Malaysian Journal of Pathology最新文献

Introduction: Extracellular vesicles (exosome-like vesicles) are small membrane vesicles ranging from 20-200nm in size that are released by various cells into the extracellular space. These extracellular vesicles play a major role in cell-to-cell communication and contain materials, such as proteins, mRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). The effect of exosomes derived from an invasive colon cancer cell line on angiogenesis is unclear. Hence, the aim of this study is to investigate the effect of exosomes derived from an invasive colon cancer cell line on angiogenesis of endothelial cells.

Materials and methods: In the present study, the exosomes from the cell culture supernatants of an invasive colon cancer cell line SW480-7 were characterised. The effect on tube formation and expression of angiogenic genes in a microvascular endothelial cell, telomerase-immortalised microvascular endothelial cell (TIME) was examined after co-cultured with exosomes secreted from SW480-7.

Results: Zetasizer result showed average diameter of exosomes derived from SW480-7 was 246.2 nm and morphological analysis showed the size of majority of exosomes were less than 200 nm. Results showed that exosomes derived from SW480-7 increased tube formation and up-regulated FGFR3 mRNA expression in TIME.

Conclusion: Our findings suggest that exosomes derived from SW480-7 increased tube formation and up-regulated expression of FGFR3 mRNA in TIME.

Breast carcinoma is the most common malignancy among women worldwide. Liquid biopsy is a method of obtaining tumour-derived material from blood and body fluid. This includes the assessment of circulating tumour cells (CTCs), circulating tumour deoxyribose nucleic acid (ctDNA), tumour educated platelets (TEPs) and exosomes. Detection of CTCs and ctDNA in liquid biopsy has been shown to have prognostic and predictive value in both early and metastatic breast carcinoma. The study of CTCs could also advance our understanding of aspects of tumour biology, including epithelial mesenchymal transition. ctDNA can be used to assess and monitor the molecular profile of breast carcinoma. It may help detect new genetic alterations in tumours and predict disease progression before the onset of clinical features or radiological evidence. TEPs and exosomes are also emerging as diagnostic, prognostic and predictive markers of breast carcinoma. Thus, liquid biopsy provides a non-invasive, repeatable method for the dynamic assessment of the tumour. Many methods have been used for the detection of CTCs and ctDNA. Most of these are still in the research stage and only the CellSearch method for the detection of CTCs and Therascreen PIK3CA RGQ polymerase chain reaction (PCR) assay for the detection of PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha) mutations in liquid biopsy have approval of the United States, Food and Drug Administration. However, their high costs, lack of standardized procedures, and a long and complicated detection process have limited their use. Despite its limitations, liquid biopsy is a useful tool in clinical decision making and has the potential to play an increasingly important role in the management of breast carcinoma in the future as we move toward more personalized cancer care.

Introduction: Mutations in FLT3 are the most commonly reported genetic changes in AML patients. These mutations are normally identified in approximately one third of newly diagnosed patients and are reported to have prognostic significance.

Materials and methods: Peripheral blood samples was collected from 63 AML patients to study their morphological, cytogenetic and molecular features. PCR was used to determine the prevalence of FLT3 mutations; internal tandem duplication (ITD) and tyrosine kinase domain (TKD) in AML patients.

Results: Among 63 AML patients, 42 were males and 21 were females with male to female ratio 2:1 with median age of 32 years. AML-M2 was the predominant French-American-British (FAB) subtype (42%) followed by M4 (27%), M3 (8%), M1 (8%), M0 (8%) and M5 (7%) respectively. Cytogenetic analysis of 60 patients showed 58% as cytogenetically normal (CN) whereas 42% had aberrant karyotype.The most frequent aberrations were trisomy8, t(8;21), t(15;17) (8.3%) each, inversion16 (5%), and different deletions (12%) respectively. FAB-M4 subtype showed most of the chromosomal anomalies. Among 63 AML patients, 22% showed FLT3/ITD while 6.4% had D835 mutation after molecular analysis. FLT3 mutations were found in most of the FAB subtypes and cytogenetic groups. FLT3/ITD mutations were more common in patients with normal karyotype (26%) and usually present with hyperleukocytosis but association between two was not significant.

Conclusion: The cytogenetic data of adult AML from Pakistan showed presence of favourable prognostic karyotype with comparable prevalence as reported in international data. Moreover, FLT3/ITD mutations are commonly found in our patients as determined by molecular analysis. Therefore, inclusion of this unfavourable prognostic marker should be routine in molecular diagnostic testing of AML.

No abstract available.

Prostate cancer is the second-most frequently diagnosed cancer in men worldwide. Serum prostatespecific antigen is currently used for the early detection of prostate cancer. However, new biomarkers are needed to decrease over diagnosis and over treatment of prostate cancer due to limitations of prostate-specific antigen. Recently, molecular biomarkers have shown promising results for diagnosis and prognosis of prostate cancer. Molecular biomarkers have improved the sensitivity and specificity of prostate-specific antigen and studies are ongoing to identify molecular biomarkers as a replacement for prostate-specific antigen. This review aims to give an overview of emerging molecular biomarkers for diagnosis and prognosis of prostate cancer.

Introduction: Lymphangiomatous polyp of the tonsil is generally accepted as a hamartomatous lesion. Its differential diagnosis includes fibroepithelial polyp, squamous papilloma, angiofibroma, haemangioma, arteriovenous malformation, hamartoma and lymphangioma.

Case report: A 33-year-old man presented with 2 months history of feeling of foreign body sensation in the throat. Examination revealed a nodular red coloured polyp on the left tonsil. Histologically, the polyp was covered by squamous epithelium and is composed of numerous vascular channels containing lymphocytes and eosinophilic material, in a fibrous stroma. Immunohistochemically, the endothelial cells were positive toward CD31 and D2-40.

Discussion: The characteristic histological features of a lymphangiomatous polyp are benign vascular proliferation with variable fibrous, adipose and lymphoid stromal components. Nested intraepithelial epidermotropism of lymphocytes can be observed. The vascular channels are typically thin-walled and contain eosinophilic proteinaceous material and lymphocytes. There is no reported incidence of recurrent or malignant transformation.

Introduction: Inappropriate use of blood and blood products has been well reported from many countries including Malaysia and may be due to a deficit of transfusion medicine (TM) knowledge. This study is aimed to assess TM knowledge among clinicians in a tertiary hospital.

Materials and methods: The validated exam developed by the BEST collaborative group was used to assess TM knowledge of doctors, from junior residents up to senior specialists. Scores of 42%, 62%, and 82%, corresponding to basic, intermediate, and expert levels of knowledge, respectively. Convenience sampling was done from eight blood-using departments at University Malaya Medical Centre. The Kruskal-Wallis test was used to compare the candidates' exam scores between different variables.

Results: A total of 184 doctors were assessed. The overall mean score was 40.1% (SD 12.7%). The most senior doctors had a significantly lower mean score compared with resident trainees and specialists. Doctors from haematology, anesthesiology, and internal medicine had significantly higher scores (51%, 47.4%, and 46.4% respectively, p<0.05). No correlations were found between the exam scores and the self-reported amount, or quality of prior TM teaching, nor with the year of postgraduate training. Participants did poorly on questions related to transfusion reactions, especially the question on transfusion-related acute lung injury.

Conclusion: Inadequate transfusion medicine knowledge was found across all the departments and levels of appointment. It is concerning that the most senior decision-making doctors had especially poor knowledge. TM training is needed by all residents, and regular updates should be given to established specialists.

Background: Ubiquitously Transcribed Tetracopeptide Repeat on X Chromosome (UTX) and Jumonji Domain-Containing Protein 3 (JMJD3) are histone H3 lysine 27 (H3K27) demethylases that are found to play tumour suppressor or oncogenic roles in many cancers. However, their roles in urothelial carcinoma (UC) have not been well studied.

Objective: This study investigated UTX and JMJD3 protein expression patterns in UC and assess their clinical significance.

Patients and methods: Immunohistochemistry (IHC) method was performed on formalin-fixed paraffin-embedded (FFPE) of UC tissues and compared to the normal bladder tissues from the autopsy specimen. The staining intensity of FFPE tissues were captured with the nuclear and overall positive pixels quantified using Aperio ImageScope software.

Results: JMJD3 protein uptake was present in both nucleus and cytoplasm but UTX protein was predominantly seen in the cytoplasm of UC tissue. UTX was under expressed whereas JMJD3 was over expressed in UC compared to normal bladder. UTX and JMJD3 were not related to clinical stage and grade. However, significant association between JMJD3 expression and invasiveness of tumour (p<0.05) was noted, especially in MIBC group (88.9%). UTX and JMJD3 did not yield any significance as prognostic factors for diseasespecific survival.

Conclusions: Low expression of UTX protein in UC may indicate possible loss of its tumour suppressor activity and higher JMJD3 protein expression may indicate oncogenic activity. Hence, JMJD3 protein could be a potential diagnostic biomarker in detecting bladder UC of higher stages. Further investigation needed to study the dysregulation of this protein expression with associated gene expression.

Introduction: A 1-year-old Malay girl presented with pallor, failure to thrive and hepatosplenomegaly. Her blood was sent for thalassaemia screening and it was incidentally found that her blood appeared lipaemic.

Case report: Primary and secondary causes of hyperlipidaemia were investigated. Her blood was sent for fasting lipid profile, thyroid function test (TFT), fasting plasma glucose (FPG), liver function test (LFT), renal profile (RP) and HIV screening. Lipaemic interference was removed by high-speed centrifugation. She is a product of non-consanguineous marriage. She is staying together with her stepfather who is HIV positive. Her mother's infective status was negative with no dyslipidaemic features and a normal lipid profile. Lipid profile of her biological father was not known. No other lipid stigmata such as eruptive xanthoma or lipaemia retinalis was seen in the patient. Haemoglobin analysis showed Hb E-Beta thalassaemia major. Her triglycerides was 9.05 mmol/L with normal total cholesterol, 2.85 mmol/L and high-density lipoprotein cholesterol (HDL-c), 0.26 mmol/L. Calculated low-density lipoprotein cholesterol (LDL-c) was invalid as triglycerides was >4.5 mmol/L. TFT, RP, FPG, LFT were normal and HIV status was negative. She was transfused with 10 ml/kg packed cell and her blood post transfusion appeared non lipaemic.

Conclusion: Primary hypertriglyceridaemia was excluded based on insignificant family history of dyslipidaemia. Secondary causes of hypertriglyceridaemia were ruled out based on unremarkable laboratory investigations. Thus, we conclude that this patient is having hypertriglyceridaemia thalassaemia syndrome (HTS) which is a rare disorder with unknown pathogenesis. Further research may be required to explore this unknown association.

Introduction: Oral candidiasis is one of the most common fungal infections that has been widely reported around the world. In Malaysia, the available studies for this infection are scarce.

Materials and methods: This is a 20-year retrospective study aimed to investigate the prevalence, demographic characteristics, clinical presentations, and the association of oral candidiasis with clinical parameters in oral candidiasis cases reported in the Faculty of Dentistry, Universiti Malaya from 1999 until 2019. A total of 12,964 histopathological records from the Oral Pathology Diagnostic and Research Laboratory (OPDRL) between 1999 to 2019 were retrieved. Oral candidiasis cases were selected according to the inclusion and exclusion criteria. Information of interest was obtained and analysed.

Results: From the total records retrieved, 378 oral candidiasis cases were recorded and 82.8% were diagnosed from smear test. This study showed that oral candidiasis was predominantly reported in female (64.2%) and Indian population (64.2%). The peak incidence was in the sixth decades of life (27.0%). The most commonly affected site was tongue and coated tongue was the most common clinical presentation. More than 50% of the cases had comorbidity and 10.6% were associated with dentures. Ethnicity and site of occurrence were significantly associated (p<0.05) with oral candidiasis.

Conclusion: This is the first large-scale study of oral candidiasis cases in Malaysia. The findings of this study are useful for clinical assessment of patients suspected of oral candidiasis.