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Fulltext Mining The Cancer Genome Atlas gene expression data for lineage markers in distinguishing bladder urothelial carcinoma and prostate adenocarcinoma

Ch'ng ES

Sci Rep, 2021 03 24;11(1):6765.
PMID: 33762601 DOI: 10.1038/s41598-021-85993-x

Distinguishing bladder urothelial carcinomas from prostate adenocarcinomas for poorly differentiated carcinomas derived from the bladder neck entails the use of a panel of lineage markers to help make this distinction. Publicly available The Cancer Genome Atlas (TCGA) gene expression data provides an avenue to examine utilities of these markers. This study aimed to verify expressions of urothelial and prostate lineage markers in the respective carcinomas and to seek the relative importance of these markers in making this distinction. Gene expressions of these markers were downloaded from TCGA Pan-Cancer database for bladder and prostate carcinomas. Differential gene expressions of these markers were analyzed. Standard linear discriminant analyses were applied to establish the relative importance of these markers in lineage determination and to construct the model best in making the distinction. This study shows that all urothelial lineage genes except for the gene for uroplakin III were significantly expressed in bladder urothelial carcinomas (p 0.3). All prostate lineage genes were significantly expressed in prostate adenocarcinomas(p 0.3). Combination of gene expressions for uroplakin II, S100P, NKX3.1 and PSA approached 100% accuracy in tumor classification both in the training and validation sets. Mining gene expression data, a combination of four lineage markers helps distinguish between bladder urothelial carcinomas and prostate adenocarcinomas.
Head and Neck Cancer

Ch'ng ES

N Engl J Med, 2020 May 14;382(20):e57.
PMID: 32402178 DOI: 10.1056/NEJMc2001370
Prognosis of primary breast salivary gland-type carcinoma: a propensity score-matching analysis with invasive carcinoma of no special type based on the SEER database for years 2010-2020

Ch'ng ES

Breast Cancer, 2024 May;31(3):496-506.
PMID: 38546966 DOI: 10.1007/s12282-024-01564-8

BACKGROUND: Primary breast salivary gland-type carcinoma has weak evidence to support its management due to its rare occurrence and limited data regarding its clinicopathological features and prognosis. Therefore, this study aimed to assess clinicopathological features and prognosis for this type of carcinoma diagnosed over the past decade and compared those to the common breast invasive carcinoma of no special type (NST).
METHODS: This study used the Surveillance, Epidemiology, and End Results (SEER) database to extract data regarding primary breast salivary gland-type carcinoma. Using a propensity score-matching approach, the prognosis was compared with invasive carcinoma, NST.
RESULTS: This study included 488 cases of salivary gland-type carcinoma and 375,660 cases of invasive carcinoma, NST, giving an occurrence ratio of 1 to 770. Adenoid cystic carcinoma (81%) formed the majority of salivary gland-type carcinoma, followed by secretory carcinoma (13%). For salivary gland-type carcinoma, acinic cell carcinoma histological type, tumor grade 3, HER2-overexpressed status, and higher AJCC stage groups were significant worse prognostic factors for breast cancer-specific survival in univariate analyses (p
Fulltext Roles of Sema4D and Plexin-B1 in tumor progression

Ch'ng ES, Kumanogoh A

Mol. Cancer, 2010;9:251.
PMID: 20858260 DOI: 10.1186/1476-4598-9-251

Sema4D, also known as CD100, is a protein belonging to class IV semaphorin. Its physiologic roles in the immune and nervous systems have been extensively explored. However, the roles of Sema4D have extended beyond these traditionally studied territories. Via interaction with its high affinity receptor Plexin-B1, Sema4D-Plexin-B1 involvement in tumor progression is strongly implied. Here, we critically review and delineate the Sema4D-Plexin-B1 interaction in many facets of tumor progression: tumor angiogenesis, regulation of tumor-associated macrophages and control of invasive growth. We correlate the in vitro and in vivo experimental data with the clinical study outcomes, and present a molecular mechanistic basis accounting for the intriguingly contradicting results from these recent studies.
The journey of Malaysian external quality assurance program for general diagnostic histopathology

Ch'ng ES, Othman NH

Malays J Pathol, 2021 Apr;43(1):19-23.
PMID: 33903301

International Academy of Pathology, Malaysian Division has initiated and run the external quality assurance program for general diagnostic histopathology since the year 2017. This article introduces the educational philosophy of this external quality assurance program and the technicalities in running such a national program. Challenges in ensuring the successful running of this program to gain wide acceptance by histopathology laboratories in Malaysia as well as experience in overcoming these challenges are detailed. This article charts the future direction of this external quality assurance program.
Low cost immunohistochemistry bench for developing countries

Ch'ng ES, Khiro FI

Malays J Pathol, 2018 Aug;40(2):209-211.
PMID: 30173241

No abstract available.
Fulltext Anti-inflammatory Properties of Stingless Bee Honey May Reduce the Severity of Pulmonary Manifestations in COVID-19 Infections?

Ch'ng ES, Tang TH

Malays J Med Sci, 2020 May;27(3):150-152.
PMID: 32684816 DOI: 10.21315/mjms2020.27.3.16
Fulltext Breast Tumor Angiogenesis and Tumor-Associated Macrophages: Histopathologist's Perspective

Ch'ng ES, Jaafar H, Tuan Sharif SE

Patholog Res Int, 2011;2011:572706.
PMID: 21747968 DOI: 10.4061/2011/572706

Much progress has been made since the conceptualization of tumor angiogenesis-the induction of growth of new blood vessels by tumor-as a salient feature of clinically significant primary or metastatic cancers. From a practicing histopathologist's point of view, we appraise the application of this concept in breast cancer with particular reference to the evaluation of proangiogenic factors and the assessment of new microvessels in histopathological examination. Recently, much focus has also been centered on the active roles played by tumor-associated macrophages in relation to tumor angiogenesis. We review the literature; many data supporting this facet of tumor angiogenesis were derived from the breast cancer models. We scrutinize the large body of clinical evidence exploring the link between the tumor-associated macrophages and breast tumor angiogenesis and discuss particularly the methodology and limitations of incorporating such an assessment in histopathological examination.
Characteristics of invasive breast ductal carcinoma, NOS, diagnosed in a tertiary institution in the East Coast of Malaysia with a focus on tumor angiogenesis

Ch'ng ES, Tuan Sharif SE, Jaafar H

Asian Pac J Cancer Prev, 2012;13(9):4445-52.
PMID: 23167359

BACKGROUND: Prognosis of breast cancer depends on classic pathological factors and also tumor angiogenesis. This study aimed to evaluate the clinicopathological factors of breast cancer in a tertiary centre with a focus on the relationship between tumor angiogenesis and clinicopathological factors.
METHODS: Clinicopathological data were retrieved from the archived formal pathology reports for surgical specimens diagnosed as invasive ductal carcinoma, NOS. Microvessels were immunohistochemically stained with anti-CD34 antibody and quantified as microvessel density.
RESULTS: At least 50% of 94 cases of invasive breast ductal carcinoma in the study were advanced stage. The majority had poor prognosis factors such as tumor size larger than 50mm (48.9%), positive lymph node metastasis (60.6%), and tumor grade III (52.1%). Higher percentages of estrogen and progesterone receptor negative cases were recorded (46.8% and 46.8% respectively). Her-2 overexpression cases and triple negative breast cancers constituted 24.5% and 22.3% respectively. Significantly higher microvessel density was observed in the younger patient age group (p=0.012). There were no significant associations between microvessel density and other clinicopathological factors (p>0.05).
CONCLUSIONS: Majority of the breast cancer patients of this institution had advanced stage disease with poorer prognostic factors as compared to other local and western studies. Breast cancer in younger patients might be more proangiogenic.
Aerosol-based airway epithelial cell delivery improves airway regeneration and repair

Kardia E, Ch'ng ES, Yahaya BH

J Tissue Eng Regen Med, 2018 02;12(2):e995-e1007.
PMID: 28105760 DOI: 10.1002/term.2421

Aerosol-based cell therapy has emerged as a novel and promising therapeutic strategy for treating lung diseases. The goal of this study was to determine the safety and efficacy of aerosol-based airway epithelial cell (AEC) delivery in the setting of acute lung injury induced by tracheal brushing in rabbit. Twenty-four hours following injury, exogenous rabbit AECs were labelled with bromodeoxyuridine and aerosolized using the MicroSprayer® Aerosolizer into the injured airway. Histopathological assessments of the injury in the trachea and lungs were quantitatively scored (1 and 5 days after cell delivery). The aerosol-based AEC delivery appeared to be a safe procedure, as cellular rejection and complications in the liver and spleen were not detected. Airway injury initiated by tracheal brushing resulted in disruption of the tracheal epithelium as well as morphological damage in the lungs that is consistent with acute lung injury. Lung injury scores were reduced following 5 days after AEC delivery (AEC-treated, 0.25 ± 0.06 vs. untreated, 0.53 ± 0.05, P
In human invasive breast ductal carcinoma, tumor stromal macrophages and tumor nest macrophages have distinct relationships with clinicopathological parameters and tumor angiogenesis

Ch'ng ES, Tuan Sharif SE, Jaafar H

Virchows Arch, 2013 Mar;462(3):257-67.
PMID: 23283409 DOI: 10.1007/s00428-012-1362-4

Tumor-associated macrophages play a crucial role in breast cancer progression and tumor angiogenesis. However, evaluation of tumor-associated macrophages incorporating their histological locations is lacking. The aim of this study was to clarify whether macrophages in tumor stroma and macrophages in tumor cell nests have distinctive properties in relation to pertinent breast cancer clinicopathological parameters and tumor angiogenesis. In 94 human invasive breast ductal carcinomas, tumor-associated macrophages were immunostained with anti-CD68 antibody and counted or graded according to these histological locations. Microvessels were immunostained with anti-CD34 antibody and counted for microvessel density. We found that the presence of tumor stromal and tumor nest macrophages was closely correlated (p = 0.001). Both tumor stromal and tumor nest macrophages were associated with mitotic count (p = 0.001 and p = 0.037, respectively). However, only higher tumor stromal macrophage grades were associated with higher tumor grades (p = 0.004) and negative estrogen receptor status (p = 0.007). Multivariate analysis showed that tumors with a high mitotic count score (score 3 vs. scores 1 and 2) had a higher tumor stromal macrophage density (Grades III and IV) when adjusted for tumor size, tubule formation, and estrogen receptor status (odds ratio 3.41, p = 0.010). The tumor nest macrophage count significantly correlated with the microvessel density (p
Dermatofibrosarcoma protuberans of the scalp: therapeutic challenges

Kanesen D, Zakaria Z, Ch'ng ES, Nandrajog P, Kandasamy R

ANZ J Surg, 2019 03;89(3):261-264.
PMID: 28513108 DOI: 10.1111/ans.14040
A Case Report of Traumatic Ulcerative Granuloma With Stromal Eosinophilia (TUGSE): Clinical and Histopathological Diagnostic Challenges

Mohamad AF, Abdul Rahman NR, Ch'ng ES

Cureus, 2023 Nov;15(11):e48481.
PMID: 38073909 DOI: 10.7759/cureus.48481

Traumatic ulcerative granuloma with stromal eosinophilia is a reactive, self-limiting ulcer within the oral cavity; however, clinically, it mimics a malignant ulcer. Here, we report the case of a 13-year-old boy who presented with a painful solitary indurated ulcer at the lower lip for a week. Histopathological examination revealed an ulcerated lesion with significant infiltration of eosinophils, small lymphocytes, and large lymphoid cells. Further immunohistochemistry showed the inflammatory cells were CD3-positive T cells and CD68-positive, with a minority of the cell population showing CD30 positivity. CD1a-positive dendritic cells were also observed. We discuss the clinical and histopathological differential diagnoses of Langerhans cell histiocytosis and CD30-positive T-cell lymphoproliferative disorders and how to correlate them in formulating the final diagnosis.
Fulltext A Fuzzy-C-Means-Clustering Approach: Quantifying Chromatin Pattern of Non-Neoplastic Cervical Squamous Cells

Tang JR, Mat Isa NA, Ch'ng ES

PLoS One, 2015;10(11):e0142830.
PMID: 26560331 DOI: 10.1371/journal.pone.0142830

Despite the effectiveness of Pap-smear test in reducing the mortality rate due to cervical cancer, the criteria of the reporting standard of the Pap-smear test are mostly qualitative in nature. This study addresses the issue on how to define the criteria in a more quantitative and definite term. A negative Pap-smear test result, i.e. negative for intraepithelial lesion or malignancy (NILM), is qualitatively defined to have evenly distributed, finely granular chromatin in the nuclei of cervical squamous cells. To quantify this chromatin pattern, this study employed Fuzzy C-Means clustering as the segmentation technique, enabling different degrees of chromatin segmentation to be performed on sample images of non-neoplastic squamous cells. From the simulation results, a model representing the chromatin distribution of non-neoplastic cervical squamous cell is constructed with the following quantitative characteristics: at the best representative sensitivity level 4 based on statistical analysis and human experts' feedbacks, a nucleus of non-neoplastic squamous cell has an average of 67 chromatins with a total area of 10.827 μm2; the average distance between the nearest chromatin pair is 0.508 μm and the average eccentricity of the chromatin is 0.47.
Fulltext Evaluating Nuclear Membrane Irregularity for the Classification of Cervical Squamous Epithelial Cells

Tang JR, Mat Isa NA, Ch'ng ES

PLoS One, 2016;11(10):e0164389.
PMID: 27741266 DOI: 10.1371/journal.pone.0164389

Pap test involves searching of morphological changes in cervical squamous epithelial cells by pathologists or cytotechnologists to identify potential cancerous cells in the cervix. Nuclear membrane irregularity is one of the morphological changes of malignancy. This paper proposes two novel techniques for the evaluation of nuclear membrane irregularity. The first technique, namely, penalty-driven smoothing analysis, introduces different penalty values for nuclear membrane contour with different degrees of irregularity. The second technique, which can be subdivided into mean- or median-type residual-based analysis, computes the number of points of nuclear membrane contour that deviates from the mean or median of the nuclear membrane contour. Performance of the proposed techniques was compared to three state-of-the-art techniques, namely, radial asymmetric, shape factor, and rim difference. Friedman and post hoc tests using Holm, Shaffer, and Bergmann procedures returned significant differences for all the three classes, i.e., negative for intraepithelial lesion or malignancy (NILM) versus low grade squamous intraepithelial lesion (LSIL), NILM versus high grade squamous intraepithelial lesion (HSIL), and LSIL versus HSIL when the span value equaled 3 was employed with linear penalty function. When span values equaled 5, 7, and 9, NILM versus LSIL and HSIL showed significant differences regardless of the penalty functions. In addition, the results of penalty-driven smoothing analysis were comparable with those of other state-of-the-art techniques. Residual-based analysis returned significant differences for the comparison among the three diagnostic classes. Findings of this study proved the significance of nuclear membrane irregularity as one of the features to differentiate the different diagnostic classes of cervical squamous epithelial cells.
Fulltext BRAF V600E Mutation in Ameloblastoma: A Systematic Review and Meta-Analysis

Mamat Yusof MN, Ch'ng ES, Radhiah Abdul Rahman N

Cancers (Basel), 2022 Nov 14;14(22).
PMID: 36428683 DOI: 10.3390/cancers14225593

The discovery that ameloblastoma has a high mutation incidence of BRAF V600E may enable a better investigation of pathophysiology. However, there is inconsistent evidence regarding this mutation occurrence and its association with clinical information. This systematic review and meta-analysis aim to pool the overall mutation prevalence of BRAF V600E in reported ameloblastoma cases and to determine its association with patient demographic and clinicopathological features. Following the PRISMA guidelines, a comprehensive article search was conducted through four databases (Scopus, Google Scholar, PubMed, and Web of Science). Seventeen articles between 2014 and 2022 met the inclusion criteria with 833 ameloblastoma cases. For each included study, the significance of BRAF V600E on the outcome parameters was determined using odd ratios and 95% confidence intervals. Meta-analysis prevalence of BRAF V600E in ameloblastoma was 70.49%, and a significant meta-analysis association was reported for those younger than 54 years old and in the mandible. On the contrary, other factors, such as sex, histological variants, and recurrence, were insignificant. As a result of the significant outcome of BRAF V600E mutation in ameloblastoma pathogenesis, targeted therapy formulation can be developed with this handful of evidence.
Fulltext Dual thyroid ectopia with graves' disease: a case report and a review of the literature

Tan TH, Lee BN, Amir Hassan SZ, Ch'ng ES, Hussein Z

Nucl Med Mol Imaging, 2012 Dec;46(4):300-3.
PMID: 24900078 DOI: 10.1007/s13139-012-0160-x

Ectopic thyroid or thyroid ectopia is a rare developmental anomaly with the prevalence of 1 per 100,000-300,000 population. Even rarer, such an anomaly manifests as dual thyroid ectopia. To our best knowledge, only one case has been reported on dual thyroid ectopia with Graves' disease in the English literature. We present here a case of dual thyroid ectopia complicated by Graves' disease, whereby the diagnosis was rendered through judicious use of various diagnostic modalities coupled with a close clinical follow-up. In this case, therapeutic consideration should be personalized with proper informed consent of the patient.
Unravelling the diagnostic and therapeutic potentialities of a novel RNA aptamer isolated against human pituitary tumour transforming gene 1 (PTTG1) protein

Prabu SS, Ch'ng ES, Woon PY, Chen JH, Tang TH, Citartan M

Anal Chim Acta, 2020 Nov 22;1138:181-190.
PMID: 33161980 DOI: 10.1016/j.aca.2020.09.038

Human Pituitary Tumour Transforming Gene 1 (PTTG1) is an oncoprotein involved in maintaining chromosome stability and acts as a biomarker for a panel of cancers. In this study, we endeavoured to generate an RNA aptamer against PTTG1. The RNA aptamer, SECURA-3 has an estimated equilibrium dissociation constant of 16.41 ± 6.4 nM. The aptamer was successfully harnessed in several diagnostic platforms including ELASA, aptamer-based dot blot and aptamer-based western blot. SECURA-3 was also unveiled as a potential probe that could replace its counterpart antibody in the histostaining-based detection of PTTG1 in HeLa and MCF-7 formalin-fixed paraffin-embedded cell blocks. In the aspect of therapeutics, SECURA-3 RNA aptamer demonstrates an antagonistic effect by antagonizing the interaction between PTTG1 and CXCR2, as revealed in the in vitro competitive nitrocellulose filter binding assay and dual-luciferase reporter assay in HeLa cells. As the first anti-PTTG1 aptamer, SECURA-3 RNA aptamer has immense diagnostic and therapeutic properties.
Aerosolised Mesenchymal Stem Cells Expressing Angiopoietin-1 Enhances Airway Repair

Halim NSS, Ch'ng ES, Kardia E, Ali SA, Radzi R, Yahaya BH

Stem Cell Rev Rep, 2019 02;15(1):112-125.
PMID: 30178289 DOI: 10.1007/s12015-018-9844-7

BACKGROUND: The aim of this study was to investigate the effects of MSCs and MSC-expressing ANGPT1 (MSC-pANGPT1) treatment via aerosolisation in alleviating the asthma-related airway inflammation in the rabbit model.
METHODS: Rabbits were sensitised and challenged with both intraperitoneal injection and inhalation of ovalbumin (Ova). MSCs and MSC-pANGPT1 cells were aerosolised into rabbit lungs using the MicroSprayer® Aerosolizer Model IA-1B 48 h after injury. The post mortem was performed 3 days following cell delivery. Histopathological assessments of the lung tissues and inflammatory response were quantitatively scored following treatments.
RESULT(S): Administration of aerosolised MSCs and MSC-pANGPT1 were significantly reduced inflammation of the airways (p
Fulltext Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice

Jayasingam SD, Citartan M, Thang TH, Mat Zin AA, Ang KC, Ch'ng ES

Front Oncol, 2019;9:1512.
PMID: 32039007 DOI: 10.3389/fonc.2019.01512

Tumor-associated macrophages (TAMs) as immune cells within the tumor microenvironment have gained much interests as basic science regarding their roles in tumor progression unfolds. Better understanding of their polarization into pro-tumoral phenotype to promote tumor growth, tumor angiogenesis, immune evasion, and tumor metastasis has prompted various studies to investigate their clinical significance as a biomarker of predictive and prognostic value across different cancer types. Yet, the methodologies to investigate the polarization phenomena in solid tumor tissue vary. Nonetheless, quantifying the ratio of M1 to M2 TAMs has emerged to be a prevailing parameter to evaluate this polarization phenomena for clinical application. This mini-review focuses on recent studies exploring clinical significance of M1/M2 TAM ratio in human cancer tissue and critically evaluates the technicalities and challenges in quantifying this parameter for routine clinical practice. Immunohistochemistry appears to be the preferred methodology for M1/M2 TAM evaluation as it is readily available in clinical laboratories, albeit with certain limitations. Recommendations are made to standardize the quantification of TAMs for better transition into clinical practice and for better comparison among studies in various populations of patients and cancer types.

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