Displaying publications 1 - 20 of 179 in total

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  1. pS2 expression in infiltrating ductal carcinoma of the breast correlates with oestrogen receptor positivity but not with histological grade and lymph node status
    Looi LM, Azura WW, Cheah PL, Ng MH
    Pathology, 2001 Aug;33(3):283-6.
    PMID: 11523925
    This investigation was carried out to gain insight into the prevalence of pS2 expression in invasive ductal breast carcinoma in the Malaysian population and its correlation with oestrogen receptor (ER) protein expression and tumour aggressiveness. Seventy consecutive infiltrating ductal breast carcinomas treated with mastectomy and axillary lymph node clearance were investigated, using the standard avidin-biotin complex immunoperoxidase method with microwave antigen retrieval and commercial monoclonal antibodies (Dako), for expression of pS2 and human ER. This was correlated against histological grade (modified Bloom and Richardson) and the presence of axillary lymph node metastasis of these carcinomas. Four (5.7%) were grade 1, 40 (57.1%) grade 2 and 26 (37.1%) grade 3 tumours. A total of 45 (64%) showed histological evidence of axillary lymph node metastasis. Forty (57%) were ER-positive, while 31 (44%) were pS2-positive. There was a statistically significant correlation between pS2 and ER expressions (chi2-test with Yates correction: P<0.005). There was no correlation between pS2 expression and histological grade (P>0.1) and the presence of lymph node metastasis (P>0.1). Our findings support the views that pS2 may be a co-marker of endocrine responsiveness in invasive breast cancer and that it does not influence breast cancer biology in terms of potential for metastatic spread.
  2. Fulltext p53: an overview of over two decades of study
    Cheah PL, Looi LM
    Malays J Pathol, 2001 Jun;23(1):9-16.
    PMID: 16329542
    p53 is the most commonly mutated gene in human cancers. It encodes a 53 kilodalton protein with several evolutionarily conserved domains viz sequence-specific DNA binding, tetramerisation, SH3 molecule binding, C-terminal and N-terminal. Existing in the cell at a very low level and in a relatively inactive form, p53 protein is increased and activated during periods of cellular stress. Unlike other proteins, the increase in protein level and its activation result from modification of the protein rather than genetic transcriptional or translational upregulation. Normally, Mdm2 protein interacts with p53 protein and effectively targets it for ubiquitin proteolysis within an autoregulatory feedback loop. Phosphorylation at the N-terminus reduces p53 interaction with Mdm2 with a resultant increase in p53 protein level. Modification at the C and N termini via phosphorylation or acetylation upregulates binding to specific DNA targets increasing transcription of these downstream genes. The net effect of p53 protein increase and activation lies in arrest of the cell in cycle which allows time for repair of the incurred damage or apoptosis or death of the cell. Failure of these normal protective and adaptive mechanisms caused by mutation of the p53 gene with product of an abnormal protein, loss of p53 protein through interaction with and degradation by HPV E6 protein or overexpressed Mdm2 etc. permits DNA-damaged cells to continue replicating. Left unchecked, this frequently contributes to tumourigenesis. Various methods have been devised to screen for mutations of the p53 gene, still the most common source of failed p53 mechanism. These include immunohistochemical detection of mutated proteins or identification of altered electrophoretic mobility of mutated p53 sequences. Sequencing of the gene nonetheless remains the most accurate method for determination of mutation. Major advances have been made in p53 research but the most meaningful probably lies in the promising results achieved in tumour therapy where introduction of wild type p53 gene has resulted in regression of non-small-cell lung cancer (NSCLC). Many other notable developments in this field include description of p53 homologues, "gain of function" mutants, p53 polymorphisms, angiogenesis-inhibiting properties of wild type p53 protein etc.
  3. p16(INK4a) is a useful marker of human papillomavirus integration allowing risk stratification for cervical malignancies
    Cheah PL, Looi LM, Teoh KH, Mun KS, Nazarina AR
    Asian Pac J Cancer Prev, 2012;13(2):469-72.
    PMID: 22524808
    The present study was conducted to assess utility of p16(INK4a) immunopositivity as a surrogate marker for genomic integration of high-risk human papillomavirus infection (hrHPV). A total of 29 formalin-fixed, paraffin-embedded cervical low-grade squamous intraepithelial lesions (LSILs), 27 high-grade squamous intraepithelial lesions (HSILs) and 53 invasive squamous cell carcinomas (SCCs), histologically-diagnosed between 1st January 2006 to 31st December 2008 at the University of Malaya Medical Centre were stained for p16(INK4a) (CINtec Histology Kit (REF 9511, mtm laboratories AG, Heidelberg, Germany). Immunopositvity was defined as diffuse staining of the squamous cell cytoplasm and or nucleus (involving > 75% of the intraepithelial lesions or SCCs). Staining of basal and parabasal layers of intraepithelial lesions was pre-requisite. One (3.4%) LSIL, 24 (88.9%) HSIL and 46 (86.8%) SCC were p16(INK4a) immunopositive. All normal squamous epithelium did not express p16(INK4). p16(INK4a) expression was significantly lower (p<0.05) in LSIL compared with HSIL and SCC with no difference in expression between HSIL and SCC.The increased p16(INK4a) immunopositivity in HSIL and SCC appears in line with the integrated existence of the hrHPV and may provide more insightful information on risk of malignant transformation of cervical squamous intraepithelial lesions than mere hrHPV detection.
  4. alpha1-Antitrypsin deficiency is not an important cause of childhood liver diseases in a multi-ethnic Southeast Asian population
    Lee WS, Yap SF, Looi LM
    J Paediatr Child Health, 2007 Sep;43(9):636-9.
    PMID: 17688648
    We conducted a prospective study to determine the role of alpha1-antitrypsin (alpha1AT) deficiency in the pathogenesis of neonatal cholestasis and other childhood liver diseases in a multi-ethnic Southeast Asian population.
  5. Wilms' tumour in Malaysian children: a histopathological study of cases encountered at the University Hospital, Kuala Lumpur over a 22-year period
    Cheah PL, Looi LM, Lin HP
    Malays J Pathol, 1992 Dec;14(2):111-5.
    PMID: 1338998
    Formerly thought to have a constant incidence rate throughout the world, Wilms' tumour (nephroblastoma) has been shown to be less common among Asian children. A retrospective demographic and morphological study of Wilms' tumour histologically diagnosed over a 22-year period at the Department of Pathology, University Hospital, Kuala Lumpur was conducted to assess for inherent demographic and morphological differences between tumours in Malaysian children and those of Western populations. Thirty-seven cases of histologically proven Wilms' tumour qualified for inclusion in this study. 19 patients were Chinese, 13 Malay, 4 Indian and 1 Anglo-asian. 21 were male and 16 were female (M:F ratio = 1.3:1). Their ages ranged from 1 month to 4 years. 70.3% of the patients were below 2 years of age. 36 cases had unilateral and 1 bilateral tumours. Of unilateral tumours, 19 involved the left kidney and 17 the right. Histological assessment, based on criteria of the National Wilms' Tumor Study Group, revealed 20 (52.6%) tumours with a mixed pattern while 8 (21.1%) showed epithelial, 7 (18.4%) blastemal and 3 (7.8%) stromal-predominant patterns. Anaplasia was observed in only 2 tumours (5.3%). There was no obvious difference in age range and sex distribution, laterality of tumours and incidence of anaplasia between this and Western studies. No ethnic predilection was observed. A notably larger percentage of cases were below 2 years of age. Also, a larger proportion of epithelial-predominant and a lower proportion of blastemal-predominant tumours was observed compared with patterns reported from Western populations.
  6. Fulltext Usefulness of a scoring system in the interpretation of histology in neonatal cholestasis
    Lee WS, Looi LM
    World J Gastroenterol, 2009 Nov 14;15(42):5326-33.
    PMID: 19908342 DOI: 10.3748/wjg.15.5326
    AIM: To ascertain the usefulness of a histological scoring system devised to assist in the interpretation of liver histology in neonatal cholestasis (NC).

    METHODS: Liver biopsy specimens obtained from infants with NC referred to a tertiary pediatric unit in Malaysia were prospectively studied. The first author, blinded to the final diagnosis, devised the histological diagnosis based on a 7-feature (portal ductal proliferation, bile plugs in portal ductules, porto-portal bridging, lymphocytic infiltration in portal region, multinucleated hepatocytes, neutrophilic infiltration, hepatocellular swelling), 15-point (0 to 15) scoring system. The author classified the histological diagnosis as either biliary atresia (BA) or neonatal hepatitis (NH, all other diagnoses), and subsequently compared the author's diagnosis with the final diagnosis.

    RESULTS: Eighty-four biopsy specimens obtained from 78 patients were reviewed. Without the scoring system, BA was correctly diagnosed by the author histologically in 30 cases, labelled as NH in 3. For other diagnoses, BA was excluded correctly in 33 cases and mislabeled as BA in 2 cases. The overall sensitivity for BA was 91%, specificity 86% and accuracy 88%. With the scoring system, a score of >or=7 had the best diagnostic utility to differentiate BA from other intrahepatic cholestasis histologically (sensitivity 88%, specificity 94%, accuracy 92%). Four patients with a score<7 had BA, and 3 patients with a score>or=7 had NH.

    CONCLUSION: A 7-feature, 15-point histological scoring system had good diagnostic accuracy in the interpretation of liver histology in neonatal cholestasis.
  7. Fulltext Unusual finding of endocervical-like mucinous epithelium in continuity with urothelium in endocervicosis of the urinary bladder
    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.
  8. Fulltext Universal health coverage and intersectoral action for health: key messages from Disease Control Priorities, 3rd edition
    Jamison DT, Alwan A, Mock CN, Nugent R, Watkins D, Adeyi O, et al.
    Lancet, 2018 03 17;391(10125):1108-1120.
    PMID: 29179954 DOI: 10.1016/S0140-6736(17)32906-9
    The World Bank is publishing nine volumes of Disease Control Priorities, 3rd edition (DCP3) between 2015 and 2018. Volume 9, Improving Health and Reducing Poverty, summarises the main messages from all the volumes and contains cross-cutting analyses. This Review draws on all nine volumes to convey conclusions. The analysis in DCP3 is built around 21 essential packages that were developed in the nine volumes. Each essential package addresses the concerns of a major professional community (eg, child health or surgery) and contains a mix of intersectoral policies and health-sector interventions. 71 intersectoral prevention policies were identified in total, 29 of which are priorities for early introduction. Interventions within the health sector were grouped onto five platforms (population based, community level, health centre, first-level hospital, and referral hospital). DCP3 defines a model concept of essential universal health coverage (EUHC) with 218 interventions that provides a starting point for country-specific analysis of priorities. Assuming steady-state implementation by 2030, EUHC in lower-middle-income countries would reduce premature deaths by an estimated 4·2 million per year. Estimated total costs prove substantial: about 9·1% of (current) gross national income (GNI) in low-income countries and 5·2% of GNI in lower-middle-income countries. Financing provision of continuing intervention against chronic conditions accounts for about half of estimated incremental costs. For lower-middle-income countries, the mortality reduction from implementing the EUHC can only reach about half the mortality reduction in non-communicable diseases called for by the Sustainable Development Goals. Full achievement will require increased investment or sustained intersectoral action, and actions by finance ministries to tax smoking and polluting emissions and to reduce or eliminate (often large) subsidies on fossil fuels appear of central importance. DCP3 is intended to be a model starting point for analyses at the country level, but country-specific cost structures, epidemiological needs, and national priorities will generally lead to definitions of EUHC that differ from country to country and from the model in this Review. DCP3 is particularly relevant as achievement of EUHC relies increasingly on greater domestic finance, with global developmental assistance in health focusing more on global public goods. In addition to assessing effects on mortality, DCP3 looked at outcomes of EUHC not encompassed by the disability-adjusted life-year metric and related cost-effectiveness analyses. The other objectives included financial protection (potentially better provided upstream by keeping people out of the hospital rather than downstream by paying their hospital bills for them), stillbirths averted, palliative care, contraception, and child physical and intellectual growth. The first 1000 days after conception are highly important for child development, but the next 7000 days are likewise important and often neglected.
  9. Fulltext Tuberculosis or systemic lupus erythematosus? A diagnostic and therapeutic dilemma
    Mohd A, Goh EM, Chow SK, Looi LM, Yeap SS
    Southeast Asian J. Trop. Med. Public Health, 2003 Jun;34(2):361-4.
    PMID: 12971563
    The diagnosis of patients with fever of unknown origin (FUO) is often problematic because the range of possible differential diagnoses is broad. We report on a case in which a patient presented with FUO and was subsequently found to have both a collagen vascular disease and an intercurrent infection. Treatment for the collagen vascular disease with corticosteroids exacerbated the intercurrent infection. The problems in the diagnosis and management of such cases are discussed.
  10. Treatment of data in the study of elemental concentration of biological materials
    Ng KH, Bradley DA, Looi LM
    Appl Radiat Isot, 1995 6 1;46(6-7):629-30.
    PMID: 7633385
  11. Tissue microarray immunohistochemical profiles of p53 and pRB in hepatocellular carcinoma and hepatoblastoma
    Azlin AH, Looi LM, Cheah PL
    Asian Pac J Cancer Prev, 2014;15(9):3959-63.
    PMID: 24935581
    The tumour suppressor genes, p53 and pRb, are known to play important roles in neoplastic transformation. While molecular routes to the uncontrolled growth of hepatocytes, leading to primary liver cancer have generated considerable interest, the roles of p53 and pRb mutations in hepatocellular carcinoma (HCC) and hepatoblastoma (HB) remain to be clarified. We examined the immunohistochemical expression of p53 and pRb gene products in 26 HCC and 9 HB, sampled into tissue microarray blocks. 10 (38%) of 26 HCC showed > 10% tumour nuclear staining for p53 protein, 3 of these also being HbsAg positive. Conversely, none of 9 HB expressed nuclear p53 immunopositivity. Some 24 (92%) HCC and 8 (89%) HB showed loss of pRb nuclear expression. Two of the 26 HCC and one of the 9 HB showed >10% tumour nuclear staining for pRb protein. Our results suggest that p53 does not have an important role in the development of HB but may contribute in HCC. There is also loss of pRb expression in the majority of HCC and HB, supporting loss of pRb gene function in the hepatocarcinogenesis pathway. However, a comparison of the staining profiles of p53 and pRb proteins in HCC and HB did not reveal a consistent pattern to differentiate between the two types of tumours immunohistochemically. Hence the use of p53 and pRB protein expression has no contribution in the situation where there is a diagnostic difficulty in deciding between HCC and HB.
  12. Fulltext The pattern of renal disease in Malaysia
    Looi LM
    Malays J Pathol, 1994 Jun;16(1):19-21.
    PMID: 16329571
    An analysis of 1000 consecutive, adequate renal biopsies from patients of the University Hospital Kuala Lumpur between 1982 and 1991 revealed: minimal change nephritis (20.7%), focal glomerulosclerosis (2.9%), proliferative glomerulonephritides (16.0%), membranous glomerulonephritis (5.5%), IgA nephropathy (18.5%), lupus nephritis (24.9%), end stage nephropathy (3.1%) and others (8.4%). Compared with the previous decade, IgA nephropathy has emerged as a common entity. Lupus nephritis forms the largest diagnostic entity and is probably related to the selected referral of SLE patients to this hospital.
  13. The pattern of amyloidosis in a Malaysian patient population
    Looi LM
    Histopathology, 1991 Feb;18(2):133-41.
    PMID: 1901294
    Congo red screening of 27,052 routine biopsy specimens from 22,827 patients over a 5 1/2-year period in the Department of Pathology, University of Malaya detected 186 cases of amyloidosis. The categories of amyloidosis encountered and their prevalences in relation to each other were: systemic AL (5.9%); systemic AA (3.2%); isolated atrial (14%); primary localized cutaneous (7.5%); other primary localized deposits (3.2%); localized intratumour (58%); and dystrophic (8.6%). A third of patients with systemic AL amyloidosis had coexistent immunocyte abnormality. The commonest underlying pathology for systemic AA amyloidosis was leprosy. Notable among the types of localized amyloidosis revealed by this study were isolated atrial amyloidosis, which appeared to complicate chronic rheumatic heart disease, and intratumour amyloidosis complicating nasopharyngeal carcinoma. Other tumours in which amyloid deposits were observed included basal cell carcinoma, islet cell tumour and medullary carcinoma of the thyroid. Dystrophic amyloidosis was observed in fibrotic tissues, such as damaged cardiac valves and osteoarthritic joints. Heredofamilial amyloidosis, senile systemic amyloidosis and degenerative cerebral amyloidosis were notably absent from this study.
  14. The pattern of amyloidosis in Malaysia
    Looi LM
    Malays J Pathol, 1994 Jun;16(1):11-3.
    PMID: 16329569
    Congo red screening of routine biopsies at the University Hospital Kuala Lumpur revealed the following categories of amyloidosis: systemic AL (5.9%); systemic AA (3.2%); isolated atrial (14%); primary localized cutaneous (7.5%); other primary localized deposits (3.2%); localized intratumour (58%); and dystrophic (8.6%). Unlike in the West, AA amyloidosis in this population was usually secondary to leprosy or tuberculosis. Liver involvement in AL amyloidosis was shown to exhibit a sinusoidal pattern and differed from the vascular pattern of AA amyloidosis. Within the category of AA amyloidosis, there were two patterns of renal involvement--glomerular and vascular, with the glomerular pattern carrying a more ominous clinical picture. Notable among the localized amyloidoses were isolated atrial amyloidosis complicating chronic rheumatic heart disease, intratumour amyloidosis within nasopharyngeal carcinomas and dystrophic amyloidosis which occurred in fibrotic tissues.
  15. Fulltext The pattern of amyloid deposition in the lung
    Looi LM
    Malays J Pathol, 1999 Jun;21(1):29-35.
    PMID: 10879276
    A review of routine histopathological samples and autopsies examined at the Department of Pathology, University of Malaya revealed 15 cases of amyloidosis of the lung. Two were localized depositions limited to the lung while in the remainder, lung involvement was part of the picture of systemic amyloidosis. Both cases of localized amyloidosis presented with symptomatic lung/bronchial masses and a clinical diagnosis of tumour. Histology revealed "amyloidomas" associated with heavy plasma cell and lymphocytic infiltration and the presence of multinucleated giant cells. In both cases, the amyloid deposits were immunopositive for lambda light chains and negative for kappa chains and AA protein. One was a known systemic lupus erythematosus patient with polyclonal hypergammaglobulinaemia. The other patient was found to have plasma cell dyscrasia with monoclonal IgG lambda gammopathy. Both patients did not develop systemic amyloidosis. In contrast, lung involvement in systemic AA amyloidosis was not obvious clinically or macroscopically but was histologically evident in 75% of cases subjected to autopsy. Amyloid was detected mainly in the walls of arterioles and small vessels, and along the alveolar septa. It was less frequently detected in the pleura, along the basement membrane of the bronchial epithelium and around bronchial glands. In one case of systemic AL amyloidosis associated with multiple myeloma, an "amyloidoma" occurred in the subpleural region reminiscent of localized amyloidosis. These cases pose questions on (1) whether localized "tumour-like" amyloidosis is a forme fruste of systemic AL amyloidosis and (2) the differing pattern of tissue deposition of different chemical types of amyloid fibrils, with the suggestion that light chain amyloid has a greater tendency to nodular deposition than AA amyloid.
  16. The pathology of the nephrotic syndrome in Malaysians
    Prathap K, Looi LM, Lam KL, Wang F, Chua CT
    Malays J Pathol, 1983 Aug;6:39-49.
    PMID: 6599867
  17. The histopathology laboratory services in Malaysia
    Looi LM
    Malays J Pathol, 1983 Aug;6:15-9.
    PMID: 6599864
  18. Fulltext The histopathological pattern of primary IgA nephropathy in a Malaysian patient population
    Peh SC, Looi LM, Wang F, Chua CT, Tan HW, Lam KL
    Malays J Pathol, 1990 Jun;12(1):21-6.
    PMID: 2090886
    In the 10-year period from October 1977 to July 1987, 149 cases of primary IgA nephropathy were histologically confirmed through renal biopsies in the Department of Pathology, University Hospital, Kuala Lumpur. The ages of these patients ranged from 5 to 72 years, with the majority in the 20-30 year age group. There was no sex preponderance. The ethnic distribution showed a significant predominance of Chinese with 107 (71.8%) Chinese, 24 (16.1%) Malays, 15 (10.1%) Indians and 3 others. A wide range of renal glomerular pathology was seen, the commonest being diffuse mesangioproliferative glomerulonephritis (59.1%). Focal proliferative glomerulonephritis (14.1%) followed by minimal change glomerulonephritis (10.7%) were next in order of frequency. Immunofluorescence studies consistently demonstrated heavy and predominant IgA deposition in the mesangium. Weak deposition of C3, IgG and IgM were also observed in various combinations.
  19. Fulltext The association between methods of biopsy and survival following breast cancer: A hospital registry based cohort study
    Kong YC, Bhoo-Pathy N, O'Rorke M, Subramaniam S, Bhoo-Pathy NT, See MH, et al.
    Medicine (Baltimore), 2020 Feb;99(6):e19093.
    PMID: 32028433 DOI: 10.1097/MD.0000000000019093
    Percutaneous biopsy in breast cancer has been associated with an increased risk of malignant cell seeding. However, the importance of these observations remains obscure due to lack of corroborating evidence from clinical studies. We determined whether method of biopsy is associated with breast cancer survival. This hospital registry-based cohort study included 3416 non-metastatic breast cancer patients diagnosed from 1993 to 2011 in a tertiary setting. Factors associated with biopsy methods were assessed. Multivariable Cox regression analysis was used to determine the independent prognostic impact of method of biopsy. Overall, 990 patients were diagnosed by core needle biopsy (CNB), 1364 by fine needle aspiration cytology (FNAC), and 1062 by excision biopsy. Excision biopsy was significantly associated with more favorable tumor characteristics. Radiotherapy modified the prognostic impact of biopsy method (Pinteraction 
  20. The Top 25 Laboratory Tests by Volume and Revenue in Five Different Countries
    Horton S, Fleming KA, Kuti M, Looi LM, Pai SA, Sayed S, et al.
    Am J Clin Pathol, 2019 04 02;151(5):446-451.
    PMID: 30535132 DOI: 10.1093/ajcp/aqy165
    OBJECTIVES: To compare the most common diagnostic/laboratory tests across five different referral hospitals by volume and revenue.

    METHODS: The authors obtained data on volumes and reimbursement rates for the most common 25 tests at the five hospitals with which they are affiliated and organized them to be as comparable as possible. Simple descriptive statistics were used to make cross-country comparisons.

    RESULTS: There are strong similarities across all five hospitals in the top five tests by both volume and revenue. However, the top five by volume differ from the top five by revenue. Reimbursement rates also follow common patterns, being lowest for the most common biochemical test; intermediate for the most common hematology and microbiology tests, respectively; and highest for the most common pathology test.

    CONCLUSIONS: Most of the most common tests also appear in the new Essential Diagnostics List. This may inform plans for universal health coverage.

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