Displaying publications 21 - 40 of 54 in total

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  1. Cheah PL, Looi LM, Lee GE, Teoh KH, Mun KS, Nazarina AR
    Diagn Pathol, 2011;6:56.
    PMID: 21699710 DOI: 10.1186/1746-1596-6-56
    Endocervicosis in the urinary bladder is a rare benign condition. We present a case in a 37-year-old woman with classical clinical and pathological features of endocervicosis. The unusual observation of endocervical-like mucinous epithelium in continuity with the urothelium in addition to fully developed endocervicosis prompted immunohistochemical profiling of the case using antibodies to cytokeratins (AE1/AE3, CK19, CK7, CK5/6, CK20), HBME-1, estrogen receptor (ER) and progesterone receptor (PR) to assess the relationship of the surface mucinous and endocervicosis glandular epithelia. The surface mucinous epithelium, urothelium and endocervicosis glands were immunopositive for AE1/AE3, CK7 and CK19 while CK20 was only expressed by few urothelial umbrella cells. The surface mucinous epithelium was CK5/6 and HBME-1 immunonegative but showed presence of ER and PR. This was in contrast to the urothelium's expression of CK5/6 but not ER and PR. In comparison, endocervicosis glands expressed HBME-1, unlike the surface mucinous epithelium. The endocervicosis epithelium also demonstrated the expected presence of ER and PR and CK5/6 immunonegativity. The slightly differing immunohistochemical phenotypes of the surface mucinous and morphologically similar endocervicosis glandular epithelium is interesting and requires further clarification to its actual nature. The patient has remained well and without evidence of disease 18-months following transurethral resection of the lesion.
  2. Cheah PL, Li J, Looi LM, Koh CC, Lau TP, Chang SW, et al.
    Malays J Pathol, 2019 Aug;41(2):91-100.
    PMID: 31427545
    Since 2014, the National Comprehensive Cancer Network (NCCN) has recommended that colorectal carcinoma (CRC) be universally tested for high microsatellite instability (MSI-H) which is present in 15% of such cancers. Fidelity of resultant microsatellites during DNA replication is contingent upon an intact mismatch repair (MMR) system and lack of fidelity can result in tumourigenesis. Prior to commencing routine screening for MSI-H, we assessed two commonly used methods, immunohistochemical (IHC) determination of loss of MMR gene products viz MLH1, MSH2, MSH6 and PMS2 against PCR amplification and subsequent fragment analysis of microsatellite markers, BAT25, BAT26, D2S123, D5S346 and D17S250 (Bethesda markers) in 73 unselected primary CRC. 15.1% (11/73) were categorized as MSI-H while deficient MMR (dMMR) was detected in 16.4% (12/73). Of the dMMR, 66.7% (8/12) were classified MSI-H, while 33.3% (4/12) were microsatellite stable/low microsatellite instability (MSS/MSI-L). Of the proficient MMR (pMMR), 95.1% (58/61) were MSS/MSI-L and 4.9% (3/61) were MSI-H. The κ value of 0.639 (standard error =0.125; p = 0.000) indicated substantial agreement between detection of loss of DNA mismatch repair using immunohistochemistry and the detection of downstream microsatellite instability using PCR. After consideration of advantages and shortcomings of both methods, it is our opinion that the choice of preferred technique for MSI analysis would depend on the type of laboratory carrying out the testing.
  3. Jayapalan RR, Bahuri NFA, Mun KS, Narayanan V
    SAGE Open Med Case Rep, 2019;7:2050313X19828539.
    PMID: 30783531 DOI: 10.1177/2050313X19828539
    Perivascular epithelioid cell tumour is a rare mesenchymal tumour with distinct immunohistochemical profile. While it is known to occur in various anatomical sites, the central nervous system had always been a protected site for primary or secondary perivascular epithelioid cell tumours. We describe a 61-year-old lady who presented with symptoms of raised intracranial pressure, 3 months after the resection of duodenal and thoracic tumours which were histologically consistent with perivascular epithelioid cell tumour. She was investigated and then subsequently subjected to resection of two metastatic intracranial lesions. The radiological, intraoperative as well as histopathological findings of the metastatic lesions are discussed. Metastatic perivascular epithelioid cell tumour of the brain is extremely rare. However, patients who are stratified as high risk for recurrence or metastases should undergo an early magnetic resonance imaging/computed tomography of the brain in addition to a whole-body positron emission tomography scan, to allow for early detection and management of these tumours.
  4. Ho CC, Mun KS, Naidu R
    Malays J Pathol, 2013 Jun;35(1):33-43.
    PMID: 23817393 MyJurnal
    Breast cancer is the most common malignancy in women worldwide. The incidence of breast cancer in Malaysia is lower compared to international statistics, with peak occurrence in the age group between 50 to 59 years of age and mortality rates of 18.6%. Despite current diagnostic and prognostic methods, the outcome for individual subjects remain poor. This is in part due to breast cancers' wide genetic heterogeneity. Various platforms for genetics studies are now employed to determine the identity of these genetic abnormalities, including microarray methods like high density single-nucleotide-polymorphism (SNP) oligonucleotide arrays which combine the power of chromosomal comparative genomic hybridization (cCGH) and loss of heterozygosity (LOH) in the offering of higher-resolution mappings. These platforms and their applications in highlighting the genomic alteration frameworks manifested in breast carcinoma will be discussed.
  5. Subramaniam B, Arshad NM, Malagobadan S, Misran M, Nyamathulla S, Mun KS, et al.
    Pharmaceutics, 2021 Mar 24;13(4).
    PMID: 33804975 DOI: 10.3390/pharmaceutics13040439
    1'-acetoxychavicol acetate (ACA) extracted from the rhizomes of Alpinia conchigera Griff (Zingiberaceae) has been shown to deregulate the NF-ĸB signaling pathway and induce apoptosis-mediated cell death in many cancer types. However, ACA is a hydrophobic ester, with poor solubility in an aqueous medium, limited bioavailability, and nonspecific targeting in vivo. To address these problems, ACA was encapsulated in a nanostructured lipid carrier (NLC) anchored with plerixafor octahydrochloride (AMD3100) to promote targeted delivery towards C-X-C chemokine receptor type 4 (CXCR4)-expressing prostate cancer cells. The NLC was prepared using the melt and high sheer homogenization method, and it exhibited ideal physico-chemical properties, successful encapsulation and modification, and sustained rate of drug release. Furthermore, it demonstrated time-based and improved cellular uptake, and improved cytotoxic and anti-metastatic properties on PC-3 cells in vitro. Additionally, the in vivo animal tumor model revealed significant anti-tumor efficacy and reduction in pro-tumorigenic markers in comparison to the placebo, without affecting the weight and physiological states of the nude mice. Overall, ACA-loaded NLC with AMD3100 surface modification was successfully prepared with evidence of substantial anti-cancer efficacy. These results suggest the potential use of AMD3100-modified NLCs as a targeting carrier for cytotoxic drugs towards CXCR4-expressing cancer cells.
  6. Abdalla YOA, Nyamathulla S, Shamsuddin N, Arshad NM, Mun KS, Awang K, et al.
    Toxicol Appl Pharmacol, 2018 10 01;356:204-213.
    PMID: 30138658 DOI: 10.1016/j.taap.2018.08.014
    1'-S-1'-acetoxychavicol acetate (ACA) has been previously reported to reduce tumor volume in nude mice, at an effective dose of 1.56 mg/kg body weight. However, the detailed toxicological profile for ACA has not yet been performed. Herein, we investigated the toxicity of intravenous administration of ACA in male and female Sprague-Dawley rats, both acutely (with single doses of 2.00, 4.00 and 6.66 mg/kg body weight, for 14 days), and sub-acutely (with weekly injections of 0.66, 1.33, and 2.22 mg/kg, for 28 days). In both toxicity studies, treatment with ACA did not affect behavior, food/water intake or body weight, nor did it induce any changes in clinically relevant hematological and biochemical parameters or mortality, suggesting that the LD50 of ACA was higher than 6.66 mg/kg body weight, regardless of sex. Sub-acutely, there was however, mild focal inflammation of kidneys and lobular hepatitis, but these were not associated with significant functional adverse effects. Therefore, the no-observed-adverse-effect level (NOAEL) for intravenous administration of ACA in the present 28-day sub-acute study was 2.22 mg/kg body weight, in both male and female rats. These findings provide useful information regarding the safety of ACA use in a healthy, non-tumor-bearing rat model.
  7. Subramaniam M, Arshad NM, Mun KS, Malagobadan S, Awang K, Nagoor NH
    Biomolecules, 2019 10 18;9(10).
    PMID: 31635311 DOI: 10.3390/biom9100626
    Cancer development and progression are extremely complex due to the alteration of various genes and pathways. In most cases, multiple agents are required to control cancer progression. The purpose of this study is to investigate, using a mouse model, the synergistic interactions of anti-cancer agents, 1'-S-1'-acetoxychavicol acetate (ACA), Mycobacterium indicus pranii (MIP), and cisplatin (CDDP) in double and triple combinations to treat chemo-sensitize and immune-sensitize breast cancer. Changes in tumor volume and body weight were monitored. Organs were harvested and stained using hematoxylin-eosin for histopathological assessment. Milliplex enzyme-linked immunosorbent assay (ELISA) was performed to determine cytokine levels, while immunohistochemistry (IHC) was conducted on tumor biopsies to verify systemic drug effects. In vivo mouse models showed tumor regression with maintenance of regular body weight for all the different treatment regimens. IHC results provided conclusive evidence indicating that combination regimens were able to down-regulate nuclear factor kappa-B activation and reduce the expression of its regulated pro-inflammatory proteins. Reduction of pro-inflammatory cytokines (e.g., IL-6, TNF-α, and IFN-ɣ) levels were observed when using the triple combination, which indicated that the synergistic drug combination was able to significantly control cancer progression. In conclusion, ACA, MIP, and CDDP together serve as promising candidates for further development and for subsequent clinical trials against estrogen-sensitive breast cancer.
  8. Teoh KH, Looi LM, Sabaratnam S, Cheah PL, Nazarina AR, Mun KS
    Malays J Pathol, 2011 Jun;33(1):35-42.
    PMID: 21874750 MyJurnal
    Predictive biomarkers such as oestrogen (ER) and progesterone (PR) receptors and c-erbB-2 oncoprotein have become a staple in breast cancer reports in the country as they increasingly play an important role in the treatment and prognosis of women with breast cancers. This study reviews the practice of histopathology reporting of these biomarkers in a Malaysian tertiary hospital setting. Retrospective data on demographic, pathological and biomarker profiles of patients with invasive ductal carcinoma who had undergone mastectomy or lumpectomy with axillary node clearance from 2005 to 2006 were retrieved from the Department of Pathology, Penang Hospital and analysed. The prevalence of ER positivity (55.8%), PR positivity (52.5%), c-erbB-2 oncoprotein overexpression (24%) and triple negativity (ER negative, PR negative, c-erbB-2 negative) (15%) by immunohistochemistry were comparable with other studies. Notably, c-erbB-2 overexpression was equivocal (2+) in 15% of cases. Since about a quarter of equivocal (2+) cases usually show amplification by FISH, a small but certain percentage of patients would miss the benefit of anti-c-erbB-2 antibody therapy if FISH is not performed. New ASCO/CAP guidelines on the quantitation of ER and PR will probably increase the prevalence of ER/PR positivity, invariably leading to significant ramifications on the management of patients as more patients would be deemed eligible for endocrine therapy, as well as categorisation of triple negative breast cancers.
  9. Maninderpal KG, Amir FH, Azad HA, Mun KS
    Br J Radiol, 2011 Sep;84(1005):e186-90.
    PMID: 21849361 DOI: 10.1259/bjr/66130737
    Secondary involvement of the urinary bladder in non-Hodgkin's lymphoma is relatively common; however, primary malignant lymphoma of this organ is extremely rare. The most common type of primary bladder lymphoma is a low-grade B-cell mucosa-associated lymphoid tissue (MALT) lymphoma. We report here on the imaging findings of a primary bladder lymphoma with bone marrow infiltration.
  10. Chew YK, Cheong JP, Brito-Mutunayagam S, Khir A, Prepageran N, Mun KS
    Med J Malaysia, 2011 Mar;66(1):62-3.
    PMID: 23765147
    Olfactory neuroblastoma is a rare, slow growing, malignant tumour of neuroectodermal origin that begins in neuroepithelial cells of the olfactory membrane. A metastatic rate of 20% to 60% is reported with the most common site being the cervical lymph node. Other sites include the parotid glands, skin, lungs, bone, liver, orbit, spinal cord and spinal canal. We describe a case of olfactory neuroblastoma presented to us with scalp metastasis.
  11. Thalha AM, Mahadeva S, Boon Tan AT, Mun KS
    JGH Open, 2018 Oct;2(5):242-245.
    PMID: 30483596 DOI: 10.1002/jgh3.12083
    A 33-year-old man was referred with hyperosmotic symptoms of 4 weeks. Clinical examination showed palpable hepatomegaly and no stigmata of liver disease. Findings were random glucose 16.6 mmol/L, HbA1c 12.4%, triglyceride 6.2 mmol/L, normal LFTs and ultrasound liver: increased echogenicity. Management consisted of dietician referral and commencement of metformin 500 mg bd, diamicron MR 60 mg od, and fenofibrate 145 mg od. He was non-compliant, complaining of "heaviness of head" after consuming oral diabetic agents, without symptoms of hypoglycemia. Treatment was switched to Kombiglyze XR (saxaglipitin 5 mg + metformin 1000 mg) and empagliflozin 25 mg od. He presented 1 week later with generalised pruritus with ALT 307 IU/L and serum GGT 808 IU/L. Following this, a percutaneous liver biopsy was performed, revealing steatohepatitis and marked intra-hepatic cholestasis. Kombiglyze XR was withheld, with resolution of LFTs to baseline. Phenotypes of liver injury are categorised according to R value, defined as ratio ALT/ULN:ALP/ULN. R value of ≥5:hepatocellular injury, ≤2:cholestatic injury, 2-5:mixed-type injury. Here, R value points toward mixed type (R = 3.203). Hepatotoxicity in patients with NASH is difficult to diagnose, based on laboratory parameters. Liver histology was useful in indicating additional changes apart from NASH, causing liver derangement. The Rousal Uclaf Causality Assessment Method is a scoring method to determine the probability of drug induced liver injury. RUCAM score for this case was 6 (probable adverse drug reaction). Hepatotoxicity from saxagliptin not been reported prior. Clinicians need to be more vigilant, particularly in patients with NASH.
  12. Cheng KP, Wong WJ, Hashim S, Mun KS
    J Thorac Dis, 2017 Sep;9(9):E752-E756.
    PMID: 29221336 DOI: 10.21037/jtd.2017.08.74
    Hemangiopericytomas (HPCs) are uncommon tumours. We present the case of a 41-year-old female with multiple resections at different sites over the course of 11 years. The approach considerations, as well as treatment options and prognosis are discussed. A 41-year-old female with two previous resections for intracranial meningeal HPC in 2004 and 2008, as well as adjuvant radiotherapy, presented in 2015 with left intrathoracic and left hip recurrence confirmed by positron emission tomography/computed tomography (PET/CT). She underwent left proximal femur resection/reconstruction and video-assisted thoracoscopic surgery (VATS) resection of the intrathoracic tumour was attempted. She was discharged home on her 4th post-operative day with minimal pain. There were no neurosensory or motor deficits. Any patient who has been diagnosed with HPC in the past who develops new symptoms should be worked up for recurrence, regardless of the length of disease-free interval, as our case study suggested. There has yet to be a standardized follow-up regime due to the rarity of these tumours. HPC remains a rare soft tissue sarcoma with high recurrence rate. Planned VATS evaluation and resection is possible provided complete resection with clear surgical margins can be achieved, as clear surgical margins offer the best chance of survival.
  13. Tang IP, Shashinder S, Loganathan A, Anura MM, Zakarya S, Mun KS
    Singapore Med J, 2009 Sep;50(9):e326-8.
    PMID: 19787162
    An aneurysmal bone cyst is a rare bone lesion. Its origin and precise nature remain unknown. It is seen as a locally-destructive, rapidly expandable, benign multicystic mass. We report a 17-year-old boy with an aneurysmal bone cyst of the maxilla, with extensive local involvement and bony destruction that was treated surgically. There was no recurrence noted after four years of follow-up.
  14. Alazzawi S, Sivalingam S, Raman R, Mun KS
    Ann Saudi Med, 2015 10 29;35(5):400-2.
    PMID: 26506975 DOI: 10.5144/0256-4947.2015.400
    We report an extremely rare case of mucoepidermoid carcinoma of the nasal septum. A patient with a history of right-sided nasal obstruction presented to our clinic. Clinical examination revealed a mass in the right nasal cavity originating from the nasal septum. Biopsy revealed a high-grade mucoepidermoid carcinoma. The patient was treated with surgical resection only. Surgery alone might be suitable for small tumors when direct inspection of the surgical site is feasible to detect early recurrence.
  15. Paramanantham Y, B M Said NA, Mun KS
    Malays J Pathol, 2023 Apr;45(1):19-29.
    PMID: 37119243
    INTRODUCTION: Although epithelial-mesenchymal transition (EMT) and p53 have been established to play a pivotal role in the aggressiveness of muscle-invasive bladder cancer (MIBC), its pathological correlation to cisplatin treatment in the Malaysian patient cohort is lacking. This study aimed to evaluate the association of EMT markers, e-cadherin, vimentin and actin, as well as tumour suppressor gene, p53, in cisplatin-receiving MIBC patients.

    MATERIALS AND METHODS: Formalin-fixed paraffinembedded (FFPE) blocks of muscle-invasive bladder cancer patients receiving cisplatin-based chemotherapy between January 2010 to December 2020 were traced. Immunohistochemistry staining was performed on traced blocks using antibodies to e-cadherin, vimentin and actin, and p53.

    RESULTS: p53 and e-cadherin were stained positive in most cases (p=0.515 and 0.242 respectively), although e-cadherin showed stronger positive expression in pre-cisplatin receiving MIBC cases. All the cases stained negative for actin and vimentin except for faint staining observed in one pre-cisplatin case.

    CONCLUSION: Although this study does not show a significant correlation between EMT markers and p53 with cisplatin-responsiveness in MIBC patients, the results serve as preliminary findings on the heterogeneous outcomes of molecular staining in the Malaysian MIBC patient cohort.

  16. Taib N, Yip Ch, Ranganathan S, Moosa F, Mun K
    Biomed Imaging Interv J, 2006 Jul;2(3):e30.
    PMID: 21614243 MyJurnal DOI: 10.2349/biij.2.3.e30
    Angiosarcoma of the breast is an extremely rare condition. This case illustrates the use of embolisation as a modality of treatment for primary breast angiosarcoma. No other case has been reported on the use of embolisation for this disorder.
  17. Shahrizal TA, Prepageran N, Rahmat O, Mun KS, Looi LM
    Ear Nose Throat J, 2009 Feb;88(2):786-9.
    PMID: 19224479
    Extramedullary plasmacytoma is a rare plasma cell proliferative disorder with a predilection for the head and neck region. Occasionally, it presents as a solitary lesion in the nasal cavity. We report a case of an isolated lesion in the middle turbinate of the right nasal cavity. The lesion was completely excised via an endoscopic approach. We also review the pathology and management of plasmacytomas in general.
  18. Mun KS, Cheah PL, Baharudin NB, Looi LM
    Malays J Pathol, 2006 Dec;28(2):73-7.
    PMID: 18376794 MyJurnal
    Hepatocellular carcinoma (HCC) is among the ten most common cancers in Malaysian males. As cellular proliferation is an important feature of malignant transformation, we studied the proliferation pattern of normal and benign perineoplastic liver versus hepatocellular carcinoma in an attempt to further understand the tumour transformation process. 39 HCC (21 with accompanying and 18 without cirrhosis) histologically diagnosed at the Department of Pathology, University of Malaya Medical Centre between January 1992 and December 2003 were immunohistochemically studied using a monoclonal antibody to PCNA (Clone PC10: Dako). 20 livers from cases who had succumbed to traumatic injuries served as normal liver controls (NL). PCNA labeling index (PCNA-LI) was determined by counting the number of immunopositive cells in 1000 contiguous HCC, benign cirrhotic perineoplastic liver (BLC), benign perineoplastic non-cirrhotic (BLNC) and NL cells and conversion to a percentage. The PCNA-LI was also expressed as Ojanguren et al's grades. PCNA was expressed in 10% NL, 38.9% BLNC, 76.2% BLC and 71.8% HCC with BLNC, BLC and HCC showing significantly increased (p < 0.05) number of cases which expressed PCNA compared with NL. The number of BLC which expressed PCNA was also significantly increased compared with BLNC. PCNA-LI ranged from 0-2.0% (mean = 0.2%) in NL, 0-2.0% (mean = 0.3%) in BLNC, 0-3.6% (mean = 0.7%) in BLC and 0-53.8% (mean = 7.6%) in HCC with PCNA-LI significantly increased (p < 0.05) only in HCC compared with BLC, BLNC and NL. Accordingly, all NL, BLC and BLNC showed minimal (<5% cells being immunopositive) immunoreactivity on Ojanguren et al's grading system and only HCC demonstrated immunoreactivity which ranged up to grade 3 (75% of cells). From this study, there appears to be a generally increasing trend of proliferative activity from NL to BLNC to BLC and HCC. Nonetheless, BLNC and BLC, like NL, retained low PCNA-LI and only HCC had a significantly increased PCNA-LI compared with the benign categories. This is probably related to the malignant nature of HCC and may reflect the uncontrolled proliferation of the neoplastic hepatocytes.
  19. Kong PL, Cheah PL, Mun KS, Chiew SF, Lau TP, Koh CC, et al.
    Malays J Pathol, 2020 Dec;42(3):369-376.
    PMID: 33361717
    Together with isocitrate dehydrogenase (IDH) mutation, co-deletion of 1p19q (1p19q codel) is a prerequisite for diagnosis of oligodendroglioma, making it imperative that histopathology laboratories introduce testing for 1p19q codel. To date there is still no consensus reference range and cut-offs that confirm deletion of 1p or 19q. We embarked on determining our reference range in 11 formalinfixed, paraffin-embedded non-neoplastic brain tissue using fluorescence in situ hybridisation (FISH) with the Vysis 1p36/1q25 and 19q13/19p13 FISH Probe Kit (Abbott Molecular Inc., USA). At same time we attempted to validate our methodology in 13 histologically-confirmed IDH-mutant oligodendrogliomas. For 1p, percentage cells with deletion (range=8-23%; mean±SD = 15.73±5.50%) and target: control (1p36:1q25) ratio (range = 0.89-0.96; mean±SD = 0.92±0.03) in non-neoplastic brain, differed significantly (p<0.000) from oligodendroglioma (percentage cells with deletion: range = 49-100%; mean±SD = 82.46±15.21%; target:control ratio range:0.50-0.76; mean±SD = 0.59±0.08). For 19q, percentage cells with deletion (range = 7-20%; mean±SD = 12.00±3.49%) and target:control (19q13/19p13) ratio (range:0.90-0.97; mean±SD = 0.94±0.02) in non-neoplastic brain also differed significantly from oligodendroglioma (percentage cells with deletion: range = 45-100%; mean±SD = 82.62±18.13%; target:control ratio range:0.50-0.78; mean±SD = 0.59±0.09). Using recommended calculation method, for diagnosis of 1p deletion, percentage of cells showing deletion should be >32-33% and/or target:control ratio <0.83. For 19q, percentage of cells showing deletion should be >22% and target:control ratio <0.88. Using these cut-offs all 13 oligodendroglioma demonstrated 1p19q codel.
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