Duchenne and Becker Muscular Dystrophy: Contribution of a Molecular and Immunohistochemical Analysis in Diagnosis in Morocco

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive disorders caused by mutations of the DMD gene located at Xp21. In DMD patients, dystrophin is virtually absent; whereas BMD patients have 10% to 40% of the normal amount. Deletions in the dystrophin gene represent 65% of mutations in DMD/BMD patients. To explain the contribution of immunohistochemical and genetic analysis in the diagnosis of these dystrophies, we present 10 cases of DMD/BMD with particular features. We have analyzed the patients with immunohistochemical staining and PCR multiplex to screen for exons deletions. Determination of the quantity and distribution of dystrophin by immunohistochemical staining can confirm the presence of dystrophinopathy and allows differentiation between DMD and BMD, but dystrophin staining is not always conclusive in BMD. Therefore, only identification involved mutation by genetic analysis can establish a correct diagnosis

Mélanome anorectal primitive

Nous proposons une étude rétrospective réalisée au sein du département de gastro-entérologie et d'Oncologie du CHU Casablanca colligeant tous les cas des mélanomes ano-rectaux primitifs, sur une période de 15 ans (du 1997 au 2012). Notre série comportait 14 patients, 8 hommes et 6 femmes avec une moyenne d'âge de 60,5 ans. Les signes cliniques étaient dominés par les rectorragies et le syndrome rectal (plus de 80% des malades). L'aspect tumoral noirâtre à été noté chez la moitié des malades. L'examen endoscopique a révélé une prédominance des lésions ulcérobourgeonnantes. Dans 5 cas la tumeur était plus haut située entre 5 à 8 cm de la marge anale. Le bilan d'extension avait décelé des métastases ganglionnaires, osseuses ou viscérales chez 7 malades. Un traitement chirurgical a été pratiqué chez 50% des malades (7 cas). Il a consisté en une exérèse locale isolée (2 cas) ou associée à une radiothérapie (2 cas) et une amputation abdomino-périnéale dans 3 cas. Quatre malades ont reçu une chimiothérapie et/ou radiothérapie palliative et dans deux cas on s'est contenté d'un traitement symptomatique. L'évolution a été marquée par une récidive chez les 2 patients traités par exérèse locale, dont un a été bénéficié d'une amputation abdomino-pelvienne de rattrapage et un des trois patients traités par chirurgie radicale. Deux patients sont en rémission complète après 36 mois de recul.Keywords: Mélanome anorectal, diagnostic, traitement, pronosti

High VISTA expression is linked to a potent epithelial-mesenchymal transition and is positively correlated with PD1 in breast cancer

Breast cancer is the most common type of tumor in women worldwide. Immune checkpoint inhibitors, particularly anti-PDL1, have shown promise as a therapeutic approach for managing this disease. However, this type of immunotherapy still fails to work for some patients, leading researchers to explore alternative immune checkpoint targets. The Ig suppressor of T cell activation domain V (VISTA) has emerged as a novel immune checkpoint that delivers inhibitory signals to T cells and has demonstrated encouraging results in various cancers. Our study investigated the association of VISTA expression with clinicopathological parameters in breast cancer patients, its involvement in the Epithelial-Mesenchymal-Transition (EMT) process, and its correlation with PD1 expression. Transcriptomic analysis revealed that VISTA was associated with lobular and metaplastic histological type, tumor size, lymph node status, ER and PR negative status, and the TNBC molecular subtype. Furthermore, VISTA expression was strongly associated with an immunosuppressive tumor microenvironment. Immunohistochemistry analysis corroborated the transcriptomic results, indicating that VISTA was expressed in most immune cells (94%) and was significantly expressed in breast cancer tumor cells compared to matched adjacent tissues. Our study also showed for the first time that VISTA overexpression in breast cancer cells could be associated with the EMT process. Additionally, we identified a positive correlation between VISTA and PD-1 expression. Together, these results highlight the immunosuppressive effect of VISTA in breast cancer patients and suggest that bi-specific targeting of VISTA and PD-1 in combination therapy could be beneficial for these patients

The immune checkpoint adenosine 2A receptor is associated with aggressive clinical outcomes and reflects an immunosuppressive tumor microenvironment in human breast cancer

BackgroundThe crosstalk between the immune system and cancer cells has aroused considerable interest over the past decades. To escape immune surveillance cancer cells evolve various strategies orchestrating tumor microenvironment. The discovery of the inhibitory immune checkpoints was a major breakthrough due to their crucial contribution to immune evasion. The A2AR receptor represents one of the most essential pathways within the TME. It is involved in several processes such as hypoxia, tumor progression, and chemoresistance. However, its clinical and immunological significance in human breast cancer remains elusive.MethodsThe mRNA expression and protein analysis were performed by RT-qPCR and immunohistochemistry. The log-rank (Mantel-Cox) test was used to estimate Kaplan-Meier analysis for overall survival. Using large-scale microarray data (METABRIC), digital cytometry was conducted to estimate cell abundance. Analysis was performed using RStudio software (7.8 + 2023.03.0) with EPIC, CIBERSORT, and ImmuneCellAI algorithms. Tumor purity, stromal and immune scores were calculated using the ESTIMATE computational method. Finally, analysis of gene set enrichment (GSEA) and the TISCH2 scRNA-seq database were carried out.ResultsGene and protein analysis showed that A2AR was overexpressed in breast tumors and was significantly associated with high grade, elevated Ki-67, aggressive molecular and histological subtypes, as well as poor survival. On tumor infiltrating immune cells, A2AR was found to correlate positively with PD-1 and negatively with CTLA-4. On the other hand, our findings disclosed more profuse infiltration of protumoral cells such as M0 and M2 macrophages, Tregs, endothelial and exhausted CD8+ T cells within A2ARhigh tumors. According to the Single-Cell database, A2AR is expressed in malignant, stromal and immune cells. Moreover, it is related to tumor purity, stromal and immune scores. Our results also revealed that CD8+T cells from A2ARhigh patients exhibited an exhausted functional profile. Finally, GSEA analysis highlighted the association of A2AR with biological mechanisms involved in tumor escape and progression.ConclusionThe present study is the first to elucidate the clinical and immunological relevance of A2AR in breast cancer patients. In light of these findings, A2AR could be deemed a promising therapeutic target to overcome immune evasion prevailing within the TME of breast cancer patients

Incidence of Gastric Cancer in Marrakech and Casablanca, Morocco

Gastric cancer is the fifth most common cancer globally with over 70% of new cases occurring in developing countries. In Morocco, oncologists in Marrakech suspected higher frequency of gastric cancer compared to Casablanca, a city 150 kilometers away. This study calculated age-specific, sex-specific, and total incidence rates of gastric cancer in Marrakech and was compared to the Casablanca population-based cancer registry. Using medical records from Center Hospital University Mohammad VI and reports from 4 main private pathology laboratories in Marrakech, we identified 774 patients for the period 2008–2012. Comparison of rates showed higher age-specific incidence in Marrakech in nearly all age groups for both genders. A higher total incidence in Marrakech than in Casablanca was found with rates of 5.50 and 3.23 per 100,000, respectively. Incidence was significantly higher among males in Marrakech than males in Casablanca (7.19 and 3.91 per 100,000, resp.) and females in Marrakech compared to females in Casablanca (3.87 and 2.58 per 100,000, resp.). Future studies should address possible underestimation of gastric cancer in Marrakech, estimate incidence in other regions of Morocco, and investigate possible risk factors to explain the difference in rates

The immune checkpoint VISTA is associated with prognosis in patients with malignant uveal melanoma

IntroductionUveal melanoma (UM) is a rare yet deadly tumor. It is known for its high metastatic potential, which makes it one of the most aggressive and lethal cancers. Recently, immune checkpoints such as Programmed cell Death protein-1 (PD1) and Cytotoxic T-Lymphocyte-Associated significantly increasing patient survival in multiple human cancers, especially cutaneous melanoma. However, patients with UMs were excluded from these studies because of their molecular characteristics, which tend to be widely different from those of cutaneous melanoma. This study aimed to analyze the expression of V domain Ig Suppressor T-cell Activation (VISTA), a novel immune checkpoint, to evaluate its prognosis significance and its correlation with PD1 and CTLA-4.MethodsEvaluation of VISTA, CTLA-4, and PD1 expression was performed through TCGA database analysis and immunohistochemistry using two independent cohorts with primary malignant UM.Results and discussionOur results showed that VISTA expression was associated with tumor aggressiveness, T cell exhaustion, and the shortest median overall survival among patients. Surprisingly, PD1 protein expression was negative in all patients, whereas CTLA-4 expression was high in patients with advanced stages. Our findings suggest that VISTA may be a prognostic marker and an attractive treatment strategy for immunotherapy in patients with UM. Exploring its expression profile may predict response to immunotherapy and may lead to the improvement of precision therapy in malignant uveal melanoma patients

Applying Geographic Information Systems (GIS) for surface condition indicators modeling of a flexible pavement

In Morocco, as in all world countries, deteriorating road conditions, increasing traffic loads, and decreasing funds have presented a complex management challenge for the road maintenance and rehabilitation process. Hence the need to assess the condition of the pavement network, decide on maintenance strategies, set rehabilitation priorities and implement a maintenance management system. In this regard, Geographic Information System (GIS) is a powerful tool for managing and analyzing data referenced to a geographic location, especially in the field of road infrastructure where information on pavement sections stored in textual databases can be linked by location and attribute in geographical maps. This paper presents a case study, explores the ability of a GIS to visualize the different levels of surface degradation of flexible pavement through the analysis of GIS surface indicator matrices and the reduction of road databases containing the results of the environmental inspection carried out in 2018 on a 50 km section of the Moroccan national road number 06 from KP 0+080 to KP 0+130, applying the Moroccan method carried out by the Moroccan National Center for Road Studies and Research. These thematic maps can justify a budgetary request for the investment of public funds and help in maintenance decisions

A rare presentation of an acanthomatous ameloblastoma of mandibular ramus: Case report

Ameloblastoma is the most common benign odontogenic epithelial tumor. It is slowly progressive and locally destructive in nature; the mandible is the most frequent site of ameloblastoma, accounting for approximately 80% of cases, 70% of which are located in the posterior part, particularly of the molars or the ascending ramus. A number of histopathological variants exist, including acanthomatous ameloblastoma form, which is a rather rare variant.Acanthomatous ameloblastoma is usually found in the elderly and is also most frequently found in the canine region of dogs in the literature.We report here a rare case of mandibular acanthomatous ameloblastoma in a young man, treated by surgical resection

The Clinicopathological Features and Prognostic Significance of HER2-Low in Early Breast Tumors Patients Prognostic Comparison of HER-Low and HER2-Negative Breast Cancer Stratified by Hormone Receptor Status

Introduction. There has been increased interest in HER2-low breast tumors recently, as these tumors may have distinct clinical and molecular characteristics compared to HER2-negative and HER2-positive tumors. A new nomenclature has been proposed for HER2 1+ and HER2 2+ tumors that are confirmed negative according to fluorescence in situ hybridization (FISH). These tumors are now referred to as HER2-low, and it is thought that they may represent a distinct subtype of breast cancer that warrants further investigation. In this study, we aimed to evaluate the clinicopathological characteristics and prognostic impact of this particular subtype in a North-African context where HER2-low breast cancer is a relatively understudied subtype, particularly in non-Western populations. Methods. We conducted a retrospective cohort study on 1955 breast tumors in Moroccan patients over 10 years, collected at the Pathology Department of Ibn Rochd University Hospital in Casablanca and at the pathology department of Hassan II University Hospital in Fes. We elaborated on their complete immunohistochemical profile based on the main breast cancer biomarkers: Ki-67, HER2, estrogen, and progesterone receptors. Their overall survival and disease free survival data were also retrieved from their respective records. Results. Out of 1955 BC patients, 49.3% were classified as HER2-low; of which 80.7% and 19.2% were hormone receptors positive and negative, respectively. The clinicopathologic features indicate that HER2-low subtype tumors behave much more like HER2-positive than HER2-negative tumors. The survival analysis showed that the HER2-low subtype-belonging patients present significantly the poorest prognosis in disease-free survival (p=0.003) in comparison with HER2-negative ones. When considering the hormonal status, hormonal-dependent tumors show a significant difference according to HER2 subtypes in disease-free survival (p<0.001). Yet no significant difference was shown among hormonal negative tumors. Moreover, patients with hormonal positive tumors and simultaneously belonging to the HER2-low subgroup present a significantly good prognosis in overall survival compared to the ones with hormonal negative tumors (p=0.008). Conclusion. Our study has shown that the HER2-low phenotype is common among hormone-positive patients. The clinicopathological features and prognostic data indicate that the hormonal receptors effect and HER2 heterogeneity are crucial factors to consider. It is important to note that this particular subgroup is different from the HER2-negative one and should not be treated in the same way. Therefore, this study offers a new perspective in the management of HER2-low patients and can serve as a basis for future prospective analyses