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Fulltext Human telomerase reverse transcriptase expression in ovarian tumors

Maraei AA, Hatta AZ, Shiran MS, Tan GC

Indian J Pathol Microbiol, 2012 Apr-Jun;55(2):187-91.
PMID: 22771641 DOI: 10.4103/0377-4929.97865

Ovarian cancer is the 6 th most common cancer among women. In ovarian tumors, the borderline category is not well defined due to the difficulty in assessing stromal invasion. The World Health Organization (WHO) defined it as tumor that lacks obvious invasion of the stroma with mitotic activity and nuclear abnormalities intermediate between clearly benign and unquestionably malignant. Telomerase is expressed in many human cancers and is hence a potential biomarker for cancer. Immunohistochemical study of anti-human telomerase enzyme reverse transcriptase (hTERT) antibody allows direct visualization of its expression. The aim of this study was to determine the expression of hTERT and serum CA-125 level in ovarian epithelial tumors, and their ability to distinguish borderline tumor from malignancy.
Fulltext Mucosal malignant melanoma of the maxillary sinus

Norhafizah M, Mustafa WM, Sabariah AR, Shiran MS, Pathmanathan R

Med J Malaysia, 2010 Sep;65(3):218-20.
PMID: 21939172

Mucosal malignant melanoma (MMM) is an aggressive tumour occurring in the upper respiratory tract. It is rare compared to malignant melanoma of the skin. We report a case of a 53-year-old man with left paranasal swelling. A biopsy showed high-grade spindle cell tumour. Subsequently a subtotal maxillectomy was performed. Histopathological examination revealed a hypercellular tumour composed of mixed spindle and epitheloid cells with very occasional intracytoplasmic melanin pigment. The malignant cells were immunopositive for vimentin, S-100 protein and HMB-45. It was diagnosed as mucosal malignant melanoma (MMM). This article illustrates a rare case of MMM where the diagnosis may be missed or delayed without proper histopathological examination that include meticulous search for melanin pigment and appropriate immunohistochemical stains to confirm the diagnosis. Malignant melanoma can mimic many other types of high-grade malignancy and should be considered as a differential diagnosis in many of these instances.
Fulltext Multifocal nodal and extranodal Rosai-Dorfman disease initially diagnosed as histiocytic lymphoma

Shiran MS, Tan GC, Kenali MS, Sabariah AR, Pathmanathan R

Malays J Pathol, 2008 Jun;30(1):63-5.
PMID: 19108414 MyJurnal

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy (SHML), is a systemic disease involving nodal and extranodal tissues. We report a 48-year-old female with recurrent nasal obstruction due to polypoidal masses involving the nasal sinuses, turbinates and septum bilaterally, and lumps in the right infra-orbital region and region of the right lacrimal sac. A 4 cm right upper neck mass was also noted, which was initially diagnosed as histiocytic lymphoma. Histopathology of the nasal and infraorbital lesions revealed fibro-inflammatory masses containing histiocytic cells with large vesicular nuclei and abundant foamy cytoplasm exhibiting emperipolesis and lymphophagocytosis, admixed with scattered plasma cells and lymphocytes. These histiocytes revealed immunohistochemical positivity for S-100 protein and CD68, but were negative for CDla. The findings supported a diagnosis of RDD. This report serves to remind pathologists and clinicians of the extranodal manifestations of RDD and its potential confusion with lymphomas.
Fulltext Small cell variant of anaplastic large cell lymphoma with positive immunoreactivity for CD99

Shiran MS, Tan GC, Sabariah AR, Chye PC, Pathmanathan R

Med J Malaysia, 2008 Jun;63(2):150-1.
PMID: 18942305 MyJurnal

A 13 year old boy presented with a huge mass on his right arm of 6 months duration. Histopathological examination revealed sheets of malignant small round blue cells with immunopositivity for LCA, CD43, CD45Ro, CD30, EMA, ALK-1 and CD99, and negativity for CD20, TdT, myogenin, myoD1, NSE, bcl-6, bcl-2 and CD10. Fluorescent In-Situ Hybridization (FISH) testing excluded the diagnosis of Ewing's sarcoma/PNET. Pathologists need to be aware of the diagnosis of a small cell variant of ALCL, as well as of the fact that CD99 expression commonly occurs in cases of ALK-positive ALCL, in order to distinguish this entity from Ewing's sarcoma/PNET.
Clear cell "sugar" tumour of the lung: a case report

Shiran MS, Tan GC, Arunachalam N, Sabariah AR, Pathmanathan R

Malays J Pathol, 2006 Dec;28(2):113-6.
PMID: 18376801

We report a case of clear cell "sugar" tumour of the lung (CCTL) occurring in a 26-year-old lady. The patient was asymptomatic and the lesion was picked up in the course of a pre-employment medical examination. A well-defined 5 cm nodule in the right lower lobe was detected on routine chest X-Ray. Microscopical examination of the coin lesion showed clear cells containing abundant diastase-sensitive intracytoplasmic glycogen, as demohstrated with periodic acid-Schiff stains. Tumour immunoreactivity for HMB-45 and non-reactivity for cytokeratin support the histological diagnosis. To our knowledge, this is the first reported case of CCTL in Malaysia.
Large retrosternal parathyroid carcinoma with primary hyperparathyroidism

Tan GC, Shiran MS, Swaminathan M, Phang KS, Rohaizak M

Asian J Surg, 2007 Oct;30(4):286-9.
PMID: 17962134

Parathyroid carcinoma is an uncommon cause of parathyroid hormone (PTH)-dependent hypercalcaemia, accounting for less than 1% of all cases of hyperparathyroidism. Parathyroid carcinoma is an indolent tumour with rather low malignant potential. Consideration of parathyroid carcinoma in the differential diagnosis of hypercalcaemic disorders is important because the morbidity and mortality are substantial and the best prognosis is associated with early recognition and surgical resection. Clinical indicators favouring parathyroid carcinoma over benign disease include markedly raised serum calcium levels, PTH and alkaline phosphatase. A palpable neck mass with both kidney and skeletal manifestations also give a high index of suspicion of parathyroid carcinoma. Histopathology alone is not sufficient to diagnose parathyroid cancer; it has to be correlated with the clinical findings. The initial and most effective treatment for parathyroid carcinoma is complete resection of the primary lesion, and repeated operations for recurrence are useful. The prognosis of parathyroid carcinomas is quite variable; 5-year survival rates vary from 40% to 86%, while the 10-year survival rate is approximately 49%. We report a case of parathyroid carcinoma occurring in a 55-year-old woman who presented with bone pain and hypercalcaemia.
Fulltext p63 as a complimentary basal cell specific marker to high molecular weight-cytokeratin in distinguishing prostatic carcinoma from benign prostatic lesions

Shiran MS, Tan GC, Sabariah AR, Rampal L, Phang KS

Med J Malaysia, 2007 Mar;62(1):36-9.
PMID: 17682568 MyJurnal

The diagnosis of prostatic carcinoma (Pca) on routine biopsies may be challenging, and to date the commonly used marker to distinguish prostate carcinoma from benign prostatic lesions has been High Molecular Weight-Cytokeratin (HMW-CK). However, the antigen of HMW-CK is susceptible to the effect of formalin fixation and causes frequent loss or patchy staining in the obviously benign glands. More recently, antibodies to p63 have been reported to be more sensitive than HMW-CK for the detection of prostatic basal cells. p63, a homologue of tumour suppressor gene p53, is essential for prostate development and is selectively expressed in the nuclei of basal cells of normal prostate glands. The objective of this study is to compare the sensitivity and specificity of HMW-CK and p63 in distinguishing prostatic carcinomas from benign prostatic lesions, as well as determining their positive predictive values. Seventy-two cases from HUKM (comprising 29 prostatic carcinomas and 43 benign prostatic hyperplasias) were stained for both HMW-CK and p63. The sensitivity of p63 and HMW-CK in identifying basal cells in benign glands was 88.37% and 90.70% respectively. The specificity of both reagents was 100%, and the positive predictive value for both reagents was also 100%. Thus, p63 is a useful complementary basal cell specific stain to HMW-CK, and would be very helpful to practicing pathologists in dealing with difficult cases.
Fulltext The association of nutritional risk with physical and mental health problems among elderly in a semi-urban area of Mukim Kajang, Selangor, Malaysia

Mohd Sidik S, Rozali A, Shiran MS, Sam AA

Malays J Nutr, 2004 Sep;10(2):149-58.
PMID: 22691736 MyJurnal

Imbalances and deficiencies of nutrients are particularly prevalent among the elderly, resulting in increased risk of illness and impaired outcome, as well as reduced quality of life. A cross-sectional study was conducted to assess the nutritional risk and to determine its association with physical and mental health problems among the elderly in a semiurban community in the District of Hulu Langat, Selangor. Elderly people aged 60 years and above were included in the study, conducted from 11th March to 10th May 2004. Data were collected using a questionnaire-guided interview method. The Nutrition Screening Initiative Checklist (NSI-13) was used to assess the level (low, moderate, high) of nutritional risk of the subjects. The questionnaire also included the Barthel Index, Geriatric Depression Scale (GDS-30) and Elderly Cognitive Assessment Questionnaire (ECAQ) to identify functional status, depressive symptoms and cognitive impairment respectively, among the respondents. Out of 316 elderly residents, 300 agreed to participate in the study (response rate 94.9%). Respondents aged from 60 to 93 years old and the mean age was 67.08±6.6. Prevalence of moderate and high nutritional risks were 25.3% and 36.3% respectively. Nutritional risks were found to be significantly associated with age (p=0.015), marital status (p=0.00), chronic illness (p=0.000), functional disability (p=0.000) and depressive symptoms (p=0.010). In conclusion, the health status of the elderly strongly depends on their nutritional risk. Age, marital status, chronic illness, functional disability and depressive symptoms are factors to be emphasised when assessing the nutritional risk of the elderly.
Study site: Hulu Langat District, Selangor, Malaysia
Device, Questionnaire & Scale: Nutrition Screening Initiative Checklist (NSI-13); Barthel Index; Geriatric Depression Scale (GDS-30); Elderly Cognitive Assessment Questionnaire (ECAQ)
Prevalence data: Depression 6.3%, cognitive impairment 8.3%
Fulltext Detection of epidermal growth factor receptor mutations in formalin fixed paraffin embedded biopsies in Malaysian non-small cell lung cancer patients

Shi Yeen TN, Pathmanathan R, Shiran MS, Ahmad Zaid FA, Cheah YK

J Biomed Sci, 2013 Apr 16;20:22.
PMID: 23590575 DOI: 10.1186/1423-0127-20-22

BACKGROUND: Somatic mutations of the epidermal growth factor receptor (EGFR) are reportedly associated with various responses in non-small cell lung cancer (NSCLC) patients receiving the anti-EGFR agents. Detection of the mutation therefore plays an important role in therapeutic decision making. The aim of this study was to detect EGFR mutations in formalin fixed paraffin embedded (FFPE) samples using both Scorpion ARMS and high resolution melt (HRM) assay, and to compare the sensitivity of these methods.
RESULTS: All of the mutations were found in adenocarcinoma, except one that was in squamous cell carcinoma. The mutation rate was 45.7% (221/484). Complex mutations were also observed, wherein 8 tumours carried 2 mutations and 1 tumour carried 3 mutations.
CONCLUSIONS: Both methods detected EGFR mutations in FFPE samples. HRM assays gave more EGFR positive results compared to Scorpion ARMS.
Fulltext Identification of actinomycete communities in Antarctic soil from Barrientos Island using PCR-denaturing gradient gel electrophoresis

Learn-Han L, Yoke-Kqueen C, Shiran MS, Vui-Ling CM, Nurul-Syakima AM, Son R, et al.

Genet. Mol. Res., 2012;11(1):277-91.
PMID: 22370930 DOI: 10.4238/2012.February.8.3

The diversity of specific bacteria taxa, such as the actinomycetes, has not been reported from the Antarctic island of Barrientos. The diversity of actinomycetes was estimated with two different strategies that use PCR-denaturing gradient gel electrophoresis. First, a PCR was applied, using a group-specific primer that allows selective amplification of actinomycete sequences. Second, a nested-PCR approach was used that allows the estimation of the relative abundance of actinomycetes within the bacterial community. Molecular identification, which was based on 16S rDNA sequence analysis, revealed eight genera of actinomycetes, Actinobacterium, Actinomyces, an uncultured Actinomycete, Streptomyces, Leifsonia, Frankineae, Rhodococcus, and Mycobacterium. The uncultured Actinomyces sp and Rhodococcus sp appear to be the prominent genera of actinomycetes in Barrientos Island soil. PCR-denaturing gradient gel electrophoresis patterns were used to look for correlations between actinomycete abundance and environmental characteristics, such as type of rookery and vegetation. There was a significant positive correlation between type of rookery and abundance of actinomycetes; soil samples collected from active chinstrap penguin rookeries had the highest actinomycete abundance. Vegetation type, such as moss, which could provide a microhabitat for bacteria, did not correlate significantly with actinomycete abundance.
Fulltext Analysis of Antarctic proteobacteria by PCR fingerprinting and screening for antimicrobial secondary metabolites

Lee LH, Cheah YK, Nurul Syakima AM, Shiran MS, Tang YL, Lin HP, et al.

Genet. Mol. Res., 2012;11(2):1627-41.
PMID: 22782582 DOI: 10.4238/2012.June.15.12

Fifty-seven proteobacterium species were successfully isolated from soils of Barrientos Island of the Antarctic using 11 different isolation media. Analysis of 16S rDNA sequencing of these isolates showed that they belonged to eight different genera, namely Bradyrhizobium, Sphingomonas, Methylobacterium, Caulobacter, Paracoccus, Ralstonia, Rhizobium, and Staphylococcus. All isolates were studied for capability of producing antimicrobial and antifungal secondary metabolites using high-throughput screening models. Approximately 23 (13/57) and 2% (1/57) of isolates inhibited growth of Candida albicans ATCC 10231(T) and Staphylococcus aureus ATCC 51650(T), respectively. These results indicated that proteobacterium species isolates from Antarctic could serve as potential source of useful bioactive metabolites. Enterobacterial repetitive intergenic consensus (ERIC)-PCR fingerprinting produced nine clusters and 13 single isolates, with a high D value of 0.9248. RAPD fingerprinting produced six clusters and 13 single isolates, with a relatively low D value of 0.7776. ERIC-PCR analysis proved to have better discrimination capability than RAPD analysis and generated better clustering for all proteobacterium species isolates. We conclude that ERIC-PCR is a robust, reliable and rapid molecular typing method for discriminating different genera of proteobacteria.
Fulltext Evaluation of DNA and RNA extraction methods

Edwin Shiaw CS, Shiran MS, Cheah YK, Tan GC, Sabariah AR

Med J Malaysia, 2010 Jun;65(2):133-7.
PMID: 23756798 MyJurnal

This study was done to evaluate various DNA and RNA extractions from archival FFPE tissues. A total of 30 FFPE blocks from the years of 2004 to 2006 were assessed with each modified and adapted method. Extraction protocols evaluated include the modified enzymatic extraction method (Method A), Chelex-100 extraction method (Method B), heat-induced retrieval in alkaline solution extraction method (Methods C and D) and one commercial FFPE DNA Extraction kit (Qiagen, Crawley, UK). For RNA extraction, 2 extraction protocols were evaluated including the enzymatic extraction method (Method 1), and Chelex-100 RNA extraction method (Method 2). Results show that the modified enzymatic extraction method (Method A) is an efficient DNA extraction protocol, while for RNA extraction, the enzymatic method (Method 1) and the Chelex-100 RNA extraction method (Method 2) are equally efficient RNA extraction protocols.
Fulltext Immunohistochemical study of p16 INK4A and survivin expressions in cervical squamous neoplasm

Tan GC, Norlatiffah S, Sharifah NA, Razmin G, Shiran MS, Hatta AZ, et al.

Indian J Pathol Microbiol, 2010 Jan-Mar;53(1):1-6.
PMID: 20090212 DOI: 10.4103/0377-4929.59173

Cervical cancer is the second most common cancer affecting Malaysian women. Despite the implementation of pap smear screening, many women are still diagnosed only in the advanced stage of cervical cancer. This could partly be due to failure of detection of its precursor lesions; hence the need to search for novel biomarkers to assist in the screening and diagnosis of cervical neoplasia. This study aims to determine the expression of p16INK4A and survivin as possible predictive biomarkers in cervical squamous neoplasm.
Fulltext Utility of Ki-67 and p53 in distinguishing cervical intraepithelial neoplasia 3 from squamous cell carcinoma of the cervix

Tan GC, Sharifah NA, Shiran MS, Salwati S, Hatta AZ, Paul-Ng HO

Asian Pac J Cancer Prev, 2008 Oct-Dec;9(4):781-4.
PMID: 19256776

The differentiation between cervical intraepithelial neoplasia 3 (CIN 3) and early squamous cell carcinoma (SCC) of the cervix may be difficult in certain situations. Identification of invasion beyond the basement membrane is the gold standard for the diagnosis of the latter. The objective of this study was to determine whether the use of Ki-67 and p53 could help in solving the above dilemma. This was a retrospective study on 61 cases of cervical neoplasms comprising of 25 cases of CIN 3 and 36 SCC. All cases were evaluated by immunohistochemistry using Ki-67 and p53 monoclonal antibodies. Results showed that the differences of Ki-67 and p53 expression between CIN 3 and SCC were statistically significant. In conclusion, Ki-67 and p53 may serve as helpful adjuncts to routinely-stained histological sections in differentiating between CIN 3 and SCC.
Fulltext Cutaneous mycobacterial spindle cell pseudotumour

Tan GC, Yap YP, Shiran MS, Sabariah AR, Pathmanathan R

BMJ Case Rep, 2009;2009.
PMID: 21686408 DOI: 10.1136/bcr.11.2008.1221

Mycobacterial spindle cell pseudotumour (MSCP) has been reported in various sites, including skin, lymph nodes, bone marrow, lung and spleen. Cutaneous lesions are extremely rare and the differential diagnoses include various spindle cell lesions. Literature review shows that this lesion has preponderance for upper limb involvement and occurs largely in immunosuppressed individuals. We report a case of MSCP of the skin due to atypical mycobacterium and discuss the risk of misdiagnosis as a sarcoma.
Fulltext The utility of hepatocyte paraffin 1 antibody in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma and metastatic carcinoma

Shiran MS, Isa MR, Mohd Sidik S, Rampal L, Hairuszah I, Sabariah AR

Malays J Pathol, 2006 Dec;28(2):87-92.
PMID: 18376797 MyJurnal

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and its diagnosis on routine stains is usually straightforward, except in some cases where there may be difficulty in distinguishing HCCs from metastatic carcinomas (MC) and cholangiocarcinomas (CC). Hepatocyte Paraffin 1 antibody (Hep Par 1) is a new monoclonal antibody which reacts with normal and neoplastic hepatocytes, and this study aims to determine its specificity and sensitivity in distinguishing hepatocellular carcinoma (HCC) from cholangiocarcinoma (CC) and metastatic carcinomas (MC). Hep Par 1 antibody was applied to 28 cases of HCC, 22 cases of MC from varying sites and 8 CCs, and produced a strong, diffuse, granular, cytoplasmic staining of all benign hepatocytes. 23 out of 28 cases of HCC showed heterogeneously positive staining for Hep Par 1 irrespective of their degree of differentiation, while 2 out of 8 cases of cholangiocarcinoma were positive for Hep Par 1, and all 22 cases of metastatic carcinoma were negative. The sensitivity and specificity of Hep Par 1 for HCC was 82.1% and 93.3% respectively; whereby the antibody was noted to show occasional false positivity in cases of cholangiocarcinoma and non-neoplastic bowel mucosa, while its variable staining in HCC produced false negative results in some small biopsies. Thus, Hep Par 1 should be used in a panel with other antibodies to obtain useful information in distinguishing HCC from CC and MC.
Differential microRNA expression and identification of putative miRNA targets and pathways in head and neck cancers

Nurul-Syakima AM, Yoke-Kqueen C, Sabariah AR, Shiran MS, Singh A, Learn-Han L

Int J Mol Med, 2011 Sep;28(3):327-36.
PMID: 21637912 DOI: 10.3892/ijmm.2011.714

MicroRNAs (miRNAs) are small noncoding RNAs that involved in various cancer-related cellular processes. Diverse studies on expression profiling of miRNAs have been performed and the data showed that some miRNAs are up-regulated or down-regulated in cancer. Until now, there are no data published on the miRNA expression in head and neck cancers from Malaysia. Hence, this study aimed to investigate potentially crucial miRNAs in head and neck cancer patients from Malaysian populations. A global miRNA profiling was performed on 12 samples of head and neck cancer tissue using microarray analysis followed by validation using real-time RT-PCR. Microarray analysis identified 10 miRNAs that could distinguish malignant head and neck cancer lesions from normal tissues; 7 miRNAs (hsa-miR-181a-2*, hsa-miR-29b-1*, hsa-miR-181a, hsa-miR-181b, hsa-miR-744, hsa-miR-1271 and hsa-miR-221*) were up-regulated while 3 miRNAs (hsa-miR-141, hsa-miR-95 and hsa-miR-101) were down-regulated. These miRNAs may contribute in a simple profiling strategy to identify individuals at higher risk of developing head and neck cancers, thus helping in the elucidation of the molecular mechanisms involved in head and neck cancer pathogenesis.
Alveolar rhabdomyosarcoma of the left hand with bilateral breast metastases in an adolescent female

Tan GC, Shiran MS, Hayati AR, Sharifah NA, Nuru AS, Rohaizak M

J Chin Med Assoc, 2008 Dec;71(12):639-42.
PMID: 19114329

Rhabdomyosarcoma is a common extramammary malignancy in pediatric age groups, but it rarely metastasizes to the breast. Breast rhabdomyosarcomas are commonly metastatic, with possible primary locations at the head and neck, trunk, extremities, retroperitoneum and perianal region. We report a case of primary alveolar rhabdomyosarcoma of the upper extremities in a 17-year-old adolescent female who presented with bilateral lower limb weakness and bilateral breast lumps.
C-erbB-2 onco-protein expression in breast cancer: relationship to tumour characteristics and short-term survival in Universiti Kebansaan Malaysia Medical Centre

Sharifah NA, Lee BR, Clarence-Ko CH, Tan GC, Shiran MS, Naqiyah I, et al.

Asian Pac J Cancer Prev, 2008 Oct-Dec;9(4):663-70.
PMID: 19271345

Breast cancer is the commonest cancer affecting females in Malaysia, contributing 31% of all newly diagnosed cases amongst Malaysian women. The present retrospective cohort study evaluated the relationship between cerbB- 2 onco-protein overexpression with various tumour characteristics and survival rate of breast cancer patients treated at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) between 1996-2000. CerbB- 2 oncoprotein overexpression was determined by immunohistochemistry (IHC) and tumors showing 2+ positivity were verified by Fluorescence In Situ Hybridization (FISH). One hundred and seventy two patients were eligible for the study with a short-term follow-up (median) of 5.1 years. C-erbB-2 oncoprotein overexpression correlated with lymph node positivity, oestrogen receptor (ER) and progesterone receptor (PR) negativity. Univariate analyses showed shorter disease free survival (DFS) and overall survival (OS) in patients with cerbB- 2 oncoprotein overexpression, Malay ethnicity, higher tumour grade, lymph node positivity, ER and PR negativity. In a subgroup of patients with c-erbB-2 oncoprotein overexpression, a shorter OS was observed in those with lymph node positivity, ER and PR negativity. In multivariate prognostic analysis, lymph node status, ER status and tumour grading were the strongest independent prognostic factors for both OS and DFS. However, c-erbB-2 status was not a significantly independent prognostic factor, even in subsets with lymph node positive or negative group. C-erbB-2 oncoprotein overexpression correlated well with lymph node status, ER and PR. Shorter OS and DFS were significantly observed in patients with c-erbB-2 oncoprotein overexpression. Lymph node status, ER status and tumour grading were the only three independent prognostic factors for OS and DFS in this study. Although c-erbB-2 expression is obviously important from a biological standpoint, multivariate analysis showed that it is not an independent prognostic indicator in breast carcinoma in the local population.

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