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

Ng KH, Bradley DA, Looi LM, Mahmood CS, Wood AK

Appl Radiat Isot, 1993 Mar;44(3):511-6.
PMID: 8472024

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.
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.
Aberrant expression of acute-phase reactant proteins in sera and breast lesions of patients with malignant and benign breast tumors

Doustjalali SR, Yusof R, Yip CH, Looi LM, Pillay B, Hashim OH

Electrophoresis, 2004 Jul;25(14):2392-401.
PMID: 15274022

We have analyzed unfractionated sera of newly diagnosed patients (n=10) with breast carcinoma (BC), prior to treatment, and patients (n=5) with fibrocystic disease of the breast (FDB) by two-dimensional gel electrophoresis (2-DE) and silver staining. The patients' 2-DE serum protein profiles obtained were then subjected to image analysis and compared to similar data generated from sera of normal healthy female controls (n=10) of the same range of age. The relative expression of alpha1-antichymotrypsin (ACT), clusterin, and complement factor B was significantly higher in all BC patients as compared to normal controls. However, the expression of alpha1-antitrypsin (AAT) in BC patients was apparently lower than that of the controls. Similar differential expression of ACT was detected in the FDB patients. The aberrant expression of the serum acute-phase proteins of patients with BC and FDB was confirmed by competitive enzyme-linked immunosorbent assay (ELISA). Similar altered proteins expression was also observed from immunohistochemical studies of malignant (n=5) and benign (n=5) breast lesions of the respective patients performed using antisera to the aberrantly expressed proteins. However, the malignant breast lesions were instead positively stained for AAT. The differential expression of the serum proteins was apparently abrogated when a six-month follow-up study was performed on nine of the BC patients subsequent to treatment.
Effect of soy protein on the small bowel mucosa of young infants recovering from acute gastroenteritis

Iyngkaran N, Yadav M, Looi LM, Boey CG, Lam KL, Balabaskaran S, et al.

J Pediatr Gastroenterol Nutr, 1988 Jan-Feb;7(1):68-75.
PMID: 3335989

The effect of soy protein on the small bowel mucosa of 18 infants with acute gastroenteritis was studied. The infants were maintained on a protein hydrolysate formula for 6-8 weeks, following which they were readmitted for soy protein challenge studies. Jejunal biopsy was performed before and 24 h after challenge. On the basis of the clinical and histological reaction to soy protein challenge, three groups were identified. Group 1 consisted of three infants who had clinical and histological reaction. There was associated depletion of mucosal enzymes, lactase, sucrase, malatase, alkaline phosphatase, and blood xylose levels. Group 2 consisted of seven infants who had histological reaction but no clinical symptoms. Two of these seven infants, however, developed clinical reaction when rechallenged with soy protein 2 and 90 days later. Following challenge, mucosal enzymes and blood xylose levels were depressed in five of the seven infants tested. Group 3 consisted of eight infants who did not have either a clinical or a histological reaction. The mucosal enzymes and blood xylose levels were not depressed in four infants tested. The present study shows that the small bowel mucosa of some young infants recovering from acute gastroenteritis remains sensitive to soy protein for a variable period of time. The feeding of soy protein to these infants may result in the persistence of mucosal damage and perpetuation of diarrhea.(ABSTRACT TRUNCATED AT 250 WORDS)
Breast cancer hormone receptor testing in Asia: is it time to think again on expected positivity rates and methods of scoring?

Rhodes A, Teoh KH, See MH, Ganesan K, Looi LM

Pathology, 2020 Apr;52(3):385-387.
PMID: 32107079 DOI: 10.1016/j.pathol.2019.12.006
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.
Fulltext DNA mismatch repair and CD133-marked cancer stem cells in colorectal carcinoma

Cheah PL, Li J, Looi LM, Teoh KH, Ong DB, Arends MJ

PeerJ, 2018;6:e5530.
PMID: 30221090 DOI: 10.7717/peerj.5530

Background: Except for a few studies with contradictory observations, information is lacking on the possibility of association between DNA mismatch repair (MMR) status and the presence of cancer stem cells in colorectal carcinoma (CRC), two important aspects in colorectal carcinogenesis.
Methods: Eighty (40 right-sided and 40 left-sided) formalin-fixed, paraffin-embedded primary CRC were immunohistochemically studied for CD133, a putative CRC stem cell marker, and MMR proteins MLH1, MSH2, MSH6 and PMS2. CD133 expression was semi-quantitated for proportion of tumor immunopositivity on a scale of 0-5 and staining intensity on a scale of 0-3 with a final score (units) being the product of proportion and intensity of tumor staining. The tumor was considered immunopositive only when the tumor demonstrated moderate to strong intensity of CD133 staining (a decision made after analysis of CD133 expression in normal colon). Deficient MMR (dMMR) was interpreted as unequivocal loss of tumor nuclear staining for any MMR protein despite immunoreactivity in the internal positive controls.
Results: CD133 was expressed in 36 (90.0%) left-sided and 28 (70.0%) right-sided tumors (p 0.05).
Conclusion: Proficient MMR correlated with high levels of CD133-marked putative cancer stem cells in both right- and left-sided tumors, whereas significantly lower levels of CD133-marked putative cancer stem cells were associated with deficient MMR status in colorectal carcinomas found on the right.
A review on omics-based biomarkers discovery for Alzheimer's disease from the bioinformatics perspectives: Statistical approach vs machine learning approach

Tan MS, Cheah PL, Chin AV, Looi LM, Chang SW

Comput Biol Med, 2021 12;139:104947.
PMID: 34678481 DOI: 10.1016/j.compbiomed.2021.104947

Alzheimer's Disease (AD) is a neurodegenerative disease that affects cognition and is the most common cause of dementia in the elderly. As the number of elderly individuals increases globally, the incidence and prevalence of AD are expected to increase. At present, AD is diagnosed clinically, according to accepted criteria. The essential elements in the diagnosis of AD include a patients history, a physical examination and neuropsychological testing, in addition to appropriate investigations such as neuroimaging. The omics-based approach is an emerging field of study that may not only aid in the diagnosis of AD but also facilitate the exploration of factors that influence the development of the disease. Omics techniques, including genomics, transcriptomics, proteomics and metabolomics, may reveal the pathways that lead to neuronal death and identify biomolecular markers associated with AD. This will further facilitate an understanding of AD neuropathology. In this review, omics-based approaches that were implemented in studies on AD were assessed from a bioinformatics perspective. Current state-of-the-art statistical and machine learning approaches used in the single omics analysis of AD were compared based on correlations of variants, differential expression, functional analysis and network analysis. This was followed by a review of the approaches used in the integration and analysis of multi-omics of AD. The strengths and limitations of multi-omics analysis methods were explored and the issues and challenges associated with omics studies of AD were highlighted. Lastly, future studies in this area of research were justified.
ERRATUM: Phyllodes tumours of the breast: retrospective analysis of a University Hospital's experience

Toh YF, Cheah PL, Looi LM, Teoh KH, Tan PH

Malays J Pathol, 2016 08;38(2):175.
PMID: 27568677

No abstract available.
Cyclooxygenase-2 (COX2) expression in adenocarcinoma surpasses that of squamous cell carcinoma in the uterine cervix

Marutha Muthu AK, Cheah PL, Koh CC, Chew MF, Toh YF, Looi LM

Malays J Pathol, 2017 Dec;39(3):251-255.
PMID: 29279587 MyJurnal

Over the years, adenocarcinoma (ADC), which has a worse prognosis than squamous cell carcinoma (SCC) of the cervix, has shown an increasing trend. Cyclooxygenase-2 (COX2) expression which has been associated with worse prognosis in several solid cancers was studied for its association with SCC and ADC of the cervix. 35 histologically re-confirmed SCC and 35 ADC were immunohistochemically stained for COX2 using a mouse monoclonal antibody to COX2 (1:100; Dako: Clone CX-294) on a Ventana Benchmark XT. The histoscore was computed as intensity of staining, semi-quantitated on a scale of 0-3 with 0 = negative, 1 = weak, 2 = moderate and 3 = strong staining intensity; multiplied by percentage of immunopositivity on a scale of 0-4 with 0 = <1%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75% and 4 = ≥75% of immunopositive tumour cells. Histoscore 1-3/12 was considered as low and ≥4/12 as high COX2 expression. SCC affected Chinese more than Malays, while Malays had more ADC (p = 0.032). Mean age at presentation of SCC (57.5 years) was about a decade later than ADC at 47.9 years (p = 0.002). 30/35 (85.7%) of SCC and 34/35 (97.1%) of ADC expressed COX2. Histoscores of ADC (median = 4.0, IQR = 3.0-6.0) was significantly higher (p = 0.014) than those of SCC (median = 3.0, IQR = 2.0-3.0). High histoscores (≥4/12) were more frequent in ADC (55.9%) compared with SCC (26.7%) (p = 0.018), implicating COX2, either directly or indirectly, as a possible player in influencing the poorer outcome of ADC compared with SCC.
Delivering modern, high-quality, affordable pathology and laboratory medicine to low-income and middle-income countries: a call to action

Horton S, Sullivan R, Flanigan J, Fleming KA, Kuti MA, Looi LM, et al.

Lancet, 2018 05 12;391(10133):1953-1964.
PMID: 29550030 DOI: 10.1016/S0140-6736(18)30460-4

Modern, affordable pathology and laboratory medicine (PALM) systems are essential to achieve the 2030 Sustainable Development Goals for health in low-income and middle-income countries (LMICs). In this last in a Series of three papers about PALM in LMICs, we discuss the policy environment and emphasise three crucial high-level actions that are needed to deliver universal health coverage. First, nations need national strategic laboratory plans; second, these plans require adequate financing for implementation; and last, pathologists themselves need to take on leadership roles to advocate for the centrality of PALM to achieve the Sustainable Development Goals for health. The national strategic laboratory plan should deliver a tiered, networked laboratory system as a central element. Appropriate financing should be provided, at a level of at least 4% of health expenditure. Financing of new technologies such as molecular diagnostics is challenging for LMICs, even though many of these tests are cost-effective. Point-of-care testing can substantially reduce test-reporting time, but this benefit must be balanced with higher costs. Our research analysis highlights a considerable deficiency in advocacy for PALM; pathologists have been invisible in national and international health discourse and leadership. Embedding PALM in LMICs can only be achieved if pathologists advocate for these services, and undertake leadership roles, both nationally and internationally. We articulate eight key recommendations to address the current barriers identified in this Series and issue a call to action for all stakeholders to come together in a global alliance to ensure the effective provision of PALM services in resource-limited settings.
Access to pathology and laboratory medicine services: a crucial gap

Wilson ML, Fleming KA, Kuti MA, Looi LM, Lago N, Ru K

Lancet, 2018 05 12;391(10133):1927-1938.
PMID: 29550029 DOI: 10.1016/S0140-6736(18)30458-6

As global efforts accelerate to implement the Sustainable Development Goals and, in particular, universal health coverage, access to high-quality and timely pathology and laboratory medicine (PALM) services will be needed to support health-care systems that are tasked with achieving these goals. This access will be most challenging to achieve in low-income and middle-income countries (LMICs), which have a disproportionately large share of the global burden of disease but a disproportionately low share of global health-care resources, particularly PALM services. In this first in a Series of three papers on PALM in LMICs, we describe the crucial and central roles of PALM services in the accurate diagnosis and detection of disease, informing prognosis and guiding treatment, contributing to disease screening, public health surveillance and disease registries, and supporting medical-legal systems. We also describe how, even though data are sparse, these services are of both insufficient scope and inadequate quality to play their key role in health-care systems in LMICs. Lastly, we identify four key barriers to the provision of optimal PALM services in resource-limited settings: insufficient human resources or workforce capacity, inadequate education and training, inadequate infrastructure, and insufficient quality, standards, and accreditation.
Fulltext Indication of high lipid content in epithelial-mesenchymal transitions of breast tissues

Sabtu SN, Sani SFA, Looi LM, Chiew SF, Pathmanathan D, Bradley DA, et al.

Sci Rep, 2021 Feb 05;11(1):3250.
PMID: 33547362 DOI: 10.1038/s41598-021-81426-x

The epithelial-mesenchymal transition (EMT) is a crucial process in cancer progression and metastasis. Study of metabolic changes during the EMT process is important in seeking to understand the biochemical changes associated with cancer progression, not least in scoping for therapeutic strategies aimed at targeting EMT. Due to the potential for high sensitivity and specificity, Raman spectroscopy was used here to study the metabolic changes associated with EMT in human breast cancer tissue. For Raman spectroscopy measurements, tissue from 23 patients were collected, comprising non-lesional, EMT and non-EMT formalin-fixed and paraffin embedded breast cancer samples. Analysis was made in the fingerprint Raman spectra region (600-1800 cm-1) best associated with cancer progression biochemical changes in lipid, protein and nucleic acids. The ANOVA test followed by the Tukey's multiple comparisons test were conducted to see if there existed differences between non-lesional, EMT and non-EMT breast tissue for Raman spectroscopy measurements. Results revealed that significant differences were evident in terms of intensity between the non-lesional and EMT samples, as well as the EMT and non-EMT samples. Multivariate analysis involving independent component analysis, Principal component analysis and non-negative least square were used to analyse the Raman spectra data. The results show significant differences between EMT and non-EMT cancers in lipid, protein, and nucleic acids. This study demonstrated the capability of Raman spectroscopy supported by multivariate analysis in analysing metabolic changes in EMT breast cancer tissue.
Epithelial-mesenchymal transition profiles in triple negative breast carcinoma may explain its aggressive nature

Chiew SF, Looi LM, Cheah PL, Teoh KH, Chang SW, Abdul Sani SF

Malays J Pathol, 2023 Dec;45(3):363-374.
PMID: 38155378

Epithelial-mesenchymal transition (EMT) is increasingly explored in cancer progression. Considering that triple negative (TN) breast cancer has the poorest survival among molecular subtypes, we investigated 49 TN, 45 luminal and 25 HER2-enriched female breast carcinomas for EMT expression (using E-cadherin and vimentin immunohistochemistry) against lymphovascular and/or lymph node invasion. E-cadherin and vimentin expressions were semi-quantitated for positive- cancer cells (0=0-<1%, 1=1-10%, 2 =11-50%, 3=>50%) and staining intensity (0=negative, 1=weak, 2=moderate, 3=strong), with final score (low=0-4 and high=6-9) derived by multiplying percentage and intensity scores for each marker. Low E-cadherin and/or high vimentin scores defined EMT positivity. Low E-cadherin co-existing with high vimentin defined "complete" (EMT-CV), while low E-cadherin (EMT-C) or high vimentin (EMT-V) occurring independently defined "partial" subsets. 38 (31.9%) cancers expressed EMT, while 59.2 % TN, 13.3% luminal and 12% HER2-enriched cancers expressed EMT (p<0.05). Among the cancers with lymphovascular and/or lymph node invasion, EMT positivity by molecular types were 66.7% TN, 7.4% luminal and 11.8% HER2-enriched (p<0.05). Although EMT-V, associated with stem-cell properties was the dominant TN EMT profile, EMT-CV, a profile linked to vascular metastases, was encountered only in TN. EMT appears important in TN cancer and different EMT profiles may be associated with its aggressive nature.
Fulltext Superficial acral fibromyxoma: insights from case management and comprehensive literature review

Tan HL, Ahmad TS, Sankara Kumar C, Khirusman Adnan Y, Looi LM, Gunasagaran J

EFORT Open Rev, 2024 Feb 01;9(2):129-137.
PMID: 38306799 DOI: 10.1530/EOR-23-0151

Superficial acral fibromyxoma, also known as digital fibromyxoma, is a slow-growing, benign, solitary soft tissue tumor. First described in 2001 by Fetsch et al., it is a condition that often occurs in middle-aged individuals. However, it has also been reported across a wide range of ages, ranging from 4 to 86 years, with males more commonly reported. The condition often presents as solitary soft tissue swelling over the periungual or subungual. We present the management experience of the rare presentation of this rare tumor and a detailed review of the past literature on this condition. Detailed management of the condition has been described, along with the outcome after 2 years of follow-up and treatment experience. Our detailed analysis shows that 2 years is the shortest duration of follow-up to rule out recurrence. Hence, most of the cases reported earlier had given the false sense of the recurrence rate of the tumor, which could lead to undertreatment of the condition. The purpose of this article is to allow the readers to understand better the tumor's characteristics with bone involvement and the tumor's diagnostic strategies and treatment options.
Do clinical features and survival of single hormone receptor positive breast cancers differ from double hormone receptor positive breast cancers?

Ng CH, Pathy NB, Taib NA, Ho GF, Mun KS, Rhodes A, et al.

Asian Pac J Cancer Prev, 2014;15(18):7959-64.
PMID: 25292095

The significance of the single hormone receptor positive phenotype of breast cancer is still poorly understood. The use of hormone therapy has been found to be less effective for this type, which has a survival outcome midway between double positive and double negative phenotypes. The aim of this study was to investigate differences in patient and tumor characteristics and survival between double-receptor positive (ER+PR+), double receptor negative (ER-PR-) and single receptor positive (ER+PR- and ER-PR+) breast cancer in an Asian setting. A total of 1,992 patients with newly diagnosed stage I to IV breast cancer between 2003 and 2008, and where information on ER and PR were available, were included in this study. The majority of patients had ER+PR+ tumors (n=903: 45.3%), followed by 741 (37.2%) ER-PR-, 247 (12.4%) ER+PR-, and 101 (5.1%) ER-PR+ tumors. Using multivariate analysis, ER+PR- tumors were 2.4 times more likely to be grade 3 compared to ER+PR+ tumors. ER+PR- and ER-PR+ tumors were 82% and 86% respectively less likely to be grade 3 compared with ER-PR- tumors. ER-PR+ tumours were associated with younger age. There were no survival differences between patients with ER+PR+ and ER-PR+ tumors. However, ER+PR- tumors have poorer survival compared with ER+PR+ tumours. ER-PR- tumours had the worst survival. Adjuvant hormonal therapy with tamoxifen was found to have identical survival advantage in patients with ER+PR+ and ER-PR+ tumors whereas impact was slightly lower in patients with ER+PR- tumors. In conclusion, we found ER+PR- tumors to be more aggressive and have poorer survival when compared to ER+PR+ tumors, while patients with ER-PR+ tumours were younger, but had a similar survival to their counterparts with ER+PR+ tumours.
Clinical predictors of non-diabetic renal disease and role of renal biopsy in diabetic patients with renal involvement: a single centre review

Chong YB, Keng TC, Tan LP, Ng KP, Kong WY, Wong CM, et al.

Ren Fail, 2012;34(3):323-8.
PMID: 22250665 DOI: 10.3109/0886022X.2011.647302

BACKGROUND:
Type 2 diabetes mellitus (T2DM) is reportedly the leading cause of end-stage renal disease (ESRD) worldwide. However, non-diabetic renal diseases (NDRD) are not uncommon among T2DM patients with renal involvement. Our study aimed to examine the prevalence of NDRD in T2DM and clinical markers for diabetic nephropathy (DN) and NDRD and to determine the role of renal biopsy in T2DM patients and its impact on clinical practice.

METHODS:
We conducted a retrospective analysis of T2DM patients in whom renal biopsies were performed from January 2004 to March 2008 (n = 110).

RESULTS:
Biopsy results were divided into three groups: group I/pure DN (62.7%), group II/isolated NDRD (18.2%), and group III/mixed lesions (19.1%). The causes of NDRD in decreasing order of frequency were acute interstitial nephritis, glomerulonephritides, hypertensive renal disease, and acute tubular necrosis. Significant clinical markers for DN are presence of diabetic retinopathy and longer duration of diabetes. For NDRD, useful clinical markers include the presence of acute renal failure and microscopic hematuria. In the DN subgroup, Indians had significantly shorter duration of diabetes on biopsy compared with Malays and Chinese.

CONCLUSIONS:
NDRD is prevalent in T2DM patients, and given its potentially treatable nature, renal biopsy should be considered in T2DM patients with nephropathy, especially in those with atypical features.
Fulltext Deaths in children during an outbreak of hand, foot and mouth disease in Peninsular Malaysia--clinical and pathological characteristics

Shekhar K, Lye MS, Norlijah O, Ong F, Looi LM, Khuzaiah R, et al.

Med J Malaysia, 2005 Aug;60(3):297-304.
PMID: 16379183

From July through December 1997, 11 previously healthy children in Peninsular Malaysia succumbed to an illness clinically characterised by an acute severe refractory left-ventricular failure, following a brief prodromal illness, in the midst of an outbreak of hand, foot and mouth disease (HFMD), similar to the reported experience in Sarawak and Taiwan. Retrospective reviews of the clinical features and results of laboratory, pathological and virological investigations of cases were conducted. The median age of the 11 case-patients was 31 months (range, 13 to 49 months); 6 were males. A brief prodromal illness of 3 days (range, 2 to 5 days) was characterised by fever (axillary temperature > 38 degrees C) (100%), oral ulcers (72%), extremity rashes (45%) and significant vomiting (55%). Upon hospitalisation, 7 of 11 case-patients had features suggestive of cardiogenic shock, while 4 of 11 case-patients developed shock during hospitalisation as evidenced by marked sustained tachycardia (heart rate > or = 180 beats per minute), poor peripheral pulses and peripheral perfusion, mottled extremities, pulmonary oedema (haemorrhagic pulmonary secretions in 8 of 11 cases during tracheal intubation, often precipitated by conservative crystalloid boluses, and radiographic evidence of acute pulmonary oedema in 5 of 7 cases) and markedly impaired left ventricular function on echocardiographic examination (7 of 7 cases). Three of 4 case-patients had aseptic meningitis while one case-patient also had an acute flaccid paraparesis. Despite supportive therapy, death occurred within a median of 13.4 hours following hospitalization. Post-mortem findings (all 8 specimens examined) consistently demonstrated brain-stem encephalitis with foci of neuronal necrosis and micro-abscesses. None of the 11 specimens examined revealed histological evidence of myocarditis. Enterovirus 71 (EV71) was detected in 10 of 11 case-patients, many (7) from various sterile tissue sites (5 from central nervous tissues). No other viruses were isolated or identified. Clinical features and pathological studies closely paralleled the reported experience in Sarawak and Taiwan. The uniform necropsy findings of necrotizing brain-stem encephalitis coupled with essentially normal myocardial histology, in concert with the concurrent and consistent detection of EV71 points to a primary EV71 encephalitis; as yet unclear neurogenic mechanisms may account for the cardiovascular manifestations.
Breast Cancer Outcomes as Defined by the Estrogen Receptor, Progesterone Receptor, and Human Growth Factor Receptor-2 in a Multi-ethnic Asian Country

Subramaniam S, Bhoo-Pathy N, Taib NA, Tan GH, See MH, Jamaris S, et al.

World J Surg, 2015 Oct;39(10):2450-8.
PMID: 26138872 DOI: 10.1007/s00268-015-3133-2

Breast cancer can be divided into four subtypes based on the expressions of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 (HER2). Each subtype has different clinicopathological features and outcomes.
Screening for microsatellite instability in colorectal carcinoma: Practical utility of immunohistochemistry and PCR with fragment analysis in a diagnostic histopathology setting

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.

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