MDM2 (T309G) Gene Polymorphism Determines the Susceptibility of Hepatocellular Carcinoma in Bangladesh

Background: Hepatocellular carcinoma (HCC) is one of the fatal cancer types worldwide, and a variety of genetic factors are considered to be associated with this incidence. MDM2 gene plays a pivotal role in various pathways, which are essential to combat tumor formation. The study aimed to find out the associations of MDM2 (T309G, rs2279744) gene polymorphism with the development of HCC in the Bangladeshi population. Methods: A case-control study on 100 HCC patients and 110 control subjects was conducted. The genotyping of the MDM2 (T309G) gene was done using PCR-RFLP methods. Results: The percentage of TT and GG genotypes were significantly different (p<0.01) among the study subjects. There were four genotyping groups, while the subjects with TT genotypes were considered the reference group. Patients with GG genotypes were at high risk of developing HCC (OR, 3.6; 95 % CI, 1.64–7.80; p<0.01) compared to the control. On the other hand, the association of TG genotypes with HCC was not statistically significant (OR, 1.8; 95 % CI, 0.91–3.40, p>0.05). In addition, patients having either GG or TG genotypes showed higher risk for HCC compared to control group (OR = 2.20; 95% CI = 1.21–4.14; P < 0.05). Conclusion: Our study suggested that the MDM2 gene may have a strong association with the development of HCC, and the GG allele could serve as an essential determinant to identify the higher risk of HCC in the Bangladeshi population.

Hematologic Presentations of COVID-19 Can be Misinterpreted as Acute Myeloid Leukemia

Introduction: COVID-19 infection prompts inflammatory responses and acute lung injury in human beings. Complete blood count with differential is essential investigative tool in its managing. However, very few studies revealed the variations of blood cell morphology in this disease.Case report: We reported a 39-years- old female patient complained of respiratory distress one week prior to hospitalization. The patient suffered from cough, fever, and molecular test was reported positive for COVID-19 infection. Laboratory data revealed severe permanent leukopenia and peripheral blood smear examination showed blastoid cells after remission of respiratory signs. Patient underwent bone marrow biopsy for rule out acute myeloid leukemia. But, on bone marrow sample, only viral cytopathic effects were seen. COVID-19 virus stimulates inflammatory cells to produces various inflammatory cytokines and as a result, viral cytopathic effects on white blood cells is seen. Conclusion: We have described how the characteristic peripheral blood findings of COVID‐19 infection can be misinterpret as acute myeloid leukemia.

Betel Quid, Smoking and Alcohol Dependency among Patients with Oral Potentially Malignant Disorders and Oral Cancer in Sri Lanka; A Preliminary Case-control Study

Introduction: Oral cancer and Oral Potentially Malignant Disorders (OPMDs) arising due to risk habits like betel quid (BQ) chewing, smoking and alcohol use are preventable despite the high prevalence and poor survival rates. However, dependence to risk habits has become a barrier to prevent OPMDs and oral cancer. Objectives: This study was conducted to determine the dependence to risk habits among patients with such oral lesions, and the quitting among dependent users after diagnosis. Materials and method: A case-control study was conducted among 100 participants, 50 diagnosed with OPMDs and oral cancer from two Oral and Maxillo Facial clinics in Sri Lanka and a similar control group without any oral lesions. All participants practiced one or more risk habits such as BQ chewing, smoking and/or alcohol use. Dependence was assessed using Sinhala language translations of standardized scales such as Betel Quid Dependence Scale for BQ chewers, Fagerstrom Test for Nicotine Dependence for tobacco smokers and CAGE (“Cut down”, “Annoyed”, “Guilty” and “Eye opener”) scale for alcohol users. Results: Dependence on habits was more among the case group (BQ-93%; smoking-14%; alcohol-66%). Quitting rates of BQ and alcohol among those who were diagnosed with oral cancer [BQ (89%), alcohol (89%)] were higher (p<0.05) than those with OPMDs [BQ (50%), alcohol (22%)]. Lack of awareness due to low socio-economic status (97%) was a significant association for BQ dependence (p=0.01).Conclusion: In conclusion, development of OPMDs and oral cancer increases with dependence to BQ chewing, smoking and alcohol use. Increased awareness about OPMDs and its risk of malignancy is needed among public. Prevention of dependence to these risk habits also becomes essential.

Significance of Immunohistochemical Expression of Survivin in Renal Cell Carcinoma

Background: Evasion of apoptosis is an essential alteration for cellular genetic mutation. Survivin is a member of inhibitor of apoptosis protein (IAP) family. Under normal conditions, Survivin is expressed in embryonic and fetal tissues and markedly diminished in mature, differentiated adult tissues. Survivin was found to be re-expressed in multiple solid and hematological human malignant neoplasms. The purpose of this study was to evaluate the expression of Survivin in renal cell carcinoma (RCC), and to find statistically significant associations between Survivin and the tested Clinicopathological parameters.Methods: 39 patients with RCCs who underwent nephrectomy were included in the study. From each RCC specimen, two tissue sections were obtained; one was stained by H&E stain to determine both RCC phenotype and Fuhrman’s nuclear grades. The second tissue section was immunohistochemically stained by anti-human Survivin antibody. Results: The study revealed statistically significant associations between Survivin expression in RCC specimens and RCC histological types (p =0.002), high tumor grade (p< 0.001) and advanced tumor stage (p< 0.001). Conclusion: The study revealed that Survivin is positively correlated to poorly differentiated RCCs with high Fuhrman’s nuclear grade and advanced tumor stage.

Histopathologic Characteristics of Invasive and Non-invasive Ductal Tumors have Relationship with Different Phenotypes of ER / PR Receptors in Breast Cancer Patients

Objective: Contradictory reports have been published regarding the expression levels of the hormone receptors of estrogen and progesterone (ER / PR) and theirclinical importance in diagnosis of breast cancer. The aim of this study was to evaluate the relationship between pathological features of invasive and non-invasive ductal tumors by different ER / PR phenotypes. Methods: This descriptive-analytical study was performed on 74 specimens of breast cancer referred to Isfahan Hospitals for diagnosis between 2015 - 2018. After fixation of the specimens in formalin, tissue passage, cross section and H / E staining, the specimens were divided into two groups: non- invasive and Invasive ductal Carcinoma. After removing of mask, expression of different ER / PR phenotypes was performed using primary monoclonal antibody and immunohistochemically methods. Results: From 74 malignant specimens, 61 (82.4%) were in the category of invasive ductal tumors and 13 cases (17.6%) were in the category of non-invasive ductal tumors. Out of 73 patients with positive ER or PR phenotype 47 samples (63.5%) had ER + / PR +phenotypes, 6 samples had (8.1%) ER+ / PR –phenotype, 20 samples (27%) had ER- / PR + phenotype and only one sample (1.4%) had the ER- / PR- phenotype and was in the category of invasive ductal tumors. There was not detected ER- / PR- phenotype expression in non-invasive ductal tumor. Further analysis showed that there were not significant difference between ER / PR phenotype and tumor stage (p =0.36) or with tumor Grade (P=0.38), high age of menopause or post menopause (P> 0.05). Conclusion: Our data shows that expression of ER- / PR- phenotype only was detected in invasive ductal tumor. It is thought that the tumor type maybe affects the expression of different types of ER / PR hormone receptor phenotypes in breast cancer patients.

Comprehensive Analysis of the Expression and Prognosis for DCTPP1 gene in Breast Cancer

Background: Breast cancer is a common malignancy in women. DCTPP1 is a potential target for the development of antitumor drugs, and plays an important role in the process of DNA replication. Aims: To investigate the biological role of DCTPP1 gene, as well as its expression in breast cancer and its relation to patient prognosis. Materials and Methods: Breast cancer data was derived from the TCGA database. Using the UALCAN database, the expression level of DCTPP1 mRNA in breast cancer tissues was investigated. The expression of DCTPP1 in various pathological types of breast cancer was studied using the Human Protein Atlas. UALCAN was also used to investigate the relationship between DCTPP1 gene expression and breast cancer patient prognosis. Bioinformatics studied the proteins related to DCTPP1 expression and their roles in the GeneMANIA and WebGestalt databases. Results: DCTPP1 mRNA was significantly expressed in breast cancer compared to normal breast tissue (P<0.001). DCTPP1 was shown to be highly expressed in breast cancer tissues from different pathological types and stages (P<0.001). The DCTPP1 protein was expressed at a higher frequency in breast cancer than in normal breast tissue. When compared to patients with low DCTPP1 expression, patients with high DCTPP1 expression had a considerably shorter overall survival time. The 20 proteins related to DCTPP1 expression were mostly located in the nucleus and membrane, and were involved in biological regulation, stimulus response, metabolic process, and other processes, according to gene ontology analysis. It plays an important role in protein binding, ion binding, and nucleic acid binding. Conclusion: DCTPP1 is highly expressed in breast cancer, and is associated to a poor prognosis for patients with breast cancer. DCTPP1 may be a potential therapy and intervention target for breast cancer.

Association of NQO1 C609T (Pro187Ser) with Risk of Oral Submucous Fibrosis in Eastern Indian Population

Objective: Oral submucous fibrosis (OSF) is a debilitating disease mainly attributed to chewing areca nut with a 7.4-13% malignant transformation rate. The present study explores the role of NADPH quinone oxidoreductase 1 (NQO1) C609T (Pro187Ser) polymorphism in susceptibility to OSF among habitual areca nut chewers in an eastern Indian population. Material and Methods: In this hospital-based study, 152 controls and 179 OSF cases were genotyped at NQO1 C609T polymorphic site by PCR-RFLP and its effect on NQO1 expression in OSF tissue was studied to determine the risk of the disease. Results: Overall, about 18% of the total OSF cases were detected carrying minor TT alleles (Ser/Ser) p=0.026. When categorized by age, both CT (Pro/Ser) and TT (Ser/Ser) alleles were significantly higher (p= 0.003 & 0.004 respectively) in cases above 40years of age. NQO1 protein was 42% reduced in buccal tissues of heterozygous (Pro/Ser) carriers, whereas a 70% reduction was observed in TT (Ser/Ser) OSF cases. Conclusion: Our study suggests that the NQO1 C609T polymorphism confers increased risk for OSF in habitual chewers.

Poor Man’s Cell-block Preparation, a Novel Idea which Can be Applied to Basic Health Care Facilities in Resource-poor Settings

Objective: To determine the diagnostic yield of cell blocks, prepared by the vapour fixation method, using laboratory supplies easily available at any low resource laboratory setup or outpatient department of a basic healthcare unit. Methods: Prospective descriptive study was carried out at Healthways Laboratories Rawalpindi, for 6 months from 1st January 2017 to 30th June 2017. Walk in patients referred to the lab for FNAC were selected by non probability convenient sampling. After preparing FNAC slides from first pass, the patients were briefed about the cell block material and after informed consent second dedicated passes were done to make cell blocks. Results: Out of 47 cases, there were 25 (53.2 %) breast lumps, 8 (17%) superficial collections, 7 (15.1%) lymphadenopathies, 6 (12.8%) thyroid swellings and 1 salivary gland swelling. Technique yielded moderate to high cellularity in 33 (70.2%) cases, 16 from malignant and 1 from benign breast lumps, 5 from thyroid, 3 from reactive and 3 from metastatic lymphnodes, 3 from abscesses, 1 from lipoma and 1 from salivary gland. Low cellularity 14 (29.8%) cases were from 5 benign and 3 malignant breast lumps, 2 hematomas and 1 case each from thyroid, metastatic lymphnode, abscess and lipoma. Good cellularity was achieved in 16 (84.2%) of 19 cases of malignant breast lesions, 3 (15.8%) were hypo cellular of which 1 was non-diagnostic on FNAC smear. Cell block diagnosis was comparable to FNAC in 35 of 47 (74.4%) cases. Non diagnostic cases on cell block were more, 13 versus 3 cases on FNAC. The kappa value of agreement in diagnosis was 0.64. Conclusions: Poor man’s cell block method is simplest and effective method of cell block preparation which must be advocated at basic healthcare units and low tech laboratory. Its diagnostic potential must be further explored.

Molecular Genetics of Esophageal Cancer : Indian Perspective

Background: RIZ1 is one of the tumor-suppressor genes that is silenced in many human cancers. Change in RIZ1 expression has not been reported in ESCC patients. Therefore, the aim of this study was to investigate the role of RIZ1 in ESCC in the Indian population. Methods: Twelve esophageal squamous-cell carcinoma (ESCC) patients in stage IV and 12 healthy individuals were used in this study. Tissue sampling was taken from individuals and total RNA was isolated and then cDNA was synthesized using PCR. RIZ1 primers were then designed, and RIZ1 expression was quantified by qRT-PCR. Mapping of CpG islands in RIZ1 promoter was performed using bioinformatics tools. The promoter methylation status of this gene was studied using u methylation-specific PCR (MSP). T-student test was used to analyze the data.Results: Decreased RIZ1 expression was observed in ESCC compared with healthy controls. The results showed a relatively higher density of CpG dinucleotides in the RIZ1 promoter. No significant difference in promoter methylation was observed in blood and tissue samples.Conclusion: The study showed a significant down-regulation of RIZ-1 gene in the blood and tissue samples of ESCC patients that did not related to the altered promoter methylation.

Prevalence of BRAF V600E Mutation in the Iranian Patients with Hairy Cell Leukemia: A Retrospective Study

Objective: BRAF V600E mutation has several implications in hairy cell leukemia (HCL). The prevalence of This mutation has been investigated in various populations, but not in Iran. In this study, we evaluated the prevalence of BRAF V600E mutation in an Iranian HCL population as well as its association with the patients’ characteristics.Methods: In a retrospective (archival) study, 20 HCL patients with the confirmed immunophenotypic and morphologic diagnosis were included. Paraffin-embedded blocks of bone marrow aspirate were used to investigated BRAF V600E mutation using amplification refractory mutation system (ARMS) PCR. Demographic, clinical, laboratory, and immunophenotypic characteristics of patients were extracted from the patients medical profiles.Result: BRAF V600E mutation was present in 17 (85%) HCL patients and absent in three (15%) patients. The mean age of the patients was 44.76 ± 8.69 years in mutation-positive and 62.33 ± 8.69 in mutation-negative patients. This difference was statistically significant (p=0.013). No significant difference was found between the laboratory indices of the mutation-positive and mutation-negative groups. The clinical, morphologic, and immunophenotypic characteristics of the two groups were also statistically comparable.Conclusion: BRAF V600E mutation is present in the majority of the Iranian HCL patients and is associated with younger age of presentation.