Displaying publications 1 - 20 of 66 in total

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  1. 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: In Situ Hybridization, Fluorescence*
  2. 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: In Situ Hybridization, Fluorescence/methods*
  3. Peh SC, Shaminie J, Tai YC, Tan J, Gan SS
    Histopathology, 2004 Nov;45(5):501-10.
    PMID: 15500654
    Follicular lymphoma is frequently associated with t(14;18)(q32;q21) translocation. This study was undertaken to determine the pattern of Bcl-2, CD10 and Bcl-6 expression in relation to t(14;18) translocation in follicular lymphoma from a cohort of a multi-ethnic Asian population.
    Matched MeSH terms: In Situ Hybridization, Fluorescence
  4. Tai YC, Tan JA, Peh SC
    Virchows Arch., 2004 Nov;445(5):506-14.
    PMID: 15365830
    t(11;18)(q21;q21) Translocation and trisomy 3 are the most common chromosomal aberrations reported in low-grade mucosa-associated lymphoid tissue (MALT) lymphoma. The current study aims to investigate the frequency of these chromosomal aberrations in a series of 52 extranodal B-cell lymphomas. The tumours were categorised into three histological grades: grade 1 (low-grade lymphoma of MALT type), grade 2 [diffuse large B-cell lymphoma (DLBCL) with MALT component] and grade 3 (DLBCL without MALT component). Fluorescence in situ hybridisation analyses on paraffin tissue sections were performed using a locus-specific probe for the 18q21 region and a centromeric probe for chromosome 3. The 18q21 rearrangement was detected in 9 of 40 (23%) cases, including 7 of 23 (30%) grade-1 and 2 of 11 (18%) grade-3 tumours. Amplification of the 18q21 region was detected in 10 of 40 (25%) cases, and trisomy 3 was detected in 9 of 34 (26%) cases. Amplification of the 18q21 region may be an important alternative pathogenetic pathway in MALT lymphoma and was found almost exclusively in tumours without 18q21 rearrangement. Our study showed that tumours with 18q21 rearrangement and 18q21 amplification develop along two distinct pathways, and the latter was more likely to transform into high-grade tumours upon acquisition of additional genetic alterations, such as trisomy 3. Trisomy 3 was more frequently found in coexistence with 18q21 abnormalities, suggesting that it was more likely to be a secondary aberration.
    Matched MeSH terms: In Situ Hybridization, Fluorescence
  5. Kim LH, Peh SC, Poppema S
    Hum Pathol, 2006 Jan;37(1):92-100.
    PMID: 16360421
    Deregulation of several genes involved in cell cycle control has been reported in classic Hodgkin lymphoma (cHL). This study aimed to investigate the expression of tumor suppressor proteins (P16(INK4A), retinoblastoma protein, and p53) in cHL in relation to the proliferation and apoptosis of Hodgkin/Reed-Sternberg (H/RS) cells, correlating with the status of Epstein-Barr virus (EBV). A total of 66 cHL cases and 10 nonneoplastic reactive lymphoid tissues were retrieved from the archives. Immunohistochemistry technique was used for the detection of protein expression. Presence of EBV infection was detected by EBV early RNA in situ hybridization. p16(INK4A) gene deletion status was assessed by fluorescence in situ hybridization technique. Expression of P16(INK4A) was observed in 49.2% of the cases, whereas positive retinoblastoma protein and p53 expressions in the H/RS cells were detected in 89.1% and 81.5% of the cases, respectively. Epstein-Barr virus positivity was detected in 53.0% of the cases. Proliferation marker, Ki-67 expression, was observed in 86.7% of the cases. There was no significant correlation between the expression of the various tumor suppressor proteins and Ki-67. Retinoblastoma protein and p53 were also not associated with the presence of EBV. An inverse relationship was observed between the expression of P16(INK4A) and the presence of EBV. There were no significant homozygous or hemizygous deletions of the p16(INK4A) gene. However, an aberrant copy number of chromosome 9 with the loss of one or more p16(INK4A) loci was detected in all cases assessable by fluorescence in situ hybridization. Loss of function of one or more tumor suppressor proteins may be involved in defective cell regulation of H/RS cells. Epstein-Barr virus may have a role in inhibiting P16(INK4A) expression, thus resulting in a perturbed p16(INK4A)-Rb cell cycle checkpoint.
    Matched MeSH terms: In Situ Hybridization, Fluorescence
  6. Salwati Shuib, Sharifah Noor Akmal, Zarina Abdul Latif, Nor Zarina Zainal Abidin, Zubaidah Zakaria
    Medicine & Health, 2006;1(1):45-52.
    MyJurnal
    In this report we demonstrate the role of fluorescence in situ hybridisation (FISH) and conventional cytogenetic methods in clinically and cytogenetically confirmed cases of microdeletion syndromes. A total of nine cases were referred to the Cytopathology and Cytogenetic Unit, Hospital Universiti Kebangsaan Malaysia (HUKM) from 2002 to 2004. They include three Prader-Willi syndrome, three DiGeorge syndrome, one Williams syndrome, one Miller-Dieker syndrome and one Kallmann syndrome. Blood samples from the patients were cultured and harvested following standard procedures. Twenty metaphases were analysed for each of the cases. FISH analysis was carried out for all the cases using commercial probes (Vysis, USA): SNRPN and D15S10 for Prader-Willi syndrome, LIS1 for Miller Dieker syndrome, ELN for Williams syndrome, KAL for Kallmann syndrome, TUPLE 1 and D22S75 for DiGeorge syndrome. Conventional cytogenetic analysis revealed normal karyotypes in all but one case with structural abnormality involving chromosomes 9 and 22. FISH analysis showed microdeletions in all of the nine cases studied. This study has accomplished two important findings ie. while the FISH method is mandatory in ruling out microdeletion syndromes, conventional cytogenetics acts as a screening tool in revealing other chromosomal abnormalities that may be involved with the disease.
    Matched MeSH terms: In Situ Hybridization, Fluorescence
  7. Wong EH, Subramaniam G, Navaratnam P, Sekaran SD
    Indian J Med Microbiol, 2007 Oct;25(4):391-4.
    PMID: 18087092
    Fluorescent in situ hybridization (FISH) was carried out using two different oligonucleotide probes specific for Pseudomonas spp. and Acinetobacter spp. These probes were tested against different organisms and were found to be highly specific. Sensitivity testing showed that the probes were able to detect as low as 10 3 CFU/mL. In addition, FISH was carried out directly on positive blood culture samples and the detection of microorganisms took less than 2 h. We believe that FISH is a rapid method that can be used as a routine laboratory diagnostic technique for the detection of Acinetobacter spp. and Pseudomonas spp. in clinical samples.
    Matched MeSH terms: In Situ Hybridization, Fluorescence/methods*
  8. Chin SF, Hamid NA, Latiff AA, Zakaria Z, Mazlan M, Yusof YA, et al.
    Nutrition, 2008 Jan;24(1):1-10.
    PMID: 17884341
    The free radical theory of aging (FRTA) suggests that free radicals are the leading cause of deteriorating physiologic function during senescence. Free radicals attack cellular structures or molecules such as DNA resulting in various modifications to the DNA structures. Accumulation of unrepaired DNA contributes to a variety of disorders associated with the aging process.
    Matched MeSH terms: In Situ Hybridization, Fluorescence
  9. Phan CL, Megat Baharuddin PJ, Chin LP, Zakaria Z, Yegappan S, Sathar J, et al.
    Cancer Genet. Cytogenet., 2008 Jan 1;180(1):60-4.
    PMID: 18068536
    The Philadelphia (Ph) chromosome, or t(9;22), is the hallmark of chronic myelogenous leukemia (CML). It results in juxtaposition of the 5' part of the BCR gene on chromosome 22 to the 3' part of the ABL1 gene (previously ABL) on chromosome 9. CML is clinically characterized by three distinct phases: chronic, accelerated, and blast phase. Blast crisis is characterized by the rapid expansion of a population of differentiation arrested blast cells (myeloid or lymphoid cells population), with secondary chromosomal abnormalities present. We report a case of myeloid blast crisis of CML resistant to imatinib mesylate and chemotherapy. By use of cytogenetic, fluorescence in situ hybridization, and comparative genomic hybridization methods, we identified a cluster of BCR-ABL amplification on inverted duplication of the Ph chromosome with t(3;21)(q26;q22) and increased genomic levels of the RUNX1 gene (previously AML1). The t(3;21)(q26;q22) is a recurrent chromosomal abnormality in some cases of CML blast phase and in treatment-related myelodysplastic syndrome and acute myeloid leukemia. Amplification or copy number increase of RUNX1 has been reported in childhood acute lymphoblastic leukemia. Our study indicated that the progenitor of CML was BCR-ABL dependent through the amplification of Ph chromosome as a mechanism of resistance to imatinib therapy. The coexistence of BCR-ABL and t(3;21)(q26;q22) with RUNX1 rearrangement might play a pivotal role in the CML blast transformation.
    Matched MeSH terms: In Situ Hybridization, Fluorescence
  10. Palasubramaniam S, Muniandy S, Navaratnam P
    J Microbiol Methods, 2008 Jan;72(1):107-9.
    PMID: 18054098
    Multi-resistant Enterobacteriaceae pose a serious threat of hospital acquired infections and their rapid identification is important for better clinical outcome. This study describes the rapid identification of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae of the sulphydryl variable-type by fluorescent in-situ hybridization. The method which rapidly identifies the target genes within 1 h could be a potentially rapid bacterial diagnostic tool.
    Matched MeSH terms: In Situ Hybridization, Fluorescence/methods*
  11. Mdzin R, Ko C, Abdul Latif Z, Zakaria Z
    Singapore Med J, 2008 Nov;49(11):e336-9.
    PMID: 19037546
    Interstitial deletions of the long arm of chromosome 4 are rare. The deletions may occur at the proximal or the distal portions of the chromosome and different breakpoints may be involved. We report an interstitial deletion of 4q: 46XY der 4 (q28;q35) in a six-year-old boy with dysmorphic features associated with moderate mental retardation. Parental chromosomal analysis showed a balanced paternal translocation.
    Matched MeSH terms: In Situ Hybridization, Fluorescence
  12. Reena Rahayu Md Zin, Sharifah Noor Akmal, Zubaidah Zakaria, Haut, Clarence Ko Ching, Siti Mariam Yusof, Julia Mohd Idris, et al.
    Medicine & Health, 2008;3(1):22-29.
    MyJurnal
    Turner syndrome is one of the most common chromosomal abnormalities affecting newborn females. More than half of patients with Turner syndrome have a 45X karyotype The rest of the patients may have structurally abnormal sex chromosomes or are mosaics with normal or abnormal sex chromosomes. Mosaicism with a second X sex chromosome is not usually of clinical significance. However, Turner syndrome patients having a second Y chromosome or Y chromosomal material are at risk of developing gonadoblastoma later in life. The aim of this study is to compare the results of conventional (karyotyping) and molecular cytogenetics (FISH), and discuss the advantages and limitations in the diagnosis of Turner syndrome. We also aim to compare the degree of mosaicism identified using conventional cytogenetics and FISH techniques. Conventional cytogenetics and FISH analyses were performed on eight peripheral blood samples of patients with Turner syndrome collected between 2004 and 2006. From this study, two out of eight patients with Turner syndrome were found to have the sex determining region on the Y chromosome (SRY) gene by FISH analysis. Our results showed that the rate of detection of mosaic cases in Turner syndrome was also increased to 88% after using the FISH technique. We concluded that FISH is more superior to conventional cytogenetics in the detection of the Y chromosomal material. FISH is also a quick and cost effective method in diagnosing Turner syndrome and assessing the degree of mosaicism.
    Matched MeSH terms: In Situ Hybridization, Fluorescence
  13. Siti-Aishah, M.A., Salwati, S., Idrus, M., Rahimah, R., Salmi, A., Leong, C.F., et al.
    Medicine & Health, 2008;3(1):69-74.
    MyJurnal
    Anaplastic large cell lymphoma (ALCL) is a rare tumour, accounting for approximately 3% of adult non-Hodgkin lymphomas.1 Primary systemic ALCL frequently involves both lymph nodes and extranodal sites. A 44-year-old woman presented with a firm, mobile mass in the left iliac fossa region. Ultrasound findings showed a well defined inhomogenous soft tissue mass, measuring 4x4x2.6cm in the deep subcutaneous region. Histopathological examination revealed that the mass was infiltrated by large lymphoid cells with marked nuclear atypia including kidney-shaped nuclei. These neoplastic cells expressed anaplastic lymphoma kinase (ALK) (both nuclear & cytoplasmic staining), CD30 and EMA but not for T-cell (CD45RO and CD3), and B-cell (CD20 & CD79α) markers. Fluorescence in situ hybridization (FISH) analysis showed a t(2;5)(p23;q35) chromosomal translocation. Subsequently the patient developed shortness of the breath and a thoracic computed tomography (CT) scan showed a mass encasing the right upper lobe bronchus. She also had bilateral axillary lymph nodes, measuring 1 cm in diameter (biopsy was not done). The mediastinum and endobronchial region did not show any abnormalities. She received 6 cycles of CHOP chemotherapy and remained disease free 2 years after diagnosis. ALCL, rarely present as a soft tissue tumour and this disease should be included as a differential diagnosis of any soft tissue mass.
    Matched MeSH terms: In Situ Hybridization, Fluorescence
  14. Masir N, Campbell LJ, Goff LK, Jones M, Marafioti T, Cordell J, et al.
    Br J Haematol, 2009 Mar;144(5):716-25.
    PMID: 19120369 DOI: 10.1111/j.1365-2141.2008.07528.x
    The t(14;18)(q32;q21) chromosomal translocation induces BCL2 protein overexpression in most follicular lymphomas. However the expression of BCL2 is not always homogeneous and may demonstrate a variable degree of heterogeneity. This study analysed BCL2 protein expression pattern in 33 cases of t(14;18)-positive follicular lymphomas using antibodies against two different epitopes (i.e. the widely used antibody BCL2/124 and an alternative antibody E17). 16/33 (49%) cases demonstrated strong BCL2 expression. In 10/33 (30%) cases, BCL2 expression was heterogeneous and in some of these, its loss appeared to be correlated with cell proliferation, as indicated by Ki67 expression. Double immunofluorescence labelling confirmed an inverse BCL2/Ki67 relationship, where in 24/28 (86%) cases cellular expression of BCL2 and Ki67 was mutually exclusive. In addition, seven BCL2 'pseudo-negative' cases were identified in which immunostaining was negative with antibody BCL2/124, but positive with antibody E17. Genomic DNA sequencing of these 'pseudo-negative' cases demonstrated eleven mutations in four cases and nine of these were missense mutations. It can be concluded that in follicular lymphomas, despite carrying the t(14;18) translocations, BCL2 protein expression may be heterogeneous and loss of BCL2 could be related to cell proliferation. Secondly, mutations in translocated BCL2 genes appear to be common and may cause BCL2 pseudo-negative immunostaining.
    Matched MeSH terms: In Situ Hybridization, Fluorescence/methods
  15. Kuan JW, Pathmanathan R, Chang KM, Tan SM
    Leuk. Res., 2009 Nov;33(11):1574-7.
    PMID: 19215983 DOI: 10.1016/j.leukres.2009.01.016
    Granulocytic sarcoma (GS) can occur de novo or in association with intramedullary myeloid disorders. With the advent of sophisticated molecular detection techniques to detect diagnostic genes such as bcr-abl, PML-RARA and CBFB/MYH11 in bone marrow or peripheral blood, many cases of the so called 'primary' GS are questionable. We report a case of primary GS where the tumor mass bcr-abl translocation was demonstrated by fluorescent in situ hybridization in which there was no evidence of chronic myeloid leukemia (CML). This is an important finding as it highlights the possibility that CML may present as a sole extramedullary form, and illustrates potential treatment by tyrosine kinase inhibitor.
    Matched MeSH terms: In Situ Hybridization, Fluorescence
  16. Shuib S, Abdul Latif Z, Abidin NZ, Akmal SN, Zakaria Z
    Malays J Pathol, 2009 Dec;31(2):133-6.
    PMID: 20514857 MyJurnal
    DiGeorge syndrome is associated with microdeletion of chromosome 22q11.2. Most cases occur sporadically although vertical transmission has been documented. We report a rare case of DiGeorge syndrome in an 8-year-old girl. Blood sample of the patient was cultured and harvested following standard procedure. All of the 20 cells analysed showed a karyotype of 45, XX, -22, t (9;22) (p23; q11.2). Cytogenetic investigation done on the patient's mother revealed that she was the carrier for the translocation. Her karyotype was 46, XX, t (9;22) (p23; q11.2). Fluorescence in situ hybridisation (FISH) analysis using TUPLE1 and N25 (Vysis, USA) probes showed deletion of the 22q11.2 region in the patient, confirming the diagnosis of DiGeorge syndrome. FISH analysis showed no deletion of the region in the mother.
    Matched MeSH terms: In Situ Hybridization, Fluorescence
  17. Chia WK, Sharifah NA, Reena RM, Zubaidah Z, Clarence-Ko CH, Rohaizak M, et al.
    Cancer Genet. Cytogenet., 2010 Jan 1;196(1):7-13.
    PMID: 19963130 DOI: 10.1016/j.cancergencyto.2009.08.001
    At the present time, the differentiation between follicular thyroid carcinoma (FTC) and adenoma can be made only postoperatively and is based on the presence of capsular or vascular invasion. The ability to differentiate preoperatively between the malignant and benign forms of follicular thyroid tumors assumes greater importance in any clinical setting. The PAX8-PPARG translocation has been reported to occur in the majority of FTC. In this study, a group of 60 follicular thyroid neoplasms [18 FTC, 1 Hurthle cell carcinoma (HCC), 24 follicular thyroid adenomas (FTA), 5 Hurthle cell adenomas (HCA), and 12 follicular variants of papillary thyroid carcinomas (FV-PTC)] were analyzed to determine the prevalence of the PAX8-PPARG translocation by fluorescence in situ hybridization. The PAX8-PPARG translocation was detected in 2/18 FTC (11.1%). In addition, 2/18 (11.1%) FTC and 1/5 (20%) HCA showed 3p25 aneusomy only. The frequency of the translocation detected in the study was lower compared to the earlier studies conducted in Western countries. This might be attributed to the ethnic background and geographic location. Detection of either the PAX8-PPARG translocation or the 3p25 aneusomy in FTC indicates that these are independent genetic events. It is hereby concluded that 3p25 aneusomy or PAX8-PPARG translocation may play an important role in the molecular pathogenesis of follicular thyroid tumors.
    Matched MeSH terms: In Situ Hybridization, Fluorescence
  18. Masir N, Jones M, Lee AM, Goff LK, Clear AJ, Lister A, et al.
    Histopathology, 2010 Apr;56(5):617-26.
    PMID: 20459572 DOI: 10.1111/j.1365-2559.2010.03524.x
    To investigate the relationship between Bcl-2 protein expression and cell proliferation at single-cell level in B-cell lymphomas using double-labelling techniques.
    Matched MeSH terms: In Situ Hybridization, Fluorescence
  19. Masir N, Campbell LJ, Jones M, Mason DY
    Pathology, 2010 Apr;42(3):212-6.
    PMID: 20350212 DOI: 10.3109/00313021003631296
    The t(14;18)(q32;q21) chromosomal translocation induces BCL2 protein expression in most follicular lymphomas. However, a small number of cases lack BCL2 expression despite carrying the t(14;18)(q32;q21) translocation. This study aims to explore the mechanism accounting for the lack of BCL2 protein expression when the t(14;18) translocation is present.
    Matched MeSH terms: In Situ Hybridization, Fluorescence
  20. Shaariyah MM, Mazita A, Masaany M, Razif MY, Isa MR, Asma A
    Chin J Cancer, 2010 Jun;29(6):631-3.
    PMID: 20507738
    Synovial sarcoma is a rare soft tissue sarcoma of the head and neck region involving the parapharyngeal space. The diagnosis of synovial sarcoma can be very challenging to the pathologists. We present a rare case of parapharyngeal synovial sarcoma in a young female patient who had a two-month history of left cervical intumescent mass at level II. The fine needle aspiration cytology of the mass was proved inconclusive. Transcervical excision of the mass was performed and the first case of parapharyngeal sarcoma was identified in our center by fluorescence in situ hybridization (FISH) technique. Repeat imaging revealed residual tumor. The patient successfully underwent a second excision of the residual tumor and received adjuvant radiotherapy.
    Matched MeSH terms: In Situ Hybridization, Fluorescence
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