Displaying publications 41 - 60 of 93 in total

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  1. Fulltext Oral cancer prognosis based on clinicopathologic and genomic markers using a hybrid of feature selection and machine learning methods
    Chang SW, Abdul-Kareem S, Merican AF, Zain RB
    BMC Bioinformatics, 2013;14:170.
    PMID: 23725313 DOI: 10.1186/1471-2105-14-170
    Machine learning techniques are becoming useful as an alternative approach to conventional medical diagnosis or prognosis as they are good for handling noisy and incomplete data, and significant results can be attained despite a small sample size. Traditionally, clinicians make prognostic decisions based on clinicopathologic markers. However, it is not easy for the most skilful clinician to come out with an accurate prognosis by using these markers alone. Thus, there is a need to use genomic markers to improve the accuracy of prognosis. The main aim of this research is to apply a hybrid of feature selection and machine learning methods in oral cancer prognosis based on the parameters of the correlation of clinicopathologic and genomic markers.
    Matched MeSH terms: Biomarkers, Tumor/analysis*
  2. Quantification of Her-2/Neu gene in breast cancer patients using real time-polymerase chain reaction (Q-PCR) and correlation with immunohistochemistry findings
    Abdul Murad NA, Razak ZA, Hussain RM, Syed Hussain SN, Ko Ching Huat C, Che Md Ali SA, et al.
    Asian Pac J Cancer Prev, 2013;14(3):1655-9.
    PMID: 23679251
    BACKGROUND: HER-2/neu is a proto-oncogene that encodes a transmembrane tyrosine kinase growth factor which is crucial for stimulating growth and cellular motility. Overexpression of HER-2/neu is observed in 10-35% of human breast cancers and is associated with pathogenesis, prognosis as well as response to therapy. Given the imperative role of HER-2/neu overexpression in breast cancer, it is important to determine the magnitude of amplification which may facilitate a better prognosis as well as personalized therapy in affected patients. In this study, we determined HER-2/neu protein expression by immunohistochemistry (IHC) concurrently with HER-2/neu DNA amplification by quantitative real time-polymerase chain reaction (Q-PCR).

    MATERIALS AND METHODS: A total of 53 paired tissue samples from breast cancer patients were frozen-sectioned to characterize the tumour and normal tissues. Only tissues with 80% tumour cells were used in this study. For confirmation, Q-PCR was used to determine the HER-2/neu DNA amplification.

    RESULTS: We found 20/53 (37.7%) of the tumour tissues to be positive for HER-2/neu protein overexpression using IHC. Out of these twenty, only 9/53 (17%) cases were in agreement with the Q-PCR results. The concordance rate between IHC and Q-PCR was 79.3%. Approximately 20.7% of positive IHC cases showed no HER-2/neu gene amplification using Q-PCR.

    CONCLUSION: In conclusion, IHC can be used as an initial screening method for detection of the HER-2/neu protein overexpression. Techniques such as Q-PCR should be employed to verify the IHC results for uncertain cases as well as determination of HER-2/neu gene amplification.

    Matched MeSH terms: Biomarkers, Tumor/analysis*
  3. The immunohistochemistry signature of mismatch repair (MMR) proteins in a multiethnic Asian cohort with endometrial carcinoma
    Woo YL, Cheah PL, Shahruddin SI, Omar SZ, Arends M
    Int J Gynecol Pathol, 2014 Nov;33(6):554-9.
    PMID: 25272293 DOI: 10.1097/PGP.0000000000000099
    Endometrial cancer is the most common gynecologic cancer in developed countries and is rising in incidence globally. Although the 5-year survival rates are >80%, factors beyond conventional pathologic features that predict clinical outcomes are still being elucidated. The aims of this study were to define the prevalence and associations of deficient mismatch repair (dMMR) protein expression (MLH1, MSH2, MSH6, PMS2) by immunohistochemistry in a multiethnic Southeast Asian cohort with endometrioid endometrial cancer. A total of 77 patients with adequate formalin-fixed paraffin-embedded specimens were identified. The sections were stained in 2 centers for 4 MMR proteins and examined by 2 independent specialist histopathologists. The mean age for the cohort was 58.6 yr, with 19.4% (15/77) of patients' cancers showing loss of 2 MMR proteins. All 13 cancers with absent MLH1 showed PMS2 loss (13/15), whereas absent MSH2 correlated with MHS6 loss (2/15). There were no significant differences for dMMR cases in age, body mass index, histopathologic characteristics, and clinical outcomes. In dMMR cases, an overrepresentation of patients of Indian ethnic origin was observed compared with Chinese and Malays. These findings suggest that dMMR protein expression in a Southeast Asian endometrial cancer cohort does not correlate with disease outcomes.
    Matched MeSH terms: Biomarkers, Tumor/analysis*
  4. Aberrant proteins featured in the saliva of habitual betel quid chewers: an indication of early oral premalignancy?
    Jessie K, Jayapalan JJ, Rahim ZH, Hashim OH
    Electrophoresis, 2014 Dec;35(24):3504-11.
    PMID: 25223738 DOI: 10.1002/elps.201400252
    Prolonged chewing of betel quid is known to cause oral diseases, including cancer. The present study was performed to screen for aberrant proteins in the saliva of habitual betel quid chewers compared to nonchewers. Saliva of female subjects (n = 10) who had been chewing betel quid for more than 20 years and nonbetel quid chewers (n = 10) of the same gender and range of age was analyzed by gel-based proteomics. Increased structural microheterogeneity of saliva haptoglobin beta chains indicated by shifts of focused spots similar to that earlier reported in patients with oral squamous cell carcinoma, and their relatively higher abundance compared to nonbetel quid chewers, were detected in saliva protein profiles of all chewers. In addition, the majority of the betel quid chewers also showed significant higher abundance of hemopexin, alpha-1B glycoprotein, alpha1-antitrypsin, complement C3, and transthyretin. These proteins had previously been associated with several different cancers. Our data demonstrated different forms of protein aberration in the saliva of betel quid chewers, which may be indicative of early oral precancerous conditions.
    Matched MeSH terms: Biomarkers, Tumor/analysis*
  5. Detection of host-specific immunogenic proteins in the saliva of patients with oral squamous cell carcinoma
    Mu AK, Chan YS, Kang SS, Azman SN, Zain RB, Chai WL, et al.
    J Immunoassay Immunochem, 2014;35(2):183-93.
    PMID: 24295181 DOI: 10.1080/15321819.2013.836535
    The main purpose of this article is to develop a new and reliable saliva-based clinical diagnostic method for the early detection of oral squamous cell carcinoma (OSCC). This study used an immunoproteomic approach which allowed the detection of immunogenic host proteins in patients' samples using pooled human antibodies. In an attempt to investigate potential biomarkers of OSCC, two-dimensional electrophoresis (2-DE) followed by immunoblotting of saliva from patients and controls were compared. The protein spots of interest were analyzed using 2-DE image analyzer and subsequently subjected to MALDI-TOF/TOF and then matched against NCBI database. The result showed that four protein clusters, namely Human Pancreatic Alpha-amylase (HPA), Human Salivary Amylase (sAA), keratin-10 (K-10), and Ga Module Complexed with Human Serum Albumin (GA-HSA), had exhibited immunoreactivity in western blot. The results are suggestive of the potential use of the differentially expressed saliva protein as tumor biomarkers for the detection of OSCC. However, further studies are recommended to validate this finding.
    Matched MeSH terms: Biomarkers, Tumor/analysis*
  6. Fulltext Increased soluble HLA-DRB1in B-cell acute lymphoblastic leukaemia
    Hassan N, Dhaliwal JS, Mohd Ibrahim H, Osman R, HIdris SZ, Lee le J, et al.
    Malays J Pathol, 2015 Aug;37(2):83-90.
    PMID: 26277663 MyJurnal
    Soluble HLA (sHLA) are potential tumour markers released in order to counter immune surveillance. sHLA-class II is less known especially in acute lymphoblastic leukaemia (ALL). This study aimed to investigate soluble, surface and allelic expression of HLA Class II (sHLA-DR) in B-cell ALL patients and compare with soluble expression in normal individuals. A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to measure soluble HLA-DRB1 in plasma. Flow cytometric analysis was performed to determine median fluorescence intensity in HLA-DR surface expression. HLA-DNA typing by polymerase chain reaction, sequence specific oligonucleotides, PCRSSO was performed to determine HLA-DRB1 type in ALL samples. Results showed sHLA-DRB1 (mean±SEM) was significantly increased (p=0.001) in plasma of ALL patients (0.260 ±0.057 μg/mL; n=30) compared to healthy controls (0.051 ± 0.007µg/mL; n=31) of Malay ethnicity. However, these levels did not correlate with percentage or median fluorescence intensity of HLA-DR expressed on leukemia blasts (CD19+CD34 ± CD45(lo)HLA-DR+) or in the normal B cell population (CD19+CD34- CD45(hi)HLA-DR+) of patients. No significant difference was observed in gender (male/female) or age (paediatric/adult). Only a trend in reduced sHLA was observed in patients carrying HLA-DR04. These results have to be validated with a larger number of samples.
    Matched MeSH terms: Biomarkers, Tumor/analysis*
  7. Low HIP1R mRNA and protein expression are associated with worse survival in diffuse large B-cell lymphoma patients treated with R-CHOP
    Wong KK, Ch'ng ES, Loo SK, Husin A, Muruzabal MA, Møller MB, et al.
    Exp Mol Pathol, 2015 Dec;99(3):537-45.
    PMID: 26341140 DOI: 10.1016/j.yexmp.2015.08.019
    Huntingtin-interacting protein 1-related (HIP1R) is an endocytic protein involved in receptor trafficking, including regulating cell surface expression of receptor tyrosine kinases. We have previously shown that low HIP1R protein expression was associated with poorer survival in diffuse large B-cell lymphoma (DLBCL) patients from Denmark treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). In this multicenter study, we extend these findings and validate the prognostic and subtyping utility of HIP1R expression at both transcript and protein level. Using data mining on three independent transcriptomic datasets of DLBCL, HIP1R transcript was preferentially expressed in germinal center B-cell (GCB)-like DLBCL subtype (P<0.01 in all three datasets), and lower expression was correlated with worse overall survival (OS; P<0.01) and progression-free survival (PFS; P<0.05) in a microarray-profiled DLBCL dataset. At the protein level examined by immunohistochemistry, HIP1R expression at 30% cut-off was associated with GCB-DLBCL molecular subtype (P=0.0004; n=42), and predictive of OS (P=0.0006) and PFS (P=0.0230) in de novo DLBCL patients treated with R-CHOP (n=73). Cases with high FOXP1 and low HIP1R expression frequency (FOXP1(hi)/HIP1R(lo) phenotype) exhibited poorer OS (P=0.0038) and PFS (P=0.0134). Multivariate analysis showed that HIP1R<30% or FOXP1(hi)/HIP1R(lo) subgroup of patients exhibited inferior OS and PFS (P<0.05) independently of the International Prognostic Index. We conclude that HIP1R expression is strongly indicative of survival when utilized on its own or in combination with FOXP1, and the molecule is potentially applicable for subtyping of DLBCL cases.
    Matched MeSH terms: Biomarkers, Tumor/analysis*
  8. Overexpression of DNA methyltransferase 1 (DNMT1) protein in astrocytic tumour and its correlation with O6-methylguanine-DNA methyltransferase (MGMT) expression
    Rahman WF, Rahman KS, Nafi SN, Fauzi MH, Jaafar H
    Int J Clin Exp Pathol, 2015;8(6):6095-106.
    PMID: 26261487
    The relationship between DNA methyltransferase (DNMT) and O6-methylguanine-DNA methyltransferase (MGMT) in mediating tumorigenesis is still poorly understood. This study was carried out to investigate a correlation between DNMT1 and MGMT immunoexpression in astrocytic tumour samples.
    Matched MeSH terms: Biomarkers, Tumor/analysis*
  9. Berberis vulgaris fruit crude extract as a novel anti-leukaemic agent
    Saedi TA, Ghafourian S, Jafarlou M, Sabariah MN, Ismail P, Eusni RM, et al.
    J Biol Regul Homeost Agents, 2015 Apr-Jun;29(2):395-9.
    PMID: 26122228
    Tumor protein p53 encoded by the TP53 gene in humans is known as a cancer biomarker in patients diagnosed with cancer, and it plays an essential role in apoptosis, genomic stability, and inhibition of angiogenesis. Cancer therapies with common chemotherapy methods are effective, as known, but have some side effects. Berberis vulgaris is traditionally administrated as a cancer drug. The current research aims to evaluate p53 as a biomarker in WEHI-3 cell line and to demonstrate the Berberis vulgaris fruit crude extract (BVFCE) as a new anticancer drug. For this purpose, we evaluated the effect of BVFCE in different concentrations against WEHI-3cell line in vitro and determined the quantitative level of p53 gene in the treated WEHI-3 cells. The results demonstrated that even at only 1 mg/ml concentration of Berberis vulgaris crude extract, there was a low level of p53 biomarker expression on WEHI-3 cells in comparison with doxorubicin. Therefore, the current study suggests BVFCE as a reliable anti-leukaemic drug and candidate for anticancer therapy. However, further investigation need be carried out to confirm its efficiency in vivo.
    Matched MeSH terms: Biomarkers, Tumor/analysis
  10. Transducer-like enhancer of split 1 (TLE1) expression as a diagnostic immunohistochemical marker for synovial sarcoma and its association with morphological features
    Bakrin IH, Hussain FA, Tuan Sharif SE
    Malays J Pathol, 2016 Aug;38(2):117-22.
    PMID: 27568668 MyJurnal
    Synovial sarcoma (SS) is a malignant soft tissue tumour of uncertain histogenesis which is defined by the translocation t(X;18) that produces the fusion oncogenes SYT-SSX. The emergence of transducer-like enhancer of split 1 (TLE1) as a new immunohistochemical (IHC) marker for SS has offered an alternative to pathologists in differentiating SS from other histological mimics, especially in the setting of limited molecular facilities. We investigated the utility of IHC TLE1 expression against histomorphological features and other IHC markers in SS and non-SS tumours. Twenty-six cases of histologically diagnosed SS and 7 non-SS (for which SS was in the differential diagnosis) were subjected to TLE1 IHC staining, which was graded from 0 to 3+. Of the 26 SS cases, 12 each were biphasic and monophasic types and 2 were poorly-differentiated. TLE1 was expressed in 22/26 (84.6%) SS cases, of which 11/12 (91.7%) were biphasic, 10/12 (83.3%) monophasic and 1/2 (50%) poorly-differentiated tumours. Two of 7 (28.6%) non-SS cases were positive for TLE1. Immunopositivity of SS and non-SS cases for EMA were 20/26 (76.9%) and 2/7 (28.6%) respectively and for CK7 were 7/26 (26.9%) and 0/7 (0%) respectively. All cases were negative for CD34. Consistent histomorphological features for SS included mild nuclear pleomorphism, alternating tumour cellularity, fascicular growth pattern and thick ropy stromal collagen. In conclusion, TLE1 is not a stand-alone diagnostic IHC marker for SS. However, in the absence of molecular studies, it can contribute added diagnostic value in combination with morphological evaluation and other IHC markers such as EMA and CD34.
    Matched MeSH terms: Biomarkers, Tumor/analysis*
  11. P16INK4a: a potential diagnostic adjunct for prediction of high-grade cervical lesions in liquid-based cytology: with HPV testing and histological correlation
    Wong YP, Abdul Raub SH, Mohd Dali AZ, Kassim F, Visvalingam V, Zakaria Z, et al.
    Malays J Pathol, 2016 Aug;38(2):93-101.
    PMID: 27568665
    Human papillomavirus (HPV) is a necessary cause of cervical cancer and its precursors. Increased expression of high-risk hrHPV viral oncogenes in abnormal cells might increase the expression of p16INK4a. We aimed to determine the role of p16INK4a in detecting hrHPV-transformed epithelial cells in liquid-based cervical cytology, and compared the results with hrHPV DNA testing by realtime polymerase chain reaction (RT-PCR). Fifty-seven cytological samples were tested for p16INK4a immunomarker and hrHPV DNA. Test performance of both tests was determined by comparing sensitivity, specificity and predictive values using available histological follow-up data as gold standard. Of 57 samples, 36 (63.2%) showed immunoreactivity for p16INK4a and 43 (75.4%) were hrHPV-infected. A fairly low concordance rate (k = 0.504) between p16INK4a immunolabelling and hrHPV DNA status was noted. For prediction of cervical intraepithelial neoplasia (CIN) II and worse lesions, p16INK4a had a sensitivity and specificity of 93.5% and 60%; whereas hrHPV DNA testing had a sensitivity and specificity of 100% and 20%. Dual testing by combining p16INK4a and hrHPV showed sensitivity and specificity of 100% and 33.3%. In conclusion, p16INK4a is useful in predicting severity of the cytological abnormalities. Although p16INK4a is more specific but less sensitive than hrHPV in detecting high-grade cervical lesions, a combination of both tests failed to demonstrate significant improvement in diagnostic sensitivity, specificity and predictive value. Larger-scale prospective studies are required to assess further whether this biomarker should be routinely used as primary screening tool independently or in combination with hrHPV testing to improve diagnostic accuracy in cervical cytology.
    Matched MeSH terms: Biomarkers, Tumor/analysis*
  12. Primary mediastinal large B-cell lymphoma and its mimickers: a rare case report with literature review
    Win TT, Kamaludin Z, Husin A
    Malays J Pathol, 2016 Aug;38(2):153-7.
    PMID: 27568673 MyJurnal
    Primary mediastinal large B-cell lymphoma (PMLBL) is an uncommon non-Hodgkin lymphoma with a distinct clinicopathological entity in the WHO classification of lymphoid malignancies. It is known to originate from B-cells of the thymus. It mimics thymic neoplasms and other lymphomas clinically and histopathologically. We reported a 33-year-old obese man who presented with shortness of breath off and on for 4 years. Radiologically, there was a huge anterior mediastinal mass. Tru-cut biopsy was initially diagnosed as type-A thymoma. Histopathological examination of the excised specimen revealed PMLBL with stromal fibrosis and sclerosis which created a diagnostic difficulty. The neoplastic cells varied from medium-sized to large pleomorphic cells, including mononuclear cells with centroblastic and immunoblastic features as well as bi-lobed Reed Sternberg (RS)-like cells and horse-shoe like hallmark cells. Some interlacing spindle cells and epithelioid cells were also present. Immunohistochemically, tumour cells expressed diffuse positivity for LCA, CD20, CD79a, CD23, Bcl2, MUM-1 and heterogenous positivity for CD30 and EMA, and were negative for CD10, CD15 and ALK. Ki67 scoring was very high. Tumour cells infiltrated into peri-thymic fat and pericardium. No malignant cells were detected in the pleural fluid and there was no bone marrow infiltration. The patient showed partial response to 6 cycles of RICE chemotherapy, and was planned for second line chemotherapy using hyper-CVAD regimen followed by autologous stem cell transplantation. This case illustrates the importance of thorough sampling and immunohistochemistry in differentiating PMLBL from its differential diagnoses.
    Matched MeSH terms: Biomarkers, Tumor/analysis
  13. Estrogen receptor β in Merkel cell carcinoma: its possible roles in pathogenesis
    Azmahani A, Nakamura Y, Ishida H, McNamara KM, Fujimura T, Haga T, et al.
    Hum Pathol, 2016 10;56:128-33.
    PMID: 27343835 DOI: 10.1016/j.humpath.2016.06.005
    Sex steroids have been postulated to influence skin development and functions as well as its pathogenesis. MCC occurs in both sexes; however, the specific differences in pathogenesis among sexes have yet to be conclusively defined. The detailed status of sex steroid receptors (AR, PRA and PRB, and ERα, ERβ) are also unknown in MCC patients. We first immunolocalized sex steroid receptors and compared the results with immunolocalization of relevant transcription factors including SOX2, FOXA1, and Bcl-2 and Ki-67 in 18 cases of MCCs. AR, PRA, PRB, ERα, ERβ, Bcl-2, SOX2, and FOXA1 immunoreactivity was evaluated by using the modified H score method, and Ki-67 was quantified using labeling index. ERβ immunoreactivity was markedly present in all the cases of MCC examined, with relatively weak immunoreactivity of ERα, AR, PRA, and PRB. The status of ERβ immunoreactivity was also significantly correlated with Ki-67 labeling index and Bcl-2 score. These results demonstrated that ERβ could be associated with regulation of both cell proliferation and apoptosis in MCCs.
    Matched MeSH terms: Biomarkers, Tumor/analysis*
  14. Fulltext Glypican-3 is useful but not superior to Hep Par 1 in differentiating hepatocellular carcinoma from other liver tumours
    Pour AM, Masir N, Rose IM
    Malays J Pathol, 2016 Dec;38(3):229-233.
    PMID: 28028292 MyJurnal
    To assess the diagnostic utility of glypican-3 (GPC-3) in comparison to Hep Par 1 in the diagnosis of liver tumours, a cross-sectional study involving 66 resected liver tumours were tested for the protein expression of these markers by immunohistochemistry using monoclonal antibodies. Of the 66 cases, 26 (39.4%) were hepatocellular carcinoma (HCC), 4 (6.1%) were intrahepatic cholangiocarcinoma and 36 (54.5%) were metastatic tumours. Hep Par 1 and GPC-3 expressions in HCC were 24/26 (92.3%) and 19/26 (73.1%) respectively. In contrast, of non-HCC cases, only 2/40 cases (5.0%) expressed Hep Par 1, including a metastatic colorectal adenocarcinoma and a metastatic gastric adenocarcinoma. GPC-3 was expressed in 3/40 cases (7.5%), i.e. a metastatic adenocarcinoma of unknown origin, a metastatic gastric adenocarcinoma and an intrahepatic cholangiocarcinoma. The sensitivity and specificity for Hep Par 1 were 92.3% and 95% respectively while that of GPC-3 was 73.1% and 92.5% respectively. GPC-3 is a useful marker in the diagnosis of HCC. However it is not superior to Hep Par 1 in its sensitivity and specificity. We recommend that it is utilized together with Hep Par 1 as a panel in the diagnosis of HCC.
    Matched MeSH terms: Biomarkers, Tumor/analysis
  15. Fulltext Histomorphology and Immunohistochemistry of Gastrointestinal Stromal Tumors in a Malaysian Population
    Kkrishnappa P, Loh EJ, Mohamad IB, Tata MD, Akhilesh M, Palayan K
    Asian Pac J Cancer Prev, 2016;17(6):2795-9.
    PMID: 27356692
    PURPOSE: To study histomorphological and immunohistochemical patterns of gastro-intestinal stromal tumours (GISTs) in Malaysia.

    MATERIALS AND METHODS: A total of 29 GIST cases from Hospital Tuanku Ja'afar, Seremban ,were studied retrospectively over a period of 10 years from January 2002 to December 2011. Patient demographic data like age, sex and etnicity were collected. Tumour characteristics like site, maximum dimension and specimen type were analysed. Evaluation was according to established criteria into very low, low, intermediate and high-risk categories. Immunohistochemical characteristics were also analysed.

    RESULTS: The mean age of patients was 59.7 years. Males (59%) were found to be more commonly affected than females (41%). The Chinese (45%) were commonly affected than Malays (41%), and Indians (10%). The most common symptom was pain in the abdomen (13.8%). More than half of the cases were seen in stomach (53%). The tumour size ranged from 1.5 cm to 17 cm with a mean of 6.94cm. Microscopic findings revealed that the spindle cell type was the most common (76%). It was observed that the majority of the cases (48%) were categorised in the intermediate risk group. Immunohistochemical staining showed positivity for CD117 (78.6%), CD34 (71.4%), vimentin (86.2%), S-100 (27.6%), SMA (35.7%), PKC THETA (46.4%) and PDGRFA (67.9%).
    Matched MeSH terms: Biomarkers, Tumor/analysis*
  16. The oral microbiome community variations associated with normal, potentially malignant disorders and malignant lesions of the oral cavity
    Mok SF, Karuthan C, Cheah YK, Ngeow WC, Rosnah Z, Yap SF, et al.
    Malays J Pathol, 2017 Apr;39(1):1-15.
    PMID: 28413200 MyJurnal
    The human oral microbiome has been known to show strong association with various oral diseases including oral cancer. This study attempts to characterize the community variations between normal, oral potentially malignant disorders (OPMD) and cancer associated microbiota using 16S rDNA sequencing. Swab samples were collected from three groups (normal, OPMD and oral cancer) with nine subjects from each group. Bacteria genomic DNA was isolated in which full length 16S rDNA were amplified and used for cloned library sequencing. 16S rDNA sequences were processed and analysed with MOTHUR. A core oral microbiome was identified consisting of Firmicutes, Proteobacteria, Fusobacteria, Bacteroidetes and Actinobacteria at the phylum level while Streptococcus, Veillonella, Gemella, Granulicatella, Neisseria, Haemophilus, Selenomonas, Fusobacterium, Leptotrichia, Prevotella, Porphyromonas and Lachnoanaerobaculum were detected at the genus level. Firmicutes and Streptococcus were the predominant phylum and genus respectively. Potential oral microbiome memberships unique to normal, OPMD and oral cancer oral cavities were also identified. Analysis of Molecular Variance (AMOVA) showed a significant difference between the normal and the cancer associated oral microbiota but not between the OPMD and the other two groups. However, 2D NMDS showed an overlapping of the OPMD associated oral microbiome between the normal and cancer groups. These findings indicated that oral microbes could be potential biomarkers to distinguish between normal, OPMD and cancer subjects.
    Matched MeSH terms: Biomarkers, Tumor/analysis
  17. Differential diagnostic significance of HBME-1, CK19 and S100 in various thyroid lesions
    Palo S, Biligi DS
    Malays J Pathol, 2017 Apr;39(1):55-67.
    PMID: 28413206
    OBJECTIVE: Due several overlapping histomorphological features and pitfalls in thyroid pathology, there is need to establish a panel of immunomarkers that would aid in proper diagnosis. This study was carried out to investigate the ability of HBME-1, CK19, and S100 in differentiating between hyperplastic, benign and malignant thyroid lesions.

    MATERIALS AND METHODS: Immunohistochemical analysis of 60 thyroidectomy specimens (10 hyperplastic nodules, 14 follicular adenomas and 36 malignant thyroid neoplasms) was carried out. The extent and intensity of HBME-1, CK19, and S100 immunoreactivity was assessed in each case.

    RESULTS: HBME-1 positivity was noted in 86.1% of malignant cases while the majority of the benign lesions were negative. Diffuse strong CK19 positivity was documented in 27/31 papillary carcinoma whereas all cases of follicular carcinoma and medullary carcinoma were negative. Most of the hyperplastic nodules and follicular adenomas were also CK19 negative, although focal weak staining was noted in a few cases. S100 was positive only in medullary carcinoma. HBME-1 was most sensitive (86.1%) and specific (87.5%) in distinguishing between benign and malignant thyroid lesions. The diagnostic accuracy was further increased when HBME-1 was used simultaneously with CK19/S100/CK19+S100. The sequential use of HBME-1 and CK19 also proved beneficial in discriminating between the various follicular-patterned thyroid lesions.

    CONCLUSION: HBME-1 immunolabeling suggests malignancy, whereas strong diffuse CK19 positivity substantiates papillary differentiation. The utilization of these markers (alone or in combination) along with histomorphological evaluation is helpful in the differential diagnosis. S100 has minimal utility in this regard.

    Matched MeSH terms: Biomarkers, Tumor/analysis*
  18. TRPM4 expression is associated with activated B cell subtype and poor survival in diffuse large B cell lymphoma
    Loo SK, Ch'ng ES, Md Salleh MS, Banham AH, Pedersen LM, Møller MB, et al.
    Histopathology, 2017 Jul;71(1):98-111.
    PMID: 28248435 DOI: 10.1111/his.13204
    AIMS: Transient receptor potential channel melastatin 4 (TRPM4) is an ion channel that regulates influx of calcium cations (Ca2+ ). Recent studies suggest that TRPM4 is an oncoprotein, and its up-regulated transcript level has been reported in diffuse large B cell lymphoma (DLBCL). We aimed to investigate TRPM4 protein expression pattern in non-malignant tissues and DLBCL cases, and its association with clinico-demographic parameters and survival in DLBCL.

    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.

    Matched MeSH terms: Biomarkers, Tumor/analysis*
  19. p40 in metastatic pulmonary trophoblastic tumour: potential diagnostic pitfall on histopathology
    Vallonthaiel AG, Walia R, Pramanik R, Sharma MC, Jain D
    Malays J Pathol, 2017 Aug;39(2):175-179.
    PMID: 28866701
    p40, one of the two isomers of p63, is nowadays widely used for diagnosis of squamous cell carcinoma, especially in subtyping non-small cell carcinoma on lung biopsies. We describe a case in which lung tumour was misdiagnosed as squamous cell carcinoma due to p40 immunopositivity. A 36-year-old lady presented with cough and left sided chest pain of 2 months duration. Chest imaging revealed a lesion in left lower lobe of the lung and biopsy was suggestive of squamous cell carcinoma. However, past history revealed amputation of great toe for non-healing discharging ulcer which on histopathology was diagnosed as choriocarcinoma. She also had a history of hysterectomy five years ago, details of which were not available. Post-amputation β-hCG levels were high and she had been treated with multimodality chemotherapy for choriocarcinoma. She had good response to chemotherapy initially, however became resistant later on. Review of the lung biopsy in the light of the past history along with extensive literature review led to the final diagnosis of metastatic trophoblastic tumour to lung. Hence, awareness that p40 immunopositivity can be seen in trophoblastic tumours is essential to avoid misdiagnosis, especially in sites like the lung where squamous cell carcinoma is common.
    Matched MeSH terms: Biomarkers, Tumor/analysis
  20. Adult primary medullary carcinoma: an unusual cause of pain from intussusception
    Chuah YY, Lee YY, Shih CA
    Br J Hosp Med (Lond), 2017 Aug 02;78(8):474.
    PMID: 28783396 DOI: 10.12968/hmed.2017.78.8.474
    Matched MeSH terms: Biomarkers, Tumor/analysis
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