Displaying publications 1 - 20 of 66 in total

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  1. Wong SF, Reimann K, Lai LC
    Pathology, 2001 Nov;33(4):454-9.
    PMID: 11827412
    Oestrogens play an important role in the development of breast cancer. Oestrone sulphate (E1S) acts as a huge reservoir of oestrogens in the breast and is converted to oestrone (E1) by oestrone sulphatase (E1STS). E1 is then reversibly converted to the potent oestrogen, oestradiol (E2) by oestradiol-17beta hydroxysteroid dehydrogenase (E2DH). The aim of this study was to assess the effects of transforming growth factor-beta1 (TGFbeta1), insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II) on cell growth, E1STS and E2DH activities in the MCF-7 and MDA-MB-231 human breast cancer cell lines. TGFbeta1, IGF-I and IGF-II alone or in combination inhibited cell growth of both cell lines but no additive or synergistic effects were observed. The treatments significantly stimulated E1STS activity in the MCF-7 cell line, except for TGFbeta1 alone and TGFbeta1 and IGF-I in combination, where no effects were seen. Only TGFbeta1 and IGF-II acted synergistically to stimulate E1STS activity in the MCF-7 cells. There was no significant effect on E1STS activity in the MDA-MB-231 cells with any of the treatments. In the MCF-7 cells, TGFbeta1 and IGF-I, IGF-I and IGF-II, and TGFbeta1, IGF-I and IGF-II acted synergistically to stimulate the reductive E2DH activity, while only TGFbeta1, IGF-I and IGF-II synergistically stimulated the oxidative E2DH activity. There were no additive or synergistic effects on both oxidative and reductive E2DH activities in the MDA-MB-231 cells. In conclusion, TGFbeta1, IGF-I and IGF-II may have effects on oestrogen metabolism, especially in the MCF-7 cell line where they stimulated the conversion of E1S to E1 and E1 to E2 and, thus, may have roles to play in the development of breast cancer.
    Matched MeSH terms: Breast Neoplasms/pathology; Tumor Cells, Cultured/pathology
  2. Wong SF, Lai LC
    Pathology, 2001 Feb;33(1):85-92.
    PMID: 11280615
    Transforming growth factor beta (TGFbeta) is secreted as a large latent precursor from both normal and transformed cells which needs to be activated for biological activity. The active TGFbeta binds either directly to TbetaR-II or indirectly by binding to beta-glycan which then presents the TGFbeta to TbetaR-II. Formation of the TGFbeta-TbetaR-II complex rapidly leads to phosphorylation of TbetaR-I. TbetaR-I, in turn, phosphorylates receptor-specific Smads and induces their translocation into the nucleus. TGFbeta is able to act as a growth stimulator or inhibitor and elicits a broad spectrum of biological effects on various cell types. However, these cells may lose their sensitivity and responsiveness to TGFbeta. Down-regulation or loss of functional receptors, aberrant signal transduction pathways due to Smad mutations, loss of the cell's ability to activate latent TGFbeta, loss of the peptide itself or functional genes that control the transcription and translation of TGFbeta may contribute to development of cancer.
  3. Wong MS, Chew WL, Aw TC
    Pathology, 1999 Aug;31(3):225-9.
    PMID: 10503268
    Lipoprotein(a) [Lp(a)] is formed when apolipoprotein(a) is linked to low density lipoprotein (LDL)-cholesterol via a single disulfide bond. It is an independent risk factor for myocardial infarction and raised concentrations are associated with an increased risk of developing coronary artery disease. Singapore has a multi-racial population of 77% Chinese, 14% Malays and 7% Indians. Studies have shown that the Indians have significantly higher standardised mortality ratios (SMR) compared to the Chinese and the Malays. We measured serum Lp(a) concentrations in 803 healthy individuals recruited from the Multiphasic Health Screening Programme, using the Macra Lp(a) sandwich enzyme immunoassay kit (Strategics Diagnostics, Delaware, USA). Lp(a) concentrations were skewed in all three groups. Our population mean was 9.0 mg/dl, with 50th, 75th and 95th percentile values of 10.2, 19.8 and 43.1 mg/dl, respectively, which are lower than values reported from Caucasian populations (15.0, 29.0 and 60.0 mg/dl, respectively). Males had lower Lp(a) concentrations than females (P < 0.05). The Indian group had significantly higher concentrations (median 12.3 mg/dl) compared to their Chinese (median 9.6 mg/dl) and Malay (median 8.4 mg/dl) counterparts (P < 0.05). This could partly account for the higher SMR seen in the Indian population in Singapore. As serum Lp(a) concentrations are method- and population-dependent, we recommend that laboratories determine their own reference ranges by their method to avoid misclassification of the coronary heart disease (CHD) risk of patients.
  4. Wong KT, Vadivelu J, Puthucheary SD, Tan KL
    Pathology, 1996 May;28(2):188-91.
    PMID: 8743829
    In order to assess the usefulness of immunohistochemistry in the diagnosis of melioidosis, an infection by Burkholderia pseudomallei, polyclonal antibodies were applied to tissues from known cases of melioidosis and to other infected tissues. Formalin-fixed, paraffin-embedded tissues were stained by a modified immunoperoxidase technique. In autopsy tissues with inflammatory lesions of melioidosis, the cytoplasm of phagocytes and intact bacilli, both intra- and extracellular, were stained very strongly positive. Relatively more focal positive staining was observed in some but not all surgical biopsies from proven cases of melioidosis. In granulomas staining was mainly found in the central necrotic areas, with little staining of peripheral phagocytes. All control materials stained negative. Immunohistochemistry appears to be a useful diagnostic tool in melioidosis.
    Matched MeSH terms: Melioidosis/pathology
  5. Wong KK, Prepageran N, Peh SC
    Pathology, 2009 Feb;41(2):133-9.
    PMID: 18972319 DOI: 10.1080/00313020802436790
    AIMS: To stratify upper aerodigestive tract (UAT) diffuse large B-cell lymphoma (DLBCL) into prognostic subgroups by immunohistochemical staining (IHC) method, and to evaluate the association rate of UAT DLBCL with Epstein-Barr virus (EBV).

    METHODS: Using a panel of antibodies to CD10, Bcl-6, MUM1 and CD138, consecutive cases of primary UAT DLBCL were stratified into subgroups of germinal centre B-cell-like (GCB) and non-GCB, phenotype profile patterns A, B and C, as proposed by Hans et al. and Chang et al., respectively. EBER in situ hybridisation technique was applied for the detection of EBV in the tumours.

    RESULTS: In this series of 32 cases of UAT DLBCL, 34% (11/32) were GCB, and 66% (21/32) were non-GCB types; 59% (19/32) had combined patterns A and B, and 41% (13/32) had pattern C. Statistical analysis revealed no significant difference in the occurrence of these prognostic subgroups in the UAT when compared with series of de novo DLBCL from all sites. There was also no site difference in phenotype protein expressions, with the exception of MUM1. EBER in situ hybridisation stain demonstrated only one EBV infected case.

    CONCLUSIONS: Prognostic subgroup distribution of UAT DLBCL is similar to de novo DLBCL from all sites, and EBV association is very infrequent.

    Matched MeSH terms: Otorhinolaryngologic Neoplasms/pathology; Lymphoma, Large B-Cell, Diffuse/pathology
  6. Wong HT, Mun KS, Zulkiflee AB, Prepageran N
    Pathology, 2016 Jan;48(1):95-6.
    PMID: 27020222 DOI: 10.1016/j.pathol.2015.11.022
    Matched MeSH terms: Maxillary Sinus/pathology; Maxillary Sinus Neoplasms/pathology*; Hemangioendothelioma, Epithelioid/pathology*
  7. Wong CY, Cheong SK, Mok PL, Leong CF
    Pathology, 2008 Jan;40(1):52-7.
    PMID: 18038316
    AIMS: Adult human bone marrow contains a population of mesenchymal stem cells (MSC) that contributes to the regeneration of tissues such as bone, cartilage, muscle, tendon, and fat. In recent years, it has been shown that functional stem cells exist in the adult bone marrow, and they can contribute to renal remodelling or reconstitution of injured renal glomeruli, especially mesangial cells. The purpose of this study is to examine the ability of MSC isolated from human bone marrow to differentiate into mesangial cells in glomerular injured athymic mice.

    METHODS: MSC were isolated from human bone marrow mononuclear cells based on plastic adherent properties and expanded in vitro in the culture medium. Human mesenchymal stem cells (hMSC) were characterised using microscopy, immunophenotyping, and their ability to differentiate into adipocytes, chondrocytes, and osteocytes. hMSC were then injected into athymic mice, which had induced glomerulonephropathy (GN).

    RESULTS: Test mice (induced GN and infused hMSC) were shown to have anti-human CD105(+) cells present in the kidneys and were also positive to anti-human desmin, a marker for mesangial cells. Furthermore, immunofluorescence assays also demonstrated that anti-human desmin(+) cells in the glomeruli of these test mice were in the proliferation stage, being positive to anti-human Ki-67.

    CONCLUSIONS: These findings indicate that hMSC found in renal glomeruli differentiated into mesangial cells in vivo after glomerular injury occurred.

    Matched MeSH terms: Bone Marrow Cells/pathology; Glomerulonephritis/pathology*; Kidney Glomerulus/pathology*; Mesangial Cells/pathology*; Mesenchymal Stromal Cells/pathology*
  8. Ting HY, Sthaneshwar P, Bee PC, Shanmugam H, Lim M
    Pathology, 2019 Aug;51(5):507-511.
    PMID: 31253381 DOI: 10.1016/j.pathol.2019.04.002
    Serum protein (SPE) and immunofixation electrophoresis (IFE) have been extensively validated for the routine use of identifying, characterising and quantifying monoclonal proteins. However, accurate quantitation of IgA monoclonal proteins can be difficult when they migrate in to the β fraction, due to co-migration with transferrin and complement components. The heavy/light chain (HLC) immunoassay is an additional tool for measuring intact immunoglobulin monoclonal proteins. Therefore, we aimed to examine the clinical utility of the HLC assay for the disease monitoring of IgG and IgA multiple myeloma (MM) patients. A total of 177 samples from 30 MM patients (21 IgG and 9 IgA) were analysed retrospectively with median number of six follow up samples per patient (range 3-13). Serum free light chains (sFLC) and HLC were quantified using Freelite and Hevylite immunoassays. Details of M-protein concentration, β-globulin levels, total immunoglobulin levels and disease treatment response were obtained from the laboratory and patient information system. Passing-Bablok regression analysis was performed to compare (i) M-protein quantification with involved HLC (iHLC) and (ii) total immunoglobulin with summated HLC pairs for each immunoglobulin type (e.g., IgGκ+IgGλ). For 127 IgG MM samples, IgG iHLC levels showed a good correlation with SPE quantification (iHLC y=0.96x+4.9; r=0.917) and summated HLC showed a good correlation with total IgG concentration (summated HLC y=0.94x+5.74; r=0.91). In total, 95/127 (75%) IgG MM follow-up samples had an abnormal HLC ratio and 122/127 (96%) had a positive SPE, probably due to the lower sensitivity of HLC assay in detecting clonality in patients with IgG MM. Consistent with this, one patient assigned a very good partial response by International Myeloma Working Group criteria would be assigned a complete response based on HLC measurements. For 50 IgA MM samples, 42/50 (84%) had an abnormal HLC ratio. Conversely, 50/50 (100%) of M-proteins showed β fraction migration and were difficult to accurately quantify by SPE. Therefore, M-protein concentration and iHLC did not correlate as well in IgA MM (y=1.9x-8.4; r=0.8) compared to IgG MM. However, there was good correlation between total IgA and summated IgA HLC (IgAκ+IgAλ y=1.35x-0.33; r=0.95). Of the 8/50 (16%) IgA samples with a normal HLC ratio, 6/8 (75%) were consistent with the disease status being in complete remission. Interestingly, in one IgA MM patient, SPE and IFE were negative, but the serum FLC ratio and involved FLC were highly abnormal, consistent with the presence of light chain escape. Our data suggest HLC measurements could add value to the current disease monitoring of MM patients. In IgG MM patients, the M-protein level correlated well with HLC values. The HLC assay complements the serum FLC assay and is especially useful for monitoring of IgA MM patients who display M-proteins migrating in the β region on SPE.
  9. Tay Za K, Bee PC, Shanmugam H
    Pathology, 2020 Feb;52(2):273-276.
    PMID: 31883672 DOI: 10.1016/j.pathol.2019.10.013
    Matched MeSH terms: Carcinoma/pathology*; Lung Neoplasms/pathology*
  10. Tan LP, Ng BK, Balraj P, Lim PK, Peh SC
    Pathology, 2007 Apr;39(2):228-34.
    PMID: 17454753
    BACKGROUND AND AIMS: Colorectal cancers of different subtypes involve different pathogenic pathways like the Wnt and the mutator pathways. In this study, we screened 73 colorectal cancer cases from a multi-racial group for genetic and expression profile defects with the aim of correlating these with patients' clinicopathological characteristics.
    METHODS: Mutation screening of the entire coding region of APC and exon 3 of CTNNB1, loss of heterozygosity (LOH) of APC, and microsatellite instability (MSI) status were assessed for 44 patients with available paired frozen normal and tumour tissues. In addition, 29 cases with available paraffin embedded tumour blocks were screened for mutation in exon 3 of CTNNB1, the APC mutation cluster region (codon 1286-1513), and hMLH1, hMSH2, hMSH6 protein expressions by immunohistochemistry method.
    RESULTS: In our study, 15/73 cases showed APC mutations (20.5%), 1/73 cases had CTNNB1 mutation (1.4%), 5/32 cases had APC LOH (15.6%), and 16/70 (22.9%) cases revealed at least some form of mismatch repair (MMR) defect. Tumour grade (poor differentiation) was found to correlate significantly with right-sided tumour and mucinous histology (p = 0.01879 and 0.00320, respectively). Patients of younger age (below 45 years) more often had tumours of mucinous histology (p = 0.00014), while patients of older age (above 75 years) more often had tumours on the right side of the colon (p = 0.02448). Tumours of the mucinous histology subtype often had MMR defects (p = 0.02686). There was no difference in the occurrence of APC and CTNNB1 mutations and MMR defects found within our multi-racial colorectal cancer patient cohort.
    CONCLUSION: Our findings support the notion that racial factor may not be related to the occurrence of MMR defects and APC and CTNNB1 mutations in our multi-racial patient cohort.
  11. Tan JA, Chin PS, Wong YC, Tan KL, Chan LL, George E
    Pathology, 2006 Oct;38(5):437-41.
    PMID: 17008283
    In Malaysia, about 4.5% of the Malay and Chinese populations are heterozygous carriers of beta-thalassaemia. The initial identification of rare beta-globin gene mutations by genomic sequencing will allow the development of simpler and cost-effective PCR-based techniques to complement the existing amplification refractory mutation system (ARMS) and gap-PCR used for the identification of beta-thalassaemia mutations.
    Matched MeSH terms: beta-Thalassemia/pathology
  12. Tai YC, Kim LH, Peh SC
    Pathology, 2003 Oct;35(5):436-43.
    PMID: 14555389
    AIMS: The most common recurrent genetic aberration in anaplastic large cell lymphoma (ALCL) is translocation involving the ALK gene that results in ectopic expression of ALK protein in lymphoid tissue. This study aims to investigate the frequency of ALK gene rearrangement in a series of Asian ALCL.

    METHODS: ALK gene rearrangement was detected by immunostaining of ALK protein and fluorescence in situ hybridisation (FISH) targeting at the 2p23 region.

    RESULTS: The expression of ALK protein was detected in 24/34 (71%) of the cases, and it was significantly higher in childhood cases (100%) when compared to adult cases (47%). The analyses by FISH were consistent with the results from immunostaining of ALK protein, but the analyses were only successful in 15/34 (44%) cases. FISH analyses detected extra copies of ALK gene in three cases, including one case that expressed ALK protein and showed 2p23 rearrangement.

    CONCLUSIONS: The current series revealed a high frequency of ALK gene rearrangement, especially in the children. Immunostaining of ALK protein is a reliable indication of ALK gene rearrangement, and is superior to FISH. However, FISH analysis is useful in detecting other genetic aberrations that are not related to ALK gene rearrangement.

    Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/pathology
  13. Sthaneshwar P, Shanmugam H, Swan VG, Nasurdin N, Tanggaiah K
    Pathology, 2013 06;45(4):417-9.
    PMID: 23635828 DOI: 10.1097/PAT.0b013e32836142eb
    AIM: Measurement of HbA1c provides an excellent measure of glycaemic control for diabetic patients. However, haemoglobin (Hb) variants are known to interfere with HbA1c analysis. In our laboratory HbA1c measurement is performed by Variant II turbo 2.0. The aim of this study is to investigate the influence of HbE trait on HbA1c analysis.

    METHODS: Haemoglobin variants were identified by HbA1c analysis in 93 of 3522 samples sent to our laboratory in a period of 1 month. Haemoglobin analysis identified HbE trait in 81 of 93 samples. To determine the influence of HbE trait on HbA1c analysis by Variant II Tubo 2.0, boronate affinity high performance liquid chromatography (HPLC) method (Primus PDQ) was used as the comparison method. Two stage linear regression analysis, Bland Altman plot and Deming regression analysis were performed to analyse whether the presence of HbE trait produced a statistically significant difference in the results. The total allowable error for HbA1c by the Royal Australasian College of Pathologists (RCPA) external quality assurance is 5%. Hence clinically significant difference is more than 5% at the medical decision level of 6% and 9%.

    RESULTS: Statistically and clinically significant higher results were observed in Variant II Turbo 2.0 due to the presence of HbE trait. A positive bias of ∼10% was observed at the medical decision levels.

    CONCLUSION: Laboratories should be cautious when evaluating HbA1c results in the presence of haemoglobin variants.

  14. Sthaneshwar P, Jamaluddin FA, Fan YS
    Pathology, 2010;42(5):454-6.
    PMID: 20632822 DOI: 10.3109/00313025.2010.493861
    The aim of this study was to evaluate the distribution of cardiac troponin I (cTnI) values, measured by the ADVIA TnI-Ultra method in a multi-ethnic group and to determine the imprecision of the assay.
  15. Siar CH, Ng KH
    Pathology, 2019 Aug;51(5):494-501.
    PMID: 31262562 DOI: 10.1016/j.pathol.2019.04.004
    The ameloblastoma is the most common and clinically significant odontogenic epithelial neoplasm known for its locally-invasive behaviour and high recurrence risk. Epithelial-to-mesenchymal transition (EMT) is a fundamental process whereby epithelial cells lose their epithelial characteristics and gain mesenchymal properties. EMT induction via transcription repression has been investigated in ameloblastoma. However, morphologically evident mesenchymal phenotypic transition remains ill-defined. To determine this, 24 unicystic (UA), 34 solid/multicystic (SA) and 18 recurrent ameloblastoma (RA) were immunohistochemically examined for three EMT-related mesenchymal markers, alpha smooth muscle actin (α-SMA), osteonectin and neuronal cadherin (N-cadherin). All three factors were heterogeneously detected in ameloblastoma samples (α-SMA, n=71/76, 93.4%; osteonectin, n=72/76, 94.7%; N-cadherin, n=24/76, 31.6%). In the tumoural parenchyma, immunoreactive cells were not morphologically distinct from their non-reactive cellular counterparts. Rather, α-SMA and osteonectin predominantly labelled the cytoplasm of central polyhedral > peripheral columnar/cuboidal tumour cells. N-cadherin demonstrated weak-to-moderate circumferential membranous staining in both neoplastic cell types and cytoplasmic expression in spindle-celled epithelium of desmoplastic amelobastoma. For all tumour subsets, α-SMA and osteonectin scored significantly higher in the stroma > parenchyma whilst α-SMA was overexpressed along the tumour invasive front > centre (p<0.05). Stromal N-cadherin scored higher in SA > UA and RA > UA (p<0.05). Other clinicopathological parameters showed no significant associations. Taken together, acquisition of mesenchymal traits without morphologically evident mesenchymal alteration suggests partial EMT in ameloblastoma. Stromal upregulation of these proteins in SA and RA implicates a role in local invasiveness.
    Matched MeSH terms: Ameloblastoma/pathology*; Jaw Neoplasms/pathology*; Neoplasm Invasiveness/pathology*
  16. Shaminie J, Peh SC, Tan J
    Pathology, 2005 Feb;37(1):39-44.
    PMID: 15875732
    AIM: Tumour suppressor gene p53 is a common target in carcinogenesis, reported to be altered and functionally inactive in 70% of human cancers. Although p53 mutations are less commonly present in haematological malignancies when compared with other solid tumours, they have been reported in histological transformation of follicular lymphoma. We aimed to investigate the frequency of p53 gene alterations in paraffin-embedded tissue using commercially available PCR-SSCP, and to correlate the results with P53 protein expression by immunohistochemistry.

    METHODS: Surgical samples from seven patients with a total of 17 sequential biopsies were retrieved for the study of p53 gene expression using immunohistochemical stain, and gene status by PCR-SSCP for exons 5-8. The tumours were graded according to the WHO classification criteria. P53 was distinctly over-expressed in five transformed higher grade biopsies, and all except one showed electrophoretic mobility shift in PCR-SSCP analysis. Sequencing analysis revealed single nucleotide substitutions in three of four of these high-grade transformed cases with band shift (75%), whereas some other studies reported a lower frequency of 25-30%, and mobility shift result was found to correlate with P53 expression. Lower grade tumours without P53 over-expression did not demonstrate band shift, and sequencing analysis did not reveal mutations.

    CONCLUSIONS: We demonstrated the feasibility of adopting PCR-SSCP for screening of p53 mutations in archival tissue samples in this study, and there is a strong correlation of p53 gene over-expression and mutation events in high-grade transformed tumours.

  17. Shaminie J, Peh SC, Tan MJ
    Pathology, 2003 Oct;35(5):414-21.
    PMID: 14555386
    AIMS: PCR has been the primary method used for the detection of t(14;18) translocation in formalin-fixed, paraffin-embedded tissues. This technique mainly targets the well-characterised breakpoint regions in chromosomes 14 and 18. FISH is now applicable on paraffin tissue sections and has been suggested to be capable of detecting essentially 100% of t(14;18) translocated cases. In this study, we described the application of both PCR and FISH for the detection of t(14;18) translocation.

    METHODS: Fifty follicular lymphoma cases were retrieved from the files of the Department of Pathology, University of Malaya Medical Centre (UMMC). Nested PCR amplification of MBR/JH and mcr/JH was performed in these cases, and those cases that did not demonstrate the translocation were subjected to FISH analysis.

    RESULTS: Thirty cases (60%) had t(14;18) translocation detected by PCR, 25 (50%) had breakpoint with MBR and five (10%) involved mcr. Twenty cases without detectable t(14;18) translocation by PCR were analysed by FISH. Eleven cases were successfully probed, and four of them showed positive translocation signal.

    CONCLUSIONS: The combination of PCR and FISH analysis on paraffin tissue sections for the detection of t(14;18) translocation increases the sensitivity of detection from 60 to 68%. Problems encountered in our FISH analysis on tissue sections impose certain limitations in using this technique for retrospective screening of large number of samples. Therefore, we suggested the application of PCR as the first screening tool on retrospective archival materials, followed by FISH on those PCR-negative cases.

    Matched MeSH terms: Lymphoma, Follicular/pathology
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