Study of genetic variants in chromosome 5p15.33 region in non-smoker lung cancer patients

Introduction: Genome-wide association studies have identified that genetic polymorphisms in the telomerase reverse transcrip-tase (TERT) and cleft lip and palate transmembrane 1-like (CLPTM1L) genes may play important roles in the development of lung cancer in never smokers.Material and methods: This study was aiming to evaluate the associations between the risk of lung cancer in never smokers and single nucleotide polymorphisms in these genes by Real-Time Taqman assay, in forty lung cancer patients and forty apparently healthy age-matched controls selected from the chest department, Kasr Al-Ainy hospital from June 2018 to January 2019. Results: Adenocarcinoma was the most common histopathological subtype of lung cancer in the study patients. Also, the prevalence of females having adenocarcinoma was more common than males. The heterozygous form of the CLPTM1L occurred more frequently in the subjects aged above 46 years (P=0.019). There was a significant association between (rs 2730100) (c. 1574-3777C>A) TERT and CLPTM1L (rs 451360) (c.1532+ 1051C>A) genotypes and the incidence of lung cancer in never smokers, especially adenocarcinoma, a subtype of non-small cell lung carcinoma (NSCLC).Conclusions: Polymorphism in the telomerase reverse transcriptase (TERT) and cleft lip and palate transmembrane 1 like (CLPT-M1L) genes may play an important role in the development of NSCLC, especially adenocarcinoma subtype. The two genes are located in the chromosome 5p15.33

Sinonasal Hyalinizing Adenoid Cystic Carcinoma Is Molecularly Different from Its Salivary and Breast Counterparts

Adenoid cystic carcinoma (AdCC) is known to behave differently based on its location, histologic features, and molecular profile. Despite this understanding, efforts to use these molecular findings to develop personalized treatments have not yet been successful. The purpose of this retrospective study is to examine the molecular characteristics of AdCC with various histologic features in three different locations. A reference group of 20 classic cribriform AdCC cases from the parotid gland was included, along with 10 salivary AdCCs (Group 1), 10 sinonasal AdCCs with hyalinization (Group 2), and 10 solid mammary AdCCs with basaloid features (Group 3). Tissue samples were processed and tested using various molecular techniques, and the Wilcoxon signed-rank test was used to compare the different groups. Molecular data were obtained for both common and rare cases of sinonasal, salivary, and mammary AdCCs, revealing differences in molecular features depending on the tumor’s location. The molecular profile of the AdCCs in the experimental group varied depending on the site, with MYB gene rearrangements being common in all cases. We report the first MYB::KMT2C/D fusions in a subset of salivary AdCCs and sinonasal AdCCs but not in mammary adenoid cystic carcinoma with basaloid features. We conclude that co-occurring genetic alterations may vary among different sites and may have implications for the prognosis and treatment plan of AdCC. More research is needed to fully understand the mechanisms of KMT2C and KMT2D mutations in the development and progression of head and neck cancer, including their interactions with the NOTCH pathway

Study of Genetic Variants in Chromosome 5p15.33 Region in Non-Smoker Lung Cancer Patients

Introduction: Genome-wide association studies have identified that genetic polymorphisms in the telomerase reverse transcrip-tase (TERT) and cleft lip and palate transmembrane 1-like (CLPTM1L) genes may play important roles in the development of lung cancer in never smokers. Material and methods: This study was aiming to evaluate the associations between the risk of lung cancer in never smokers and single nucleotide polymorphisms in these genes by Real-Time Taqman assay, in forty lung cancer patients and forty apparently healthy age-matched controls selected from the chest department, Kasr Al-Ainy hospital from June 2018 to January 2019. Results: Adenocarcinoma was the most common histopathological subtype of lung cancer in the study patients. Also, the prevalence of females having adenocarcinoma was more common than males. The heterozygous form of the CLPTM1L occurred more frequently in the subjects aged above 46 years (P = 0.019). There was a significant association between (rs 2730100) (c. 1574-3777C>A) TERT and CLPTM1L (rs 451360) (c.1532+ 1051C>A) genotypes and the incidence of lung cancer in never smokers, especially adenocarcinoma, a subtype of non-small cell lung carcinoma (NSCLC). Conclusions: Polymorphism in the telomerase reverse transcriptase (TERT) and cleft lip and palate transmembrane 1 like (CLPT-M1L) genes may play an important role in the development of NSCLC, especially adenocarcinoma subtype. The two genes are located in the chromosome 5p15.33

Hepatitis E Virus Mediates Renal Injury via the Interaction between the Immune Cells and Renal Epithelium

Renal disorders are associated with Hepatitis E virus (HEV) infection. Progression to end-stage renal disease and acute kidney injury are complications associated with HEV infection. The mechanisms by which HEV mediates the glomerular diseases remain unclear. CD10+/CD13+ primary proximal tubular (PT) epithelial cells, isolated from healthy donors, were infected with HEV. Inflammatory markers and kidney injury markers were assessed in the presence or absence of peripheral blood mononuclear cells (PBMCs) isolated from the same donors. HEV replicated efficiently in the PT cells as shown by the increase in HEV load over time and the expression of capsid Ag. In the absence of PBMCs, HEV was not nephrotoxic, with no direct effect on the transcription of chemokines (Cxcl-9, Cxcl-10, and Cxcl-11) nor the kidney injury markers (kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin 18 (lL-18)). While higher inflammatory responses, upregulation of chemokines and kidney injury markers expression, and signs of nephrotoxicity were recorded in HEV-infected PT cells cocultured with PBMCs. Interestingly, a significantly higher level of IFN-γ was released in the PBMCs-PT coculture compared to PT alone during HEV infection. In conclusion: The crosstalk between immune cells and renal epithelium and the signal axes IFN-γ/chemokines and IL-18 could be the immune-mediated mechanisms of HEV-induced renal disorder

Evidence of a Link between Hepatitis E Virus Exposure and Glomerulonephritis Development

Viruses can trigger glomerulonephritis (GN) development. Hepatitis viruses, especially Hepatitis C virus and Hepatitis B viruses, are examples of the viruses that trigger GN initiation or progression. However, the proof of a correlation between GN and Hepatitis E virus infection is not clear. Some studies confirmed the development of GN during acute or chronic HEV infections, mainly caused by genotype 3. While others reported that there is no relation between HEV exposure and GN development. A recent study showed that a reduced glomerular filtration rate was developed in 16% of acute HEV genotype 1 (HEV-1) infections that returned to normal during recovery. HEV-1 is endemic in Egypt with a high seroprevalence among villagers and pregnant women. There is no available data about a link between HEV and GN in Egypt. Methods: GN patients (n = 43) and matched healthy subjects (n = 36) enrolled in Assiut University hospitals were included in this study. Blood samples were screened for hepatotropic pathogens. Tests for HEV markers such as HEV RNA and anti-HEV antibodies (IgM and IgG) were performed. Laboratory parameters were compared in HEV-seropositive and HEV-seronegative GN patients. Results: Anti-HEV IgG was detected in 26 (60.5%) out of 43 GN patients. HEV seroprevalence was significantly higher in GN than in healthy controls, suggesting that HEV exposure is a risk factor for GN development. None of the GN patients nor the healthy subjects were positive for anti-HEV IgM or HEV RNA. There was no significant difference between seropositive and seronegative GN patients in terms of age, gender, albumin, kidney function profiles, or liver transaminases. However, anti-HEV IgG positive GN patients had higher bilirubin levels than anti-HEV IgG negative GN patients. HEV-seropositive GN patients had a significantly elevated AST level compared to HEV-seropositive healthy subjects. Conclusion: exposure to HEV infection could be complicated by the development of GN

Clinico-Pathological Features and Immunohistochemical Comparison of p16, p53, and Ki-67 Expression in Muscle-Invasive and Non-Muscle-Invasive Conventional Urothelial Bladder Carcinoma

Introduction: The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. Methods: Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. Results and conclusion: Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers’ expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas