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Biomedical subjects

L M Looi

Publications and source records attributed to L M Looi.

At least 55 records · Page 3Linked to original sources

Correlation between oestrogen receptor protein expression in infiltrating ductal carcinoma of the breast by immunohistochemistry and cytosol measurements.

Fresh frozen neoplastic tissues from 70 infiltrating ductal breast carcinomas were analysed for cytosolic oestrogen receptor (ER) protein content using a solid phase enzyme immunoassay (EIA) method based on a "sandwich" principle (Abbott ER-EIA monoclonal). Formalin-fixed, paraffin-embedded sections from the same carcinomas were examined for nuclear immunoreactivity against a monoclonal antibody for ER protein (Dako) using the standard avidin-biotin complex immunoperoxidase (IP) method after microwave antigen retrieval. The degree of ER positivity by IP was also scored according to a visual estimation of the percentage of cells expressing immunopositivity and the intensity of staining. Twenty-eight (40%) of the carcinomas were ER-positive by EIA and 34 (48.6%) were positive by IP. Twenty-five (35.7%) were ER-positive and 33 (47.1%) were ER-negative by both methods. Nine (12.9%) were ER-negative by EIA but were positive by IP, this discrepancy being ascribed to sampling inadequacy for EIA. However, 3 (4.3%) tumours were ER-positive by EIA and negative by IP. This discrepancy may be variously due to inadequate antigen retrieval, faulty technique and the possibility that the two methods do not measure identical ER proteins. IP appears to have an advantage over EIA in that it has a higher pick-up rate, does not require fresh tissue and can be applied to archival material. However, to reduce false negative estimations, it may be necessary to run IP staining using more than one ER antibody. Standardisation of the IP method for ER is desirable before this method is to be widely adopted in Malaysian laboratories. Quantitation of ER positivity by IP scoring correlated poorly with actual cytosolic levels. Caution should be exercised in attaching patient management value to visual IP scoring.

Breast Neoplasms↗

Immunohistochemical expression of p53 proteins in Wilms' tumour: a possible association with the histological prognostic parameter of anaplasia.

Wilms' tumour (nephroblastoma) has been associated with chromosomal abnormalities at the 11p13, 11p15 and 16q regions. A study into the possibility of mutations occurring within p53, the ubiquitous adult tumour suppressor gene, in Wilms' tumour was carried out. Thirty-eight cases were studied. Of these 36 were categorised into the favourable histology group and two into the unfavourable histology group based on the National Wilms' Tumour Study criteria. Archival formalin-fixed, paraffin-embedded tissue sections from each case were stained with a polyclonal (AB565:Chemicon) and a monoclonal (DO7:Dako) antibody raised against p53 protein using a peroxidase-labelled streptavidin biotin kit (Dako). 'Cure' (disease-free survival of 60 months or longer) was documented in 39% of cases with favourable histology tumours. Eleven percent in this group succumbed to the disease. Both cases with unfavourable histology died. Four out of 36 (11%) tumours with favourable histology demonstrated weak to moderate staining with both AB565 and DO7 in more than 75% of tumour cells. In contrast, p53 protein expression in unfavourable histology tumours was significantly increased compared with the favourable histology group (P = 0.021) with both cases demonstrating immunopositivity in > 75% of tumour cells when stained with AB565 and DO7. The intensity of staining ranged from moderate to strong in both cases. It appears from this preliminary study that the immunohistochemical expression of p53 protein in Wilms' tumour, presumably a result of mutation in the p53 tumour suppressor gene, correlates with histological classification, histological categorisation being one of the useful features in the prognostic assessment of Wilms' tumours.

Anaplasia↗

Implications of p53 protein expression in clear cell sarcoma of the kidney.

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.

Child, Preschool↗

Problems in the histological assessment of hydatidiform moles: a study on consensus diagnosis and ploidy status by fluorescent in situ hybridisation.

Hydropic villi in products of conception continue to pose a diagnostic problem for the anatomical pathologist. It is important to distinguish between complete hydatidiform mole (CM), partial hydatidiform mole (PM) and hydropic degeneration (HD), as hydatidiform moles (especially CM) have a tendency to develop persistent trophoblastic disease. Several studies have demonstrated interobserver variability in the diagnosis of the three conditions, but there have been no studies testing the accuracy of the consensus diagnosis of pathologists experienced in the field. In this study four anatomical pathologists with experience in diagnosing hydatidiform moles selected five cases of HD, seven cases of PM and ten cases of CM on the basis of consensus diagnosis using established criteria. Ploidy studies were done on these 22 cases using fluorescent in situ hybridisation. The 15 cases of HD and CM were diploid, confirming the histological diagnosis. However only five of the seven cases of PM were triploid, the other two being diploid. Review of these two diploid cases showed a mixture of small and large villi with moderate to marked trophoblastic proliferation. On the basis of the significant trophoblastic proliferation and the DNA information, the two cases were reclassified as early complete moles. This study demonstrates that even pathologists experienced in the field have difficulty separating PM from CM. The findings suggest that, in the absence of DNA information, a lesion with hydropic villi showing moderate to marked trophoblastic proliferation should be classified as a complete mole, even if there is a mixture of small and large villi. Ploidy studies are an important adjunct to histological diagnosis, especially when there is an overlap of features.

Diagnosis, Differential↗

Microcalcification clustering parameters in breast disease: a morphometric analysis of radiographs of excision specimens.

X-ray microradiography of surgically excised breast specimens offers the possibility of morphological characterization of calcifications. When combined with digital imaging techniques there exists added potential for obtaining valuable basic quantitative morphometric information regarding differences between microcalcifications in tissues exhibiting evidence of fibrocystic change, benign and malignant tumours. A total of 157 excised breast specimens from 84 patients were microradiographed using a Softex Super Soft X-ray unit and Kodak AA high resolution industrial film. A Quantimet 570C image analysis system was used to digitize and analyse the microradiographs. Of the 157 microradiographs, 51 (from 30 patients) revealed microcalcification clusters. The existence of significant differences between the three identified categories of tissue were indicated by clustering parameters. These included the number of particles per cluster, area of clusters, maximum distance to nearest neighbour, and geometric mean distance to nearest neighbour. The distribution pattern index (DPI), another of the clustering parameters used in this study, has been observed to be a particularly powerful discriminator. The value for fibrocystic change was found to be significantly smaller (0.514) than that for benign tumour (0.796) whilst that for benign tumour was observed to be significantly larger than that for malignant tumour (0.604) at a p-value of less than 0.05 (Kruskal-Wallis one-way analysis of variance).

Adolescent↗

Cutaneous adnexal neoplasms in biopsy specimens processed in the Department of Pathology, University of Malaya.

A review of consecutive biopsies of adnexal tumours from 112 patients, received by the Department of Pathology, University of Malaya, over a 13-year period was undertaken. The age range of the patients was from 1 to 84 years, with a mean of 29.8 years. Thirty-three (32%) patients were under 20 years of age. There were 68 females with a male to female ratio of 1.0:1.5. In 105 cases (93.7%), the neoplasm was solitary. The tumour measured less than 2 cm in the largest dimension in 103 cases (92%). The common sites of occurrence were the head and neck region (59%) and extremities (25%). Neoplasms of hair follicle origin accounted for 63.4% (71 cases) of all lesions. Intra-tumour deposition of amyloid was noted in one of the 14 cases of trichoepithelioma.

Adolescent↗

Fibrillary deposits: amyloids and tactoids.

Two forms of abnormal fibrillary protein deposition are considered: amyloidosis and fibrillary (immunotactoid) glomerulonephritis. Amyloid is characterised by an antiparallel, beta-pleated configuration which imparts to it a unique apple-green birefringence after Congo red staining. Inspite of its fairly constant physical properties, the chemical composition of amyloid fibrils is amazingly diverse, encomposing AA protein, light chain fragments, transthyretin, procalcitonin, islet amyloid polypeptide, atrial natriuretic peptides, beta-amyloid protein, beta-2-microglobulin, cystatin C, gelsolin, apolipoprotein A1, lyzozyme and their mutant variants. Amyloid P component and heparan sulphate proteoglycan are ubiquitous non-fibrillary amyloid components which have significant roles in the amyloidogenetic process, as do also precursor fibril proteins. Different amyloid fibril proteins relate to different amyloidosis syndromes and different histological patterns, and provide the basis for new diagnostic approaches to this disorder. Glomerular deposits in fibrillary glomerulonephritis (FGN), although often mistaken for amyloid, differ from it in its negative Congophilia, wider fibril width and highly organised, microtubular-tactoidal appearance ultrastructurally. FGN is essentially a primary glomerulopathy resulting in progressive renal failure. Despite certain differences, intriguing similarities between both entities of fibrillary deposition pose a challenge to researchers as to the mechanisms of abnormal protein crystallization and fibril formation in tissues.

Adult↗

Expression of placental proteins in complete and partial hydatidiform moles.

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.

Adult↗

Squamous cell carcinoma antigen as an adjunct tumour marker in primary carcinoma of the lung.

AIMS: To determine (1) the detection rate of primary carcinoma of the lung by serological assay of CEA (carcinoembryonic antigen); and (2) whether addition of seroassay of squamous cell carcinoma related antigen before treatment improves detection sensitivity. METHODS: A prospective study spanning 27 months was conducted at the University Hospital, Kuala Lumpur. Serum CEA (Abbott IMx) and serum squamous cell carcinoma antigen (Abbott IMx) from patients clinically suspected of having primary carcinoma of the lung, were assayed using the microparticle enzyme immunoassay method. RESULTS: Thirty seven cases of histologically confirmed primary lung carcinoma were studied. Of these, 17 were squamous cell carcinomas, 10 adenocarcinomas, nine small cell carcinomas, and one large cell carcinoma. The patients' ages ranged from 34-82 years. The male:female ratio was 3.6:1. Squamous cell carcinoma antigen was raised above the cutoff value of 1.5 ng/ml in 94.1% of squamous cell carcinomas, 20.0% of adenocarcinomas, and 11.1% of small cell carcinomas. By comparison, CEA was raised above the cutoff value of 3.0 ng/ml in 70.6% of squamous cell carcinomas, 77.8% of small cell carcinomas, and 100% of adenocarcinomas. CEA and squamous cell carcinoma antigen were not raised in the patient with large cell carcinoma and in 14 healthy volunteers. None of 15 patients with a variety of benign lung diseases showed a rise of CEA, while two patients--a 25 year old Indian woman with pneumonia and a 64 year old Malay man with bronchial asthma--had raised squamous cell carcinoma antigen values above the cutoff. Serum CEA and squamous cell carcinoma antigen values did not seem to correlate with stage or degree of differentiation of the tumours. CONCLUSIONS: The findings suggest that CEA is a good general marker for carcinoma, particularly adenocarcinoma. In contrast, squamous cell carcinoma antigen is more specific for squamous carcinoma.

Adenocarcinoma↗

The pattern of amyloidosis in Malaysia.

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.

Adolescent↗

The pattern of renal disease in Malaysia.

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.

Adolescent↗

Malignant rhabdoid tumour of the kidney: report of a case showing focal glomeruloid differentiation.

A five-month-old male baby presented with an abdominal mass which was found on computerised tomography (CT) to be involving the left kidney. Nephrectomy and histopathological study showed morphological featues of a malignant rhabdoid tumour. The tumour cells stained strongly for cytokeratin and epithelial membrane antigen and less intensely for vimentin. Electron microscopy revealed concentric whorled arrays of intermediate filaments within the tumour cell cytoplasm. The child was put on post-operative chemotherapy and radiotherapy but developed bilateral lung metastases and died three months after surgery.

Biomarkers, Tumor↗

Isolated atrial amyloidosis: a clinicopathologic study indicating increased prevalence in chronic heart disease.

Congo red screening of 211 consecutive cardiac biopsy specimens obtained during cardiac surgery from 167 patients revealed 26 (16%) instances of isolated atrial amyloidosis (IAA). The ages of IAA-positive patients ranged from 25 to 52 years (mean age, 39 years). Twenty-three (88%) IAA-positive biopsy specimens were from patients with chronic rheumatic heart disease (CRHD) while three (12%) were from patients with an atrial septal defect (ASD). The prevalence of IAA in the CRHD patients was 23%, appreciably higher than that in the ASD patients (15%) and in other patients with atrial biopsies. The prevalence of IAA in both CRHD and ASD patients was significantly higher (P < .001) than in controls. Controls consisted of 247 healthy adults who were autopsied after traumatic deaths, with an age range of 18 to 89 years (mean age, 38 years). Only seven (3%) control subjects were IAA positive; all were over 40 years of age. Isolated atrial amyloidosis deposits were permanganate resistant and immunohistochemically positive for human amyloid P (AP) protein and negative for human amyloid-associated (AA) protein and immunoglobulin light chains. They were observed as fine congophilic and birefringent deposits in intramyocardial vessel walls, along the myocardial sarcolemma, and in the subendocardium. There was associated myocyte hypertrophy but no atrophy. Electron microscopy demonstrated typical nonbranching amyloid fibrils. It is postulated that stretching of the atria in chronic heart disease results in a raised prevalence of IAA. Recent reports that IAA contains atrial natriuretic peptide, a polypeptide hormone product of atrial myocytes, supports this view.

Adolescent↗

Differentiation of elemental composition of normal and malignant breast tissue by instrumental neutron activation analysis.

Multi-elemental quantitative analyses of 15 paired samples of normal and malignant human breast tissue by instrumental neutron activation analysis are reported. The elements, Al, Br, Ca, Cl, Co, Cs, Fe, K, Na, Rb, Zn were detected. Significantly elevated concentration levels were found for Al, Br, Ca, Cl, Cs, K, Na, Zn in malignant compared to normal tissue. Although the role of elemental composition in breast cancer is unclear, this finding may be of importance as another parameter for differentiating normal from malignant tissue.

Breast↗

Aggressive angiomyxoma of the vulva with an unusual vascular finding.

We report the first documented Malaysian case of aggressive angiomyxoma (AAM) of the vulva. A 56-yr-old woman of Indian ethnic origin presented with a vulval lesion which was clinically mistaken for a Bartholin's cyst. The lesion was surgically excised and a diagnosis of AAM was made histologically. Of particular interest was the finding of foamy and mononuclear inflammatory cells and fibrin in the walls of most of the lesional blood vessels. The patient recovered uneventfully and remains without tumor recurrence at the time of writing 37 mths after initial presentation.

Female↗