Displaying publications 21 - 40 of 44 in total

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  1. Expression of p53, bcl-2 and Ki-67 in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix
    Looi ML, Dali AZ, Ali SA, Ngah WZ, Yusof YA
    Anal. Quant. Cytol. Histol., 2008 Apr;30(2):63-70.
    PMID: 18561741
    To assess the expression of p53, bcl-2 and Ki-67 in the progression of cervical neoplasia.
  2. Fulltext ER, p53 and MIB-1 are significantly associated with malignant phyllodes tumor
    Munawer NH, Md Zin R, Md Ali SA, Muhammad R, Ali J, Das S
    Biomed J, 2012 Nov-Dec;35(6):486-92.
    PMID: 23442362 DOI: 10.4103/2319-4170.104414
    Fibroadenomas (FA) are common while phyllodes tumors (PT) are rare and both tumors are composed of epithelial and stromal components. We evaluated the expression status of ER, Bc12, p53, and MIB-1 protein in these tumors.
  3. Hallmarks of HIV-1 pathogenesis are modulated by Nef's Secretion Modification Region
    Konadu KA, Anderson JS, Huang MB, Ali SA, Powell MD, Villinger F, et al.
    J AIDS Clin Res, 2015 Jul;6(7).
    PMID: 26523240
    CD4(+) T cell depletion and immune activation are hallmarks of HIV infection. Despite extensive studies, the mechanisms underlying immune modulation remain elusive. HIV-1 Nef protein is secreted in exosomes from infected cells and is abundant in the plasma of HIV+ individuals. Exosomal Nef (exNef) was also shown to induce apoptosis in bystander CD4(+) T cells. We hypothesized that exNef contributes to HIV pathogenesis. A HIV-1 NL4-3 virus containing alanine substitutions in the secretion modification region (SMR; amino acids 66 to 70; HIVNefsmr5a) was developed. Nef protein containing this modified SMR was shown to be deficient in exNef secretion in nef-transfected cells. Using both HIV-1 NL4-3 wild type (HIVwt) and HIVNefsmr5a, correlates of pathogenesis were evaluated in cell-lines, human peripheral blood mononuclear cells, and humanized NOD-RAG1(-/-) IL2r(-/-) double mutant (NRG) mice. Disruption of the SMR did not affect viral replication or exNef secretion from infected cell cultures as compared with nef-transfected cells. However, T cell apoptosis was reduced in HIVNefsmr5a infected cell cultures and CD4(+) T cell depletion was reduced in the spleen and peripheral blood of similarly infected NRG mice. Inflammatory cytokine release was also decreased in the sera of HIVNefsmr5a infected mice relative to HIVwt infected controls. These findings demonstrate the importance of Nef and the SMR motif in HIV pathogenesis and suggest a potential role for exNef in HIV-driven immune modulation.
  4. Fulltext Engineering and Validation of a Vector for Concomitant Expression of Rare Transfer RNA (tRNA) and HIV-1 nef Genes in Escherichia coli
    Mualif SA, Teow SY, Omar TC, Chew YW, Yusoff NM, Ali SA
    PLoS One, 2015;10(7):e0130446.
    PMID: 26147991 DOI: 10.1371/journal.pone.0130446
    Relative ease in handling and manipulation of Escherichia coli strains make them primary candidate to express proteins heterologously. Overexpression of heterologous genes that contain codons infrequently used by E. coli is related with difficulties such as mRNA instability, early termination of transcription and/or translation, deletions and/or misincorporation, and cell growth inhibition. These codon bias -associated problems are addressed by co-expressing ColE1-compatible, rare tRNA expressing helper plasmids. However, this approach has inadequacies, which we have addressed by engineering an expression vector that concomitantly expresses the heterologous protein of interest, and rare tRNA genes in E. coli. The expression vector contains three (argU, ileY, leuW) rare tRNA genes and a useful multiple cloning site for easy in-frame cloning. To maintain the overall size of the parental plasmid vector, the rare tRNA genes replaced the non-essential DNA segments in the vector. The cloned gene is expressed under the control of T7 promoter and resulting recombinant protein has a C-terminal 6His tag for IMAC-mediated purification. We have evaluated the usefulness of this expression vector by expressing three HIV-1 genes namely HIV-1 p27 (nef), HIV-1 p24 (ca), and HIV-1 vif in NiCo21(DE3) E.coli and demonstrated the advantages of using expression vector that concomitantly expresses rare tRNA and heterologous genes.
  5. Antibacterial Action of Curcumin against Staphylococcus aureus: A Brief Review
    Teow SY, Liew K, Ali SA, Khoo AS, Peh SC
    J Trop Med, 2016;2016:2853045.
    PMID: 27956904
    Curcumin, the major constituent of Curcuma longa L. (Zingiberaceae family) or turmeric, commonly used for cooking in Asian cuisine, is known to possess a broad range of pharmacological properties at relatively nontoxic doses. Curcumin is found to be effective against Staphylococcus aureus (S. aureus). As demonstrated by in vitro experiment, curcumin exerts even more potent effects when used in combination with various other antibacterial agents. Hence, curcumin which is a natural product derived from plant is believed to have profound medicinal benefits and could be potentially developed into a naturally derived antibiotic in the future. However, there are several noteworthy challenges in the development of curcumin as a medicine. S. aureus infections, particularly those caused by the multidrug-resistant strains, have emerged as a global health issue and urgent action is needed. This review focuses on the antibacterial activities of curcumin against both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). We also attempt to highlight the potential challenges in the effort of developing curcumin into a therapeutic antibacterial agent.
  6. Oxidative damage and antioxidant status in patients with cervical intraepithelial neoplasia and carcinoma of the cervix
    Looi ML, Mohd Dali AZ, Md Ali SA, Wan Ngah WZ, Mohd Yusof YA
    Eur J Cancer Prev, 2008 Nov;17(6):555-60.
    PMID: 18941377 DOI: 10.1097/CEJ.0b013e328305a10b
    Free radicals that induced lipid peroxidation and DNA damage have been implicated in many diseases including cancer. Cellular antioxidant defense plays an important role in neoplastic disease to counteract oxidative damage. This study aims to investigate the status of oxidative damage by measuring plasma malondialdehyde (MDA) level and urinary 8-hydroxydeoxyguanosine (8-OHdG), and the level of antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase in patients with cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC) of the cervix. Urinary 8-OHdG was measured by an enzyme-linked immunosorbent assay kit. MDA and antioxidant enzyme activities were determined by high-performance liquid chromatography and spectrophotometry, respectively. Eighty patients with CIN and SCC of the cervix were recruited and compared with normal controls. Urinary 8-OHdG/creatinine ratio did not show any significant changes in any disease status studied as compared with controls (P=0.803). Plasma MDA was found to be increased in CIN and SCC patients when compared with controls (P=0.002). Glutathione peroxidase activity was increased (P=0.0001) whereas superoxide dismutase and catalase activity was decreased (P=0.019 and 0.0001, respectively) in both CIN and SCC patients when compared with controls. Urinary 8-OHdG may not be a good marker for enhanced oxidative stress in cervical cancer. Oxidative damage as demonstrated by the level of MDA is markedly increased in CIN and SCC patients with changes of enzymatic antioxidants observed.
  7. Exploring breast carcinogenesis through integrative genomics and epigenomics analyses
    Minning C, Mokhtar NM, Abdullah N, Muhammad R, Emran NA, Ali SA, et al.
    Int J Oncol, 2014 Nov;45(5):1959-68.
    PMID: 25175708 DOI: 10.3892/ijo.2014.2625
    There have been many DNA methylation studies on breast cancer which showed various methylation patterns involving tumour suppressor genes and oncogenes but only a few of those studies link the methylation data with gene expression. More data are required especially from the Asian region and to analyse how the epigenome data correlate with the transcriptome. DNA methylation profiling was carried out on 76 fresh frozen primary breast tumour tissues and 25 adjacent non-cancerous breast tissues using the Illumina Infinium(®) HumanMethylation27 BeadChip. Validation of methylation results was performed on 7 genes using either MS-MLPA or MS-qPCR. Gene expression profiling was done on 15 breast tumours and 5 adjacent non-cancerous breast tissues using the Affymetrix GeneChip(®) Human Gene 1.0 ST array. The overlapping genes between DNA methylation and gene expression datasets were further mapped to the KEGG database to identify the molecular pathways that linked these genes together. Supervised hierarchical cluster analysis revealed 1,389 hypermethylated CpG sites and 22 hypomethylated CpG sites in cancer compared to the normal samples. Gene expression microarray analysis using a fold-change of at least 1.5 and a false discovery rate (FDR) at p>0.05 identified 404 upregulated and 463 downregulated genes in cancer samples. Integration of both datasets identified 51 genes with hypermethylation with low expression (negative association) and 13 genes with hypermethylation with high expression (positive association). Most of the overlapping genes belong to the focal adhesion and extracellular matrix-receptor interaction that play important roles in breast carcinogenesis. The present study displayed the value of using multiple datasets in the same set of tissues and how the integrative analysis can create a list of well-focused genes as well as to show the correlation between epigenetic changes and gene expression. These gene signatures can help us understand the epigenetic regulation of gene expression and could be potential targets for therapeutic intervention in the future.
  8. Fulltext Production and purification of polymerization-competent HIV-1 capsid protein p24 (CA) in NiCo21(DE3) Escherichia coli
    Teow SY, Mualif SA, Omar TC, Wei CY, Yusoff NM, Ali SA
    BMC Biotechnol, 2013;13:107.
    PMID: 24304876 DOI: 10.1186/1472-6750-13-107
    HIV genome is packaged and organized in a conical capsid, which is made up of ~1,500 copies of the viral capsid protein p24 (CA). Being a primary structural component and due to its critical roles in both late and early stages of the HIV replication cycle, CA has attracted increased interest as a drug discovery target in recent years. Drug discovery studies require large amounts of highly pure and biologically active protein. It is therefore desirable to establish a simple and reproducible process for efficient production of HIV-1 CA.
  9. Fulltext Epidemiology of latent tuberculosis infection among patients with and without diabetes mellitus
    Swarna Nantha Y, Puri A, Mohamad Ali SZ, Suppiah P, Che Ali SA, Ramasamy B, et al.
    Fam Pract, 2017 09 01;34(5):532-538.
    PMID: 28369346 DOI: 10.1093/fampra/cmx017
    Background: Individuals with type 2 diabetes mellitus (DM) are at a greater risk of tuberculosis (TB) reactivation. There is a paucity of information about the risk factors associated with latent tuberculosis infection (LTBI) in patients with diabetes.

    Objective: We conducted an observational study to compare the prevalence and risk factors associated with LTBI factors in Malaysian adults with and without DM.

    Methods: Four hundred and four patients with DM and 359 patients with non-DM at a regional primary care clinic were recruited as participants in this case-control study. The tuberculin sensitivity test (TST) was performed. The presence of LTBI was defined by a TST value of 10 mm in DM patients and 10 mm in the non-DM group. A logistic regression model was used to identify variables associated with LTBI.

    Results: There was no statistical significant difference in the prevalence rates seen between the DM and non-DM group of the study. LTBI prevalence among patients with DM was 28.5%. The proportion of patients in the non-DM group with LTBI was 29.2%. When a critical cut-off of 8 mm was used, the adjusted odds ratio of LTBI in DM patients was 1.88 (95% confidence interval: 1.22-2.82). Smoking was an independent risk factor for LTBI regardless of DM status. HbA1c levels or anthropometric measurements were not associated with LTBI in diabetic patients.

    Conclusions: There is no significant risk of contracting LTBI in DM patients using the standard 10-mm TST cut-off. Nonetheless, using lower cut-offs in a DM population appear valid. Smoking is an important predictor of LTBI.
  10. Aerosolised Mesenchymal Stem Cells Expressing Angiopoietin-1 Enhances Airway Repair
    Halim NSS, Ch'ng ES, Kardia E, Ali SA, Radzi R, Yahaya BH
    Stem Cell Rev Rep, 2019 02;15(1):112-125.
    PMID: 30178289 DOI: 10.1007/s12015-018-9844-7
    BACKGROUND: The aim of this study was to investigate the effects of MSCs and MSC-expressing ANGPT1 (MSC-pANGPT1) treatment via aerosolisation in alleviating the asthma-related airway inflammation in the rabbit model.

    METHODS: Rabbits were sensitised and challenged with both intraperitoneal injection and inhalation of ovalbumin (Ova). MSCs and MSC-pANGPT1 cells were aerosolised into rabbit lungs using the MicroSprayer® Aerosolizer Model IA-1B 48 h after injury. The post mortem was performed 3 days following cell delivery. Histopathological assessments of the lung tissues and inflammatory response were quantitatively scored following treatments.

    RESULT(S): Administration of aerosolised MSCs and MSC-pANGPT1 were significantly reduced inflammation of the airways (p 

  11. Fulltext Granulomatous hypophysitis: a case of severe headache
    Wan Muhamad Hatta SF, Hamdan MF, Md Ali SA, Abdul Ghani R
    BMJ Case Rep, 2016 Sep 09;2016.
    PMID: 27613264 DOI: 10.1136/bcr-2016-216395
    Idiopathic granulomatous hypophysitis (GH) is an uncommon inflammatory disease of the pituitary with impairment of pituitary gland function due to infiltration by lymphocytes, plasma cells and macrophages. We report the case of a 39-year-old woman who presented with worsening of headaches for 1 month and blurring of vision over 5 days. An MRI revealed a homogeneous supra-sellar mass evoking a pituitary tumour with bulky pituitary stalk extending into the left and right cavernous sinuses. Hormonal investigations showed anterior pituitary hormone deficiencies; meanwhile histopathological examination revealed an aspect of hypophysitis. Clinical and radiological remission occurred immediately postglucocorticoid therapy with the addition of a steroid-sparing agent later in view of recurrence of symptoms on glucocorticoid dose reduction. GH has important diagnostic and therapeutic implications, as clinical and radiological features ameliorate via medical treatment. With further understanding and recognition of the disease, we hope to highlight a case of GH, in which signs and symptoms improved after initiation of corticosteroids.
  12. Ezrin is Significantly Overexpressed in Luminal A, Luminal B, and HER2 Subtype Breast Cancer
    Jais MH, Md Zin RR, Muhd Hanapi NA, Md Ali SA
    Appl Immunohistochem Mol Morphol, 2017 01;25(1):44-48.
    PMID: 26469327
    Ezrin, a membrane-linking protein, has been shown to play an important role in the carcinogenesis of infiltrating breast ductal carcinoma and its strong expression has been used to predict poor prognosis in patients with breast carcinoma. In this study, we compared ezrin protein distribution pattern in benign breast disease and breast cancer molecular subtypes and evaluated their association with clinicopathologic variables. A total of 376 breast cases (142 benign and 234 malignant cases) were studied. Immunohistochemical analysis for ezrin was performed and its expression was observed in terms of its distribution, intensity, and proportion of cells reactive for ezrin. Ezrin was expressed in all benign cases and 91.7% of malignant cases. Apical staining was positively associated with benign breast disease, whereas membranous and cytoplasmic staining were more frequently observed in malignant cases, specifically of hormone receptor-positive subtypes (luminal A and luminal B). Ezrin was significantly overexpressed in luminal A, luminal B, and HER2 subtypes. Reduced ezrin expression was significantly associated with triple-negative breast cancer molecular subtype. No significant association was demonstrated between ezrin expression and Her2 gene amplification, tumor grading, or staging.
  13. Fulltext A case of acute motor sensory axonal neuropathy variant of Guillain Barre syndrome and anaphylaxis reaction as a complication from hyaluronic acid breast enhancement from an unlicensed beautician
    Ng YJ, Ling A, Nam LJ, Tylors PS, Bin Maliki AH, Wan Ali SA
    J Surg Case Rep, 2023 May;2023(5):rjad254.
    PMID: 37215624 DOI: 10.1093/jscr/rjad254
    Guillain Barre syndrome (GBS) as a complication of hyaluronic acid (HA) exposure is an extremely rare occurrence. We report a case of GBS, acute motor sensory axonal neuropathy (AMSAN) variant, after a HA breast enhancement procedure. A 41-year-old lady underwent a HA breast enhancement procedure from an unlicensed beautician and developed anaphylaxis followed by bilateral breast abscess and neurological deficits involving both motor and sensory components. The AMSAN variant of GBS was diagnosed from the cytoalbuminologic dissociation and nerve conduction study. Her GBS and breast abscess were managed with plasmapheresis and bilateral mastectomy. In this case, GBS was highly suspected to be caused by HA with possible impurities. To the author's knowledge, the association between HA and GBS has not been reported or known, and further studies are required to establish this association. To prevent mortality and morbidity, breast enhancement procedures should be performed by trained professionals with properly vetted products.
  14. Fulltext Post-Attentive Integration and Topographic Map Distribution During Audiovisual Processing in Dyslexia: A P300 Event-Related Component Analysis
    Ali SA, Begum T, Reza MF, Fadzil NA, Mustafar F
    Malays J Med Sci, 2020 Jul;27(4):130-138.
    PMID: 32863752 DOI: 10.21315/mjms2020.27.4.12
    Background: Research on audiovisual post-attentive integration has been carried out using a variety of experimental paradigms and experimental groups but not yet studied in dyslexia. We investigated post-attentive integration and topographic voltage distribution in children with dyslexia by analysing the P300 event-related potential (ERP) component.

    Methods: We used a 128-child ERP net for the ERP experiment. Two types of stimuli were presented as either congruent or incongruent stimuli. Congruent stimuli included a matching auditory sound with an animal image, whereas incongruent stimuli included unmatched animal sounds. A total of 24 age-matched children were recruited in the control (n = 12) and dyslexia (n = 12) groups. Children pressed button '1' or '2' when presented with congruent or incongruent stimuli, respectively. The P300 amplitudes and latencies with topographic voltage distribution were analysed for both groups.

    Results: The dyslexia group evoked significantly higher P300 amplitudes at the T4 area than the control group. No significant differences were found in cases of P300 latency. Moreover, the dyslexia group demonstrated a higher intensity of P300 voltage distribution in the right parietal and left occipital areas than the control group.

    Conclusion: Post-attentive integration for children with dyslexia is higher and that this integration process implicated the parietal and occipital areas.

  15. Pilot study of the sensitivity and specificity of the DNA integrity assay for stool-based detection of colorectal cancer in Malaysian patients
    Yehya AH, Yusoff NM, Khalid IA, Mahsin H, Razali RA, Azlina F, et al.
    Asian Pac J Cancer Prev, 2012;13(5):1869-72.
    PMID: 22901138
    BACKGROUND: To assess the diagnostic potential of tumor-associated high molecular weight DNA in stool samples of 32 colorectal cancer (CRC) patients compared to 32 healthy Malaysian volunteers by means of polymerase chain reaction (PCR).

    METHODS: Stool DNA was isolated and tumor-associated high molecular weight DNA (1.476 kb fragment including exons 6-9 of the p53 gene) was amplified using PCR and visualized on ethidium bromide-stained agarose gels.

    RESULTS: Out of 32 CRC patients, 18 were positive for the presence of high molecular weight DNA as compared to none of the healthy individuals, resulting in an overall sensitivity of 56.3% with 100% specificity. Out of 32 patients, 23 had tumor on the left side and 9 on the right side, 16 and 2 being respectively positive. This showed that high molecular weight DNA was significantly (p=0.022) more detectable in patients with left side tumor (69.6% vs 22.2%). Out of 32 patients, 22 had tumors larger than 1.0 cm, 18 of these (81.8%) being positive for long DNA as compared to not a single patient with tumor size smaller than 1.0 cm (p<0.001).

    CONCLUSION: We detected CRC-related high molecular weight p53 DNA in stool samples of CRC patients with an overall sensitivity of 56.3% with 100% specificity, with a strong tumor size dependence.

  16. Construction and evaluation of a O139 Vibrio cholerae vaccine candidate based on a hemA gene mutation
    Ravichandran M, Ali SA, Rashid NH, Kurunathan S, Yean CY, Ting LC, et al.
    Vaccine, 2006 May 1;24(18):3750-61.
    PMID: 16102875
    In this paper, we describe the development of VCUSM2, a live metabolic auxotroph of Vibrio cholerae O139. Auxotrophy was achieved by mutating a house keeping gene, hemA, that encodes for glutamyl-tRNA reductase, an important enzyme in the C5 pathway for delta-aminolevulenic acid (ALA) biosynthesis, which renders this strain dependent on exogenous ALA for survival. Experiments using the infant mouse and adult rabbit models show that VCUSM2 is a good colonizer of the small intestine and elicits greater than a four-fold rise in vibriocidal antibodies in vaccinated rabbits. Rabbits vaccinated with VCUSM2 were fully protected against subsequent challenge with 1 x 10(11) CFU of the virulent wild type (WT) strain. Experiments using ligated ileal loops of rabbits show that VCUSM2 is 2.5-fold less toxic at the dose of 1 x 10(6) CFU compared to the WT strain. Shedding of VCUSM2 in rabbits were found to occur for no longer than 4 days and its maximum survival rate in environmental waters is 8 days compared to the greater than 20 days for the WT strain. VCUSM2 is thus a potential vaccine candidate against infection by V. cholerae O139.
  17. Low-cost novel clay earthenware as separator in microbial electrochemical technology for power output improvement
    Daud SM, Daud WRW, Bakar MHA, Kim BH, Somalu MR, Muchtar A, et al.
    Bioprocess Biosyst Eng, 2020 Aug;43(8):1369-1379.
    PMID: 32193754 DOI: 10.1007/s00449-020-02331-7
    A conventional reactor in microbial electrochemical technology (MET) consists of anode and cathode compartments divided by a separator, which is usually a proton exchange membrane (PEM), such as Nafion 117. In this study, a novel porous clay earthenware (NCE) was fabricated as the separator to replace the highly cost PEM. The fabrication of NCEs is with raw clay powder and starch powder that acts as a pore-forming agent at different starch powder contents (10 vol%, 20 vol%, and 30 vol%), ball-milled before hydraulically pressed to form green ceramic pellets and sintered up to 1200 °C. The highest power density of 2250 ± 21 mW/m2 (6.0 A/m2), the internal resistance of 75 ± 24 Ω and coulombic efficiency (CE) of 44 ± 21% were produced for MFC-NCE from 30 vol% starch powder content under batch mode operation. The MFC-PEM combination produced the lowest power density, CE and the highest internal resistance up to 1350 ± 17 mW/m2 (3.0 A/m2), 23 ± 15% and 326 ± 13 Ω, respectively.
  18. Plasma proteome analysis of cervical intraepithelial neoplasia and cervical squamous cell carcinoma
    Looi ML, Karsani SA, Rahman MA, Dali AZ, Ali SA, Ngah WZ, et al.
    J Biosci, 2009 Dec;34(6):917-25.
    PMID: 20093745
    Although cervical cancer is preventable with early detection, it remains the second most common malignancy among women. An understanding of how proteins change in their expression during a particular diseased state such as cervical cancer will contribute to an understanding of how the disease develops and progresses. Potentially, it may also lead to the ability to predict the occurrence of the disease. With this in mind, we aimed to identify differentially expressed proteins in the plasma of cervical cancer patients. Plasma from control, cervical intraepithelial neoplasia (CIN) grade 3 and squamous cell carcinoma (SCC) stage IV subjects was resolved by two-dimensional gel electrophoresis and the resulting proteome profiles compared. Differentially expressed protein spots were then identified by mass spectrometry. Eighteen proteins were found to be differentially expressed in the plasma of CIN 3 and SCC stage IV samples when compared with that of controls. Competitive ELISA further validated the expression of cytokeratin 19 and tetranectin. Functional analyses of these differentially expressed proteins will provide further insight into their potential role(s) in cervical cancer-specific monitoring and therapeutics.
  19. Fulltext Estrogen receptor-negative breast ductal carcinoma: clinicopathological features and MIB-1 (Ki-67) proliferative index association
    Mdpaiman N, Md Ali SA, Mdzin R, Meor Kamal MZ, Md Amin WA, Nallusamy M, et al.
    PLoS One, 2014;9(2):e89172.
    PMID: 24586570 DOI: 10.1371/journal.pone.0089172
    Breast cancer estrogen receptor (ER) status is one of the strong additional factors in predicting response of patients towards hormonal treatment. The main aim of this study was to assess the morphological characteristics and proliferative activity using MIB-1(Ki-67) of estrogen receptor negative invasive breast ductal carcinoma (NOS type) as well as to correlate these features with clinicopathological data. We also aim to study the expression of c-erbB2 in ER negative breast tumors. High proliferative rate (MIB-1 above 20%) was observed in 63 (63.6%) of 99 ER negative tumors and that these tumors were associated with high expression of c-erbB2 (57.6%). We observed that MIB-1 is a reliable independent prognostic indicator for ER negative infiltrating ductal carcinoma in this study.
  20. 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.

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