New Insights Into the Role of Tissue Eosinophils in the Progression of Colorectal Cancer: A Literature Review

Introduction: Amongst the inflammatory cells implicated in the immune surveillance of colorectal cancer, a growing body of evidence suggests a role for eosinophils in carcinogenesis. We aimed to review the value of tumour-associated tissue eosinophilia (TATE) in the prognosis of colorectal cancer emphasizing the identification and measurement of tissue-infiltrating eosinophils and their association with the clinicopathological features of the disease. Material and Methods: We used PubMed and Web of Science search engines to retrieve studies that looked at the association between tissue eosinophils and colorectal cancer prognosis. Results: We selected 15 studies for our review. In the majority of the studies, eosinophils were identified in hematoxylin-eosin stained sections and scores were generated for analysis. Most of the studies pointed to tumour-associated tissue eosinophilia as a favourable prognostic marker in colorectal cancer and found an inverse association between eosinophil count and the metastatic potential of these neoplasms. The association between tumour-associated tissue eosinophilia and established prognostic markers of colorectal cancer was assessed in some studies, with inconsistent results. Additionally, tumour-associated tissue eosinophilia decreased with the adenoma-carcinoma progression of colorectal lesions. Discussion: Several mechanisms have been proposed regarding eosinophil chemoatraction to tumour tissues and eosinophil-cancer cell cross-talk, suggesting that eosinophils are actively involved in colorectal cancer progression. Although a scoring system is still lacking, tumour-associated tissue eosinophilia meets the criteria of a convenient histopathological prognosticator in colorectal cancer. Conclusion: Collectively, current evidence associates the presence of eosinophils in the colorectal cancer microenvironment with the modulation of tumour progression. The clinical impact of this finding deserves future research

Presence and significance of Helicobacter spp. in the gastric mucosa of Portuguese dogs

Background: Non-Helicobacter pylori Helicobacters (NHPH) are also able to cause disease in humans. Dogs are a natural reservoir for many of these species. Close and intense human contact with animals has been identified as a risk factor and therefore, an important zoonotic significance has been attributed to NHPH. Methods: To determine the prevalence of Helicobacter species and the gastric histopathological changes associated, gastric mucosa samples of 69 dogs were evaluated. Results: Only one dog presented a normal histopathological mucosa with absence of spiral-shaped organisms. A normal gastric mucosa and the presence of spiral-shaped bacteria was observed in two dogs. All remaining animals presented histopathological changes representative of gastritis. Helicobacter species were detected in 60 dogs (87.0%) by at least one detection method. Histological, histochemical and immunohistochemical evaluations revealed that Helicobacter spp. were present in 45 (65.2%), 52 (75.4%) and 57 (82.6%) dogs, respectively. Spiral-shaped bacteria were detected by qPCR analysis in 33 (47.8%) dogs. H. heilmannii-like organisms were identified in 22 animals (66.7%) and predominantly in the antral gastric region. H. salomonis was the second most prevalent species (51.5%) although it was mainly found in association with other Helicobacter spp. and in the body gastric region. H. bizzozeronii and H. felis were less frequently detected. Conclusions: It was concluded that, despite the high incidence and worldwide distribution of gastric NHPH in dogs, the presence of specific Helicobacter species may vary between geographic regions. NHPH infections were significantly accompanied by mild to moderate intraepithelial lymphocyte infiltration and mild to moderate gastric epithelial injury, but a clear relationship between gastritis and Helicobacter infection could not be established

Contribuição para o estudo da biopatologia dos adenocarcinomas cutâneos em canídeos

Mestrado em Medicina e Oncologia MolecularMaster Degree Course in Molecular and Oncology MedicineCONTRIBUIÇÃO PARA O ESTUDO DA BIOPATOLOGIA DOS ADENOCARCINOMAS CUTÂNEOS EM CANÍDEOS Ana Laura da Silva Santos Saraiva Mestrado em Medicina e Oncologia Molecular RESUMO Os adenocarcinomas cutâneos são tumores relativamente raros em canídeos, estando porém inseridos num grande grupo de neoplasias, com uma expressão bastante significativa na patologia veterinária os tumores epiteliais com diferenciação anexal. Alguns autores fundamentam a reduzida incidência dos adenocarcinomas cutâneos no seu sub-diagnóstico. Assim sendo, uma caracterização mais precisa poderá ajudar no diagnóstico mais exacto e melhor fundamentado destas lesões. Tendo em vista este objectivo, foram analisados 31 tumores malignos com diferenciação glandular, em canídeos: 8 tumores malignos das glândulas apócrinas, 6 tumores malignos das glândulas ceruminosas, 7 carcinomas sebáceos e 10 carcinomas das glândulas perianais hepatóides. Na série em estudo, e sempre que possível, foram analisados alguns parâmetros clínicos tais como o sexo, a idade e a raça dos animais, assim como o tamanho, a localização e a evolução das lesões. Foram utilizados métodos histoquímicos e imuno-histoquímicos (citoqueratinas AE1/AE3 e 14, vimentina, p63, Ki-67) para a caracterização dos tumores. Através da análise dos resultados obtidos, verificámos que nenhuma raça demonstrou propensão para qualquer um dos tipos de tumores estudados. Os animais afectados tinham geralmente uma idade avançada, com médias entre os 8 e os 12 anos. Notou-se igualmente uma tendência sexual para os machos. A evolução das lesões foi por norma favorável, já que em nenhum caso se verificou metastização à distância, mesmo quando se observou invasão vascular, e raras foram as recidivas locais das lesões. A análise histopatológica dos adenocarcinomas cutâneos permitiu uma caracterização mais cuidada dos vários grupos de tumores, tendo-se verificado uma tendência para a invasão da epiderme, ulceração, necrose e infiltração inflamatória mononuclear. O estudo imuno-histoquímico permitiu reconhecer a CK14, a p63 e a calponina como marcadores moleculares úteis no diagnóstico e caracterização destes tumores. O índice de proliferação dos carcinomas cutâneos com diferenciação glandular foi determinado pelo uso do anticorpo anti-Ki-67, tendo-se revelado uma técnica sensível e com perspectivas de poder ser utilizada no estabelecimento do comportamento biológico dos adenocarcinomas cutâneos.CONTRIBUTION FOR THE STUDY OF THE BIOPATHOLOGY OF CANINE CUTANEOUS ADENOCARCINOMAS Ana Laura da Silva Santos Saraiva Mestrado em Medicina e Oncologia Molecular ABSTRACT The cutaneous adenocarcinomas are included in the wide group of the epithelial tumours with adnexal differentiation which, although relatively rare in dogs, are of importance in veterinary pathology. Some authors suggest that the small incidence of the cutaneous adenocarcinomas is due to their non- or misdiagnosis. Therefore, a more precise characterization of these tumours will be of help for a better diagnostic of these lesions. We analysed 31 malignant tumours with glandular differentiation, in dogs: 8 apocrine malignant tumours, 6 ceruminous malignant tumours, 7 sebaceous carcinomas and 10 hepatoid gland carcinomas. In our study sample, and whenever possible, we analysed several clinical parameters, namely the sex, age and breed of the animals, and size, position and evolution of the lesions. We also used histochemistry and immuno-histochemestry (cytokeratins AE1/AE3 and 14, vimentin, p63, calponin and Ki-67) to further characterize the tumours under study. Our results showed that the incidence of the studied tumours did not relate to the breed, was higher in older animals (8-12 years) and affected males more than females. The clinical evolution of the lesions was normally favourable as no distant metastases were observed, even when vascular invasion was present. Also, local recurrence was rare. Our histopathological analysis revealed that these tumours had a tendency for epidermis invasion, ulceration, necrosis and mononuclear inflammatory infiltration. By immuno-histochemistry we showed that CK14, p63 and calponin can be used as molecular markers for the diagnosis and characterization of the cutaneous adenocarcinomas. We determined the proliferation index of the various tumours using a specific antibody anti-Ki-67 and showed that this is indeed an accurate technique that can be used in future to further characterize the biological behaviour of the cutaneous glandular carcinomas

Proliferative Endometrial Lesions Hidden behind the Feline Pyometra

The literature refers to pyometra as the most important pathology in the feline uterus, which is often associated with cystic endometrial disease (cystic endometrial hyperplasia/pyometra complex or CEH-Pyo). The etiology of pyometra is complex and probably multifactorial, but hormonal influences are suggested to play an important role in the pathogenesis. Progestagen-based contraceptives may be risk factors for the CEH-Pyo syndrome, for endometrial adenocarcinoma and also to mammary tumors in this species

Novel and Recurrent PNPLA1 Mutations in Spanish Patients with Autosomal Recessive Congenital Ichthyosis; Evidence of a Founder Effect

Autosomal recessive congenital ichthyosis (ARCI) is a group of rare non-syndrome diseases that affect cornification. PNPLA1 is one of the 12 related genes identified so far. Mutation screening of this gene has resulted in the identification of 13 individuals, from 10 families, who carried 7 different PNPLA1 mutations. These mutations included 2 missense, 2 frame­shift and 3 nonsense, 3 of them being novel. One of the identified variants, c.417_418delinsTC, was highly prevalent, as it was found in 6 out of 10 (60%) of our ARCI families with PNPLA1 mutations. Clinical manifestations varied significantly among patients, but altered sweating; erythema, palmar hyperlinearity and small whitish scales in flexor-extensor and facial areas were common symptoms. Haplotype analyses of c.417_418delinsTC carriers confirmed the existence of a common ancestor. This study expands the spectrum of the PNPLA1 disease, which causes variants and demonstrates that the c.417_418delinsTC mutation has founder effects in the Spanish population.This work was partially supported by Ramón Areces Foundation project (Rare Diseases 2013-056); by Spanish Instituto de Salud Carlos III (ISCIII) (INT15/00070, INT16/00154, INT17/00133) and by Xunta de Galicia (IN607B). UE was supported by a predoctoral fellowship from Xunta de GaliciaS

Mycobacterium tuberculosis strains are differentially recognized by TLRs with an impact on the immune response

Tuberculosis associates with a wide spectrum of disease outcomes. The Beijing (Bj) lineage of Mycobacterium tuberculosis (Mtb) is suggested to be more virulent than other Mtb lineages and prone to elicit non-protective immune responses. However, highly heterogeneous immune responses were reported upon infection of innate immune cells with Bj strains or stimulation with their glycolipids. Using both in vitro and in vivo mouse models of infection, we here report that the molecular mechanism for this heterogeneity may be related to distinct TLR activations. Among this Mtb lineage, we found strains that preferentially activate TLR2, and others that also activate TLR4. Recognition of Mtb strains by TLR4 resulted in a distinct cytokine profile in vitro and in vivo, with specific production of type I IFN. We also uncover a novel protective role for TLR4 activation in vivo. Thus, our findings contribute to the knowledge of the molecular basis underlying how host innate immune cells handle different Mtb strains, in particular the intricate host-pathogen interaction with strains of the Mtb Bj lineage.This work has been funded by Fundacao para a Ciencia e Tecnologia, Portugal. Project grants: PTDC/SAU-MII/101977/2008 and PTDC/BIA-BCM/102776/2008. Personal grants: SFRH/BD/35981/2007 to JC; SFRH/BPD/3306/2007 to AC; SFRH/BPD/77399/2011 to LMT; SFRH/BI/33456/2008 to CS; and SFRH/BPD/33959/2009 to NSO. MS is a Ciencia 2007 fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A novel ABCA12 pathologic variant identified in an Ecuadorian harlequin ichthyosis patient: A step forward in genotype‐phenotype correlations

Autosomal recessive congenital ichthyoses (ARCI) have been associated with different phenotypes including: harlequin ichthyosis (HI), congenital ichthyosiform erythroderma (CIE), and lamellar ichthyosis (LI). While pathogenic variants in all ARCI genes are associated with LI and CIE phenotypes, the unique gene associated with HI is ABCA12. In HI, the most severe ARCI form, pathogenic variants in both ABCA12 gene alleles usually have a severe impact on protein function. The presence of at least one non-truncating variant frequently causes a less severe congenital ichthyosis phenotype (LI and CIE). METHODS: We report the case of a 4-year-old Ecuadorian boy with a severe skin disease. Genetic diagnosis was performed by NGS. In silico predictions were performed using Alamut software v2.11. A review of the literature was carried out to identify all patients carrying ABCA12 splice-site and missense variants, and to explore their genotype-phenotype correlations. RESULTS: Genetic testing revealed a nonsense substitution, p.(Arg2204*), and a new missense variant, p.(Val1927Leu), in the ABCA12 gene. After performing in silico analysis and a comprehensive review of the literature, we conclude that p.(Val1927Leu) affects a well conserved residue which could either disturb the protein function or alter the splicing process, both alternatives could explain the severe phenotype of our patient. CONCLUSION: This case expands the spectrum of ABCA12 reported disease-causing variants which is important to unravel genotype-phenotype correlations and highlights the importance of missense variants in the development of HI. © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.Fundación Ramón ArecesInstituto de Salud Carlos IIIXunta de GaliciaUniversidad Espíritu Santo-Ecuado