well-differentiated tumours.

BACKGROUND: While the deregulation of iron homeostasis in breast epithelial cells is acknowledged, iron-related alterations in stromal inflammatory cells from the tumor microenvironment have not been explored. METHODS: Immunohistochemistry for hepcidin, ferroportin 1 (FPN1), transferrin receptor 1 (TFR1) and ferritin (FT) was performed in primary breast tissues and axillary lymph nodes in order to dissect the iron-profiles of epithelial cells, lymphocytes and macrophages. Furthermore, breast carcinoma core biopsies frozen in optimum cutting temperature (OCT) compound were subjected to imaging flow cytometry to confirm FPN1 expression in the cell types previously evaluated and determine its cellular localization. RESULTS: We confirm previous results by showing that breast cancer epithelial cells present an 'iron-utilization phenotype' with an increased expression of hepcidin and TFR1, and decreased expression of FT. On the other hand, lymphocytes and macrophages infiltrating primary tumors and from metastized lymph nodes display an 'iron-donor' phenotype, with increased expression of FPN1 and FT, concomitant with an activation profile reflected by a higher expression of TFR1 and hepcidin. A higher percentage of breast carcinomas, compared to control mastectomy samples, present iron accumulation in stromal inflammatory cells, suggesting that these cells may constitute an effective tissue iron reservoir. Additionally, not only the deregulated expression of iron-related proteins in epithelial cells, but also on lymphocytes and macrophages, are associated with clinicopathological markers of breast cancer poor prognosis, such as negative hormone receptor status and tumor size. CONCLUSIONS: The present results reinforce the importance of analyzing the tumor microenvironment in breast cancer, extending the contribution of immune cells to local iron homeostasis in the tumor microenvironment context. info:eu-repo/semantics/publishedVersion