AIM: For studies done in Malaysia, to identity the sample sizes and heterogeneity present in the various studies which used p16 in evaluating lesions of the cervix. To evaluate if it would be possible for a single study to answer the various questions posed by the original authors. To highlight areas where the design features of future studies can be optimised.
MATERIALS AND METHODS: Various databases were searched using synonyms for p16 AND cervix AND Malaysia. These were assessed for broad conformity to a Diagnostic Test Accuracy format. Methodological and clinical heterogeneity indicators were extracted into standardised fields.
RESULTS: There were 5 studies eligible for inclusion. Each sought to study different aspects of the disease such as diagnostic grade stratification and pathogenesis. The study type broadly conformed to a Diagnostic Test Accuracy format. The study design used was either consecutive or non-consecutive. Sample size ranged from 75 to 201. Clinical heterogeneity was present in the choice of controls with some using normal and some using inflamed tissue. Methodological heterogeneity in applying the reference test, index test and different antibody clones were present.
CONCLUSION: There was both clinical and methodological heterogeneity making synthesis of studies difficult. It is possible to design a study which would be able to answer all the questions posed by the original authors with internal validity while at the same time increasing sample size.
MATERIALS AND METHODS: We retrospectively studied CD56 expression in 54 benign and 54 malignant thyroid lesions using archival formalin fixed paraffin-embedded tissue blocks for the study period from January 2010 to December 2015, diagnosed in a tertiary hospital.
RESULTS: CD56 was expressed in 52/54 (96.3%) of benign specimens and only 24/54 (44.4%) of malignant ones. The malignant specimens comprised 31 (57.4%) papillary thyroid carcinomas (PTC), 11 (20.3%) follicular carcinomas (FC), seven (13%) medullary thyroid carcinomas (MC), one (1.9%) poorly differentiated carcinoma (PC) and four (7.4%) anaplastic carcinomas (AC). CD56 was not expressed in 28/31 (90.3%) of the PTCs, 1/11 (9.1%) FCs, 1/4 (25%) of ACs while all MCs and the PD were positive. The benign group comprised nodular hyperplasias (29/54), lymphocytic thyroiditis (10/54), follicular adenomas (FA) (14/54) and one hyalinising trabecular tumour. CD56 was expressed in all the benign cases except one FA and one nodular hyperplasia. Thirteen of the 14 FAs were CD56 positive. The difference in expression between benign and malignant tumours was statistically significant as the p value was <0.01.
CONCLUSION: CD56 is a potentially good immunohistochemical marker for differentiating papillary thyroid carcinoma from other benign follicular lesions of the thyroid especially in differentiating follicular variant PTC from FA in equivocal cases.
MATERIALS AND METHODS: A literature search was performed to identify potential miRNAs involved in the pathogenesis of HCC. Unpaired serum and ascitic fluid were obtained from 52 patients with NASH related liver cirrhosis (n=26 for each group of with and without HCC). Exosomal miRNA was isolated from all samples. Expression levels of miR-182, miR-301a and miR- 373 were determined using quantitative real-time PCR.
RESULTS: Serum-derived exosomal mir-182, miR-301a and miR-373 were significantly up-regulated with fold change of 1.77, 2.52, and 1.67 (p< 0.05) respectively in NASH-induced liver cirrhosis with HCC as compared to NASH-induced liver cirrhosis without HCC. We identified the expression levels of ascitic fluid-derived exosomal mir-182, miR-301a, and miR-373 were significantly up-regulated with fold change of 1.6, 1.94 and 2.13 respectively in NASH-induced liver cirrhosis with HCC as compared to NASH-induced liver cirrhosis without HCC (p <0.05). There was poor correlation expression of all the selected exosomal miRNA between serum- and ascitic fluid-derived in HCC group.
CONCLUSIONS: This preliminary data showed significant increase in the expression levels of exosomal miR-182, miR-301a and miR- 373 in both serum and ascetic fluid suggesting the possible roles of these miRNAs as circulating biomarkers for NASH-induced liver cirrhosis with hepatocellular carcinoma.
METHODS AND RESULTS: Analysis of publicly available DLBCL microarray data sets showed that TRPM4 transcripts were up-regulated in DLBCL compared to normal germinal centre B (GCB) cells, were expressed more highly in the activated B cell-like DLBCL (ABC-DLBCL) subtype and higher TRPM4 transcripts conferred worse overall survival (OS) in R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-treated DLBCL cases (P < 0.05). Our immunohistochemical analysis showed that TRPM4 was expressed in various human tissues but not in normal B cells within lymphoid tissues (reactive tonsil, lymph node and appendix). TRPM4 protein was present in 26% (n = 49 of 189) of our cohort of R-CHOP-treated DLBCL cases and this was associated significantly with more aggressive clinical parameters, including higher lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group (ECOG) scores or stage (P < 0.01 for each of the parameters) and the ABC-DLBCL subtype (P = 0.016). TRPM4 positivity conferred significantly worse OS (P = 0.004) and progression-free survival (PFS) (P = 0.005). Worse OS remained associated significantly with TRPM4 positivity in multivariate analysis, including higher International Prognostic Index (IPI) or the non-GCB DLBCL phenotype (P < 0.05).
CONCLUSIONS: TRPM4 protein expression is up-regulated in DLBCL cases compared to non-malignant B cells with preferential expression in ABC-DLBCL cases, and it confers significantly poorer DLBCL patient outcomes.