Displaying publications 41 - 60 of 179 in total

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  1. Looi LM, Cheah PL
    Hum Pathol, 1997 Jul;28(7):847-9.
    PMID: 9224755
    A retrospective study was conducted to investigate whether there was a correlation between the histological pattern of renal amyloidosis, the chemical type of amyloid protein involved and the clinical presentation. Eighteen consecutive cases of systemic amyloidosis that had renal biopsies processed and examined histopathologically at the Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur were reviewed. The age range of patients was 25 to 64 yrs (mean, 46 yrs). The male:female ratio was 2.6:1. Three patients were Malay, 9 Chinese, 3 Indian, 1 Indonesian, 1 Iban, and 1 Bisaya. According to the predominant site of amyloid deposition, 14 cases showed a glomerular pattern and 4 a vascular pattern. 8 cases were designated as 2 anti-human amyloid-A (AA) amyloidosis on the basis of permanganate-sensitivity and immunoreactivity of deposits with anti-human AA protein antibody. Ten cases contained deposits that were permanganate-resistant and nonimmunoreactive for AA protein and were designated as AL in type. The histomorphologic pattern of renal amyloidosis did not provide a reliable means of differentiating AA from AL amyloidosis. The glomerular pattern tended to present with renal manifestations such as nephrotic syndrome and chronic renal failure, whereas the vascular pattern tended to present with nonrenal manifestations such as diarrhoea. These findings may have a bearing on the pathophysiology of amyloidosis and provide clues to appropriate management.
  2. Looi LM, Cheah PL
    Malays J Pathol, 1992 Dec;14(2):69-76.
    PMID: 1304627
    In situ hybridisation (ISH) is based on the complementary pairing of labelled DNA or RNA probes with normal or abnormal nucleic acid sequences in intact chromosomes, cells or tissue sections. Compared with other molecular biology techniques applicable to anatomical pathology, ISH enjoys better rapport with histopathologists because of its similarity to immunohistochemistry. It has the unique advantage over other molecular biology techniques--largely based on probe hybridisation with nucleic acid extracted from homogenised tissue samples--of allowing localisation and visualisation of target nucleic acid sequences within morphologically identifiable cells or cellular structures. Probes for ISH may bear radioactive or non-radioactive labels. Isotopic probes (3H, 32P, 35S, 125I) are generally more sensitive than non-isotopic ones but are less stable, require longer processing times and stringent disposal methods. Numerous non-isotopic labels have been used; of these biotin and digoxigenin are the reporters of choice. Optimised non-isotopic systems of equivalent sensitivity to those which use radioactive-labelled probes have been described. In ISH, finding the optimal balance between good morphological preservation of cells and strong hybridisation signals is crucial. Tissue fixation and retention of cytoskeletal structures, unfortunately, impede diffusion of probes into tissues. ISH sensitivity is also influenced by inherent properties of the probe and hybridisation conditions. Although ISH is largely a research tool, it is already making strong inroads into diagnostic histopathology. It has been applied for the detection of various infective agents particularly CMV, HPV, HIV, JC virus, B19 parvovirus, HSV-1, EBV, HBV, hepatitis delta virus, Chlamydia trachomatis, salmonella and mycoplasma in tissue sections.(ABSTRACT TRUNCATED AT 250 WORDS)
  3. Tan PE, Looi LM
    Malays J Pathol, 1991 Dec;13(2):101-4.
    PMID: 1823090
    Although most anatomical pathologists have encountered breast lesions with the composite histological features of fibroadenoma (FA) and fibrocystic change (FC), referred to as fibroadenomatosis or fibroadenomatoid mastopathy (FAM), little is known about its prevalence or clinico-pathological significance. In a retrospective histological review of 400 consecutive breast lesions, among both East and West Malaysians, coded either as FA or FC in the files of the Department of Pathology, University of Malaya, we found 45 (11.3%) cases of FAM. Typically, FAM lesions showed fibroadenomatoid foci in a background of fibrocystic change. The finding of FAM among lesions coded as FC was higher (18.5%) than among FA (4%). The mean age of patients with FAM (32.1 years) was similar to FC (35.1 years) but significantly older than that of FA (26.1 years). The notion that FA and FC are lesions at two ends of a spectrum of growth disorder of breast related to oestrogen-progesterone interplay, and that FAM occupies a position intermediate between the two, may explain its morphological and age patterns, but remains speculative. It is hoped that increasing awareness of this condition will lead to better understanding of breast pathophysiology. Nevertheless, until its biological nature, histogenesis and malignant potential are more clearly understood, defining FAM as a distinct form of breast disease may not be meaningful to patient management.
  4. Cheah PL, Looi LM
    Pathology, 2002 Aug;34(4):326-31.
    PMID: 12190289
    AIMS: The pattern of p53 expression was studied in pre-invasive and invasive cervical carcinoma in an attempt to clarify its role in cervical carcinogenesis.

    METHODS: A total of 234 invasive cervical carcinomas (152 squamous cell carcinomas, 61 adenocarcinomas and 21 adenosquamous carcinomas) and 16 cervical intraepithelial neoplasia (CIN) I, six CIN II and 25 CIN III were immunohistochemically studied for p53.

    RESULTS: p53 was detected more frequently in CIN and invasive carcinoma (100% of CIN I, 74.2% CIN II + III and 70.1% invasive carcinoma) compared with benign cervices (P< 0.001); however, only three squamous cell carcinomas, 11 adenocarcinomas and two adenosquamous carcinomas exhibited p53 expression in >75% of tumour nuclei. Six of the 11 adenocarcinomas and both adenosquamous carcinomas were poorly differentiated compared with one of the three squamous carcinomas. p53 immunoreactive cells were randomly distributed in invasive carcinoma, confined to the lower third of the epithelium in CIN I, reached the middle third in 20% of CIN II and upper third in 16.6% of CIN III.

    CONCLUSIONS: Assuming that p53 immunoreactivity indicates gene mutation when the majority (> 75%) of neoplastic cells express p53, p53 mutations would seem uncommon in cervical carcinogenesis. Nonetheless, glandular malignancies, in particular poorly differentiated variants, may show a higher frequency of mutation. p53 was detected more frequently in CIN I compared with CIN II/III and invasive carcinoma which may be due to p53 protein degradation following interaction with high risk human papillomavirus E6 protein in CIN II/III and invasive carcinoma.

  5. Cheah PL, Looi LM
    Pathology, 1996 Aug;28(3):229-31.
    PMID: 8912350
    Eight histologically-confirmed cases of clear cell sarcoma of the kidney (CCSK) were studied for possible mutations in the p53 tumor suppressor gene by the immunohistochemical demonstration of mutant p53 proteins using a monoclonal (DO7: Dako) and a polyclonal (AB565: Chemicon) antibody to p53 protein. All cases exhibited p53 protein nuclear immunopositivity, although in varying numbers of tumor cells and with different staining intensities. p53 protein (DO7 or AB565) was expressed in < 25% of the tumor cells in four (50%) of the cases, including the one case with a known long term survival of 13 years from the time of diagnosis. The other tumors showed p53 protein immunopositivity in > 25% of the tumor cells when stained with either DO7 or AB565 or both. The intensity of staining, graded on visual impression into weak, moderate or strong, did not correlate well with the ratio of positive staining tumor cells. While this study is unable to clarify the relative prevalence and importance of p53 mutational events in the pathogenesis of this aggressive renal tumor of childhood, it is reasonably suggestive that alterations in the p53 tumor suppressor gene do occur in CCSK.
  6. Cheah PL, Looi LM
    Pathology, 1994 Apr;26(2):115-8.
    PMID: 8090580
    Examination of routinely stained haematoxylin and eosin sections may sometimes prove inadequate in differentiating partial hydatidiform moles (PHM) from complete hydatidiform moles (CHM). While cytogenetic analysis can aid in the distinction, such facilities are not always available. The possibility of using immunohistochemistry to aid in the differentiation was studied. Twenty-five histologically proven CHM and 11 PHM were studied for their patterns of expression of human chorionic gonadotrophin (hCG), human placental lactogen (hPL) and placental alkaline phosphatase (PIAP). All CHM stained diffusely with hCG and focally with both hPL and PIAP irrespective of gestational age. Of PHM, 63.6% were diffusely positive for hCG, 27.3% for hPL and 54.5% for PIAP; the rest were focally positive. The hCG pattern changed from diffuse to focal with increasing gestational age of PHM, while those of hPL and PIAP became increasingly diffuse with gestational age. While these protein expressions may be applied in differentiating late PHM from CHM, it is not useful in first trimester cases. The most helpful application is that focal expression of hCG and diffuse expressions of hPL and PIAP is not seen in CHM, thereby excluding such a diagnosis. PHM, in contrast, can show either diffuse or focal expression of all 3 antigens.
  7. Looi LM, Cheah PL
    Pathology, 1993 Apr;25(2):106-9.
    PMID: 8396229
    This study explores immunohistochemical characteristics that may be of diagnostic value in differentiating clear cell sarcoma of the kidney (CCSK) from Wilms' tumor (WT) and may provide some insight into the histogenesis of CCSK. Formalin-fixed, paraffin-embedded sections of 8 CCSK and 9 WT were stained, using the standard avidin-biotin peroxidase complex method, for vimentin (VIM), Factor-8 related antigen (F8A), epithelial membrane antigen (EMA), desmin (DES), S-100 protein and Mac 387. CCSK cells consistently exhibited moderate to strong diffuse cytoplasmic positivity for VIM and were negative for F8A, EMA, DES, S-100 and Mac 387. In contrast, only patchy groups of stromal cells and primitive glomeruloid structures in WT exhibited VIM-positivity. Blastemal cells were VIM-negative. Stromal cells with rhabdomyomatous differentiation exhibited cytoplasmic positivity for DES. Epithelial cells of maturing tubular structures showed EMA-positivity whereas immature tubular structures were EMA-negative. Neither blastemal, stromal nor epithelial elements in WT were positive for F8A, S-100 or Mac 387. Podocytes and mesangial cells of glomeruli in 3 mid-trimester human abortuses (controls) exhibited moderate to strong VIM-positivity. The importance of differentiating CCSK from WT has been repeatedly emphasized because of its poorer prognosis and the necessity of adding Adriamycin to the chemotherapeutic regime. The consistent VIM-positivity of CCSK cells can be a useful feature in differentiating it from "blastemal-predominant" WT, with which it is often confused. Although vimentin expression by CCSK cells is consistent with a mesenchymal character, the possibility of a histogenetic link with glomerular podocytes or mesangial cells should also be considered.
  8. 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.
  9. Looi LM, Wong LX, Koh CC
    Malays J Pathol, 2015 Dec;37(3):213-8.
    PMID: 26712665 MyJurnal
    In June 2015, invitations were sent by email to 151 APAME journals to participate in an online survey with an objective of gaining insight into the common publication misconduct encountered by APAME editors. The survey, conducted through SurveyMonkey over a 20-day-period, comprised 10 questions with expansions to allow anecdotes limited to 400 characters, estimated to take less than 10 minutes to complete. Only one invitation was issued per journal, targeting (in order of priority) editors, editorial board members and editorial staff, and limited by email availability. 54 (36%) journals responded. 98% of respondents held Editor or Editorial Board positions. All respondent journals have editorial policies on publication ethics and 96% provide instructions related to ethics. 45% use anti-plagiarism software to screen manuscripts, the most popular being iThenticate, CrossCheck and Turnitin. Up to 50% of journals had encountered studies without IRB approval. Author misconduct encountered were (in rank order): plagiarism (75%), duplicate publication (58%), unjustified authorship (39%), authorship disputes (33%), data falsification (29%), data/image manipulation (27%), conflict of interest (25%), copyright violation (17%) and breach of confidentiality (10%). Reviewer misconduct encountered were: conflict of interest (19%), plagiarism (17%), obstructive behavior (17%), abusive language (13%) and breach of confidentiality (13%). Notwithstanding the limitations of the survey and the response rate, a few insights have been gained: (1) the need for strengthening the ethical culture of researchers/authors and reviewers, (2) anti-plagiarism software can improve plagiarism detection by about 15%, and (3) the need for technical support to detect plagiarism, duplicate publication and image manipulation.
  10. Chow TK, Looi LM, Cheah PL
    Malays J Pathol, 2015 Dec;37(3):239-46.
    PMID: 26712669
    BACKGROUND: In the past, lupus nephritis was histologically classified according to the 1995 WHO Classification. With the introduction of the 2003 ISN/RPS Classification, many nephropathology services converted to this new classification. This study was undertaken to compare both classification systems in a single centre practice.
    METHODS: 103 consecutive adequate renal biopsies initially reported as lupus nephritis in the Department of Pathology, Faculty of Medicine, University of Malaya were reassessed using the criteria of both the 1995 WHO Classification and the 2003 ISN/ RPS Classification.
    RESULTS: The relative prevalence for each class using the WHO Classification were: Class I (1%), Class II (8.7%), Class III (6.8%), Class IV (60.2%), Class V (20.4%), Class VI (2.9%) while the prevalence using the 2003 ISN/RPS Classification were: Class I (1%), Class II (8.7%), Class III (6.8%), Class IV (61.2%), Class V (21.3%), Class VI (1%). Both classifications were essentially comparable with regards to Classes I, II and III. The differences in Classes IV, V and VI were significant in potential to alter patient management. The identification of segmental lesions (Class IV-S) over and above a global nephritis (Class IV-G) deserves more focused clinicopathological studies to gauge whether these groups have different clinical manifestations and outcomes. With regards Class V, the ISN/RPS system, by requiring that all mixed classes be stipulated in the diagnostic line, minimizes the chances of patients missing out on additional treatment. The ISN/ RPS system has stricter criteria for Class VI, which again minimizes patients missing out on therapy. On the whole, the ISN/RPS system is more user-friendly as criteria are more clearly defined which translates to more benefits to patient care.
    Study site: Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  11. 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. Tang IP, Singh S, Krishnan G, Looi LM
    J Laryngol Otol, 2012 Dec;126(12):1284-6.
    PMID: 23084156 DOI: 10.1017/S0022215112002435
    We report a rare case of small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses with intracranial extension, and discuss the management of this rare tumour.
  13. Cheah PL, Looi LM, Sivanesaratnam V
    J Obstet Gynaecol Res, 2011 Jun;37(6):489-95.
    PMID: 21349124 DOI: 10.1111/j.1447-0756.2010.01386.x
    With cervical carcinoma remaining the second leading cancer among Malaysian women, it is imperative to clarify the prevalence of human papillomavirus (HPV) in this respect, considering the dearth of local information.
  14. Lee WS, Chai PF, Looi LM
    Med J Malaysia, 2009 Sep;64(3):216-9.
    PMID: 20527271
    Progressive familial intrahepatic cholestasis (PFIC) is characterized by early onset cholestasis, progressive liver cirrhosis, pruritus, poor growth and inexorable progression to liver cirrhosis in early childhood. The serum level of gamma-glutamyl transferase is low or normal, which is discordant with severe cholestasis. Five Malaysian patients with PFIC, who all had typical features of PFIC with early onset of severe and progressive cholestasis, pruritus, cirrhosis and liver failure, were described. Three patients died as a result of the disease, while another one died due to post-liver transplant complication. The only survivor has compensated liver cirrhosis. Patients with severe cholestasis but has spuriously low yGT should be suspected of having PFIC. Liver transplant, which is life-saving in a majority of patients with PFIC, should be considered in all patients with PFIC.
  15. Chan SH, Ng C, Looi LM
    ANZ J Surg, 2008 Sep;78(9):775-9.
    PMID: 18844907 DOI: 10.1111/j.1445-2197.2008.04648.x
    Isosulfan blue is not available for clinical use in Malaysia. This study describes the use of methylene blue as an alternative to isosulfan blue in colorectal sentinel node mapping.
  16. 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.
  17. Looi LM, Ng MH, Cheah PL
    Malays J Pathol, 2007 Jun;29(1):33-5.
    PMID: 19105326 MyJurnal
    The unique ability of tumour cells to proliferate indefinitely is crucial to neoplastic progression as it allows these cells to express the aggressive properties of cancer without the censure of physiological ageing. This is in contrast to normal somatic cells which are subject to a "mitotic clock," a phenomenon that has been linked to telomeric shortening after each round of cell replication, so that eventually the loss of genetic material reaches a critical stage and the cells undergo senescence and cell death. A study was conducted to investigate the role of telomerase, an RNA-containing enzyme that restores the telomere length, in the neoplastic cell immortalization and progression process. Fresh human tissue samples taken from excision specimens received by the Department of Pathology, University of Malaya Medical Centre, were investigated for telomerase activity using a commercial Telomerase PCR-ELISA kit (Boehringer Mannheim). Specimens comprised 33 breast lesions (10 infiltrating breast adenocarcinoma, 13 fibroadenoma and 10 non-neoplastic breast tissue), 27 colonic lesions (17 colonic adenocarcinoma and 10 non-neoplastic colonic mucosa) and 42 cervical lesions (20 cervical carcinoma and 22 non-neoplastic cervical tissues). Telomerase activity was found in 6 (60%) of 10 breast carcinomas, 6 (46%) of 13 fibroadenomas, none of the 10 nonneoplastic breast samples, 3 (17.6%) of 17 colon carcinomas and none of the 10 non-neoplastic colonic mucosal samples, 12 (60%) of 20 cervical carcinoma and 3 (13.6%) of 22 non-neoplastic cervical samples. 5/10 (50%) Stage I, 4/7 (57%) Stage II, 2/2 (100%) Stage III and 1/1 (100%) Stage IV cervical carcinomas showed telomerase activity. These findings support a contributory role for telomerase in tumourigenesis with activation occurring from neoplastic transformation and increasing with tumour progression.
  18. Cheah PL, Kunaseegaran R, Looi LM
    Malays J Pathol, 2001 Jun;23(1):27-30.
    PMID: 16329544
    Ki-67 expression in diffuse proliferative lupus nephritis, WHO Class IV, was compared against normal controls to establish that cellular proliferation is involved in the production of glomerular hypercellularity. Twenty-three histologically confirmed WHO Class IV lupus nephritis and 23 normal control renal tissue were immunohistochemically stained with a polyclonal antibody to Ki-67 (Dako) using the peroxidase labelled streptavidin bioitin kit (Dako). There were 20 females and 3 males, with 17 Chinese and 6 Malays in the WHO Class IV lupus nephritis group. Ages of patients ranged between 10-56 years with a mean of 31.9 years. The normal controls, 20 males and 3 females, and ethnically 9 Indians, 7 Malays, 2 Chinese, and 5 foreign nationals (4 Indonesians and 1 Bangladeshi), had an age range between 15-33 years (mean = 23.3 years). Sixteen (69.6%) WHO Class IV lupus nephritis and 8 (34.8%) normal controls demonstrated Ki-67 immunoreactivity in at least 1 glomerulus (p<0.05). Of the 256 WHO Class IV lupus nephritis non-sclerosed, glomeruli studied, 37 (14.5%) were Ki-67 immunopositive compared with normal controls where 16 (0.7%) of 2159 glomeruli demonstrated Ki-67 (p< 0.01). Cellular proliferative activity, as evidenced by Ki-67 expression, was significantly increased in WHO Class IV lupus nephritis confirming that cell proliferation contributes to glomerular hypercellularity.
  19. Amalourde A, Vinayaga P, Naveed N, Jamal A, Looi LM, Sengupta S
    Med J Malaysia, 2004 Dec;59 Suppl F:60-2.
    PMID: 15941166 MyJurnal
    Although all types of tumour and tumour-like conditions have been described to occur in the clavicle, they only contribute to less then 0.5% of all skeletal tumours. The incidence of primary chondrosarcoma of the clavicle is extremely rare. To our knowledge it has not been reported in Malaysia. We would like to highlight the possibility of chondrosarcoma as a differential diagnosis for a clavicular lesion.
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