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Fulltext Epidermal growth factor receptor (EGFR) gene alteration and protein overexpression in Malaysian triple-negative breast cancer (TNBC) cohort

Zakaria Z, Zulkifle MF, Wan Hasan WAN, Azhari AK, Abdul Raub SH, Eswaran J, et al.

Onco Targets Ther, 2019;12:7749-7756.
PMID: 31571924 DOI: 10.2147/OTT.S214611

Background: Epidermal growth factor receptor (EGFR) is a member of the ErbB family of tyrosine kinase receptor proteins that plays important roles in tumour cell survival and proliferation. EGFR has been reported to be overexpressed in up to 78% of triple-negative breast cancer (TNBC) cases suggesting it as a potential therapeutic target. The clinical trials of anti-EGFR agents in breast cancer showed low response rates. However, a subgroup of patients demonstrated response to EGFR inhibitors highlighting the necessity to stratify patients, who might benefit from effective combination therapy that could include anti EGFR-agents. Population variability in EGFR expression warrants systematic evaluation in specific populations.
Purpose: To study EGFR alterations and expressions in a multi ethnic Malaysian TNBC patient cohort to determine the possibility of using anti-EGFR combinatorial therapy for this population.
Patients and methods: In this study, we evaluated 58 cases of Malaysian TNBC patient samples for EGFR gene copy number alteration and EGFR protein overexpression using fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) methods, respectively.
Results: EGFR protein overexpression was observed in about 30% while 15.5% displayed high EGFR copy number including 5.17% gene amplification and over 10% high polysomy. There is a positive correlation between EGFR protein overexpression and gene copy number and over expression of EGFR is observed in ten out of the 48 low copy number cases (20.9%) without gene amplification.
Conclusion: This study provides the first glimpse of EGFR alterations and expressions in a multi ethnic Malaysian TNBC patient cohort emphasising the need for the nationwide large scale EGFR expression evaluation in Malaysia.
Intrathyroidal oxyphilic parathyroid carcinoma: A potential diagnostic caveat in cytology?

Wong YP, Sharifah NA, Tan GC, Gill AJ, Ali SZ

Diagn Cytopathol, 2016 May 26.
PMID: 27229757 DOI: 10.1002/dc.23493

Oxyphilic (oncocytic) parathyroid lesions are very uncommon and their cytological features are rarely described. Due to the similarities in anatomical location and indistinguishable cytomorphological features, these lesions are easily confused with neoplastic and non-neoplastic thyroid lesions on fine needle aspiration (FNA). The diagnosis becomes more challenging in cases of unusual intrathyroidal location of the parathyroid lesions in the absence of clinical evidence of hyperparathyroidism, which simulate thyroid nodules clinically. We describe a case of intrathyroidal oxyphilic parathyroid carcinoma in a 66-year-old female, who presented with a dominant left "thyroid" nodule. FNA smears were cellular, comprising predominantly of oxyphilic cells arranged in papillary-like architecture with occasional nuclear grooves, which was mistaken for oncocytic variant of papillary carcinoma of the thyroid. The histological diagnosis of oxyphilic parathyroid "adenoma" was made following total thyroidectomy. The tumor, unfortunately, recurred 7 years later with associated multiple lung metastases. When dealing with thyroid lesions comprising predominantly of oncocytic cells, one should consider oxyphilic parathyroid neoplasms as one of the differential diagnosis. In difficult equivocal cases, a panel of immunocytochemical stains (PTH, GATA3, TTF-1, PAX8, and thyroglobulin) can be helpful. In addition, a combination of valuable clinical, radiological, and laboratory data, including serum calcium and parathyroid hormone levels are key to arriving at an accurate cytological diagnosis. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc.
CYP1A1 MspI Polymorphism and Cervical Carcinoma Risk in the Multi-Ethnic Population of Malaysia: a Case-Control Study

Tan YH, Sidik SM, Syed Husain SN, Lye MS, Chong PP

Asian Pac J Cancer Prev, 2016;17(1):57-64.
PMID: 26838255

BACKGROUND: Tobacco smoking is considered a risk factor for cervical cancer development due to the presence of tobacco based carcinogenic metabolites in cervical cells of female smokers. In this study, we investigated the role of the T3801C (MspI) polymorphism of CYP1A1, a gene encoding an enzyme necessary for the initiation of tobacco based carcinogen metabolism, on cervical cancer risk. The T to C substitution may alter CYP1A1 activities, potentially elevating cervical cancer risk. Since results of gene-disease association studies vary according to the study population, the multi-ethnic population of Malaysia provides an excellent representative cohort for identifying and comparing the cervical cancer risk among the 3 major ethnics in Southeast Asia in relation to CYP1A1 MspI polymorphism.
MATERIALS AND METHODS: A total of 195 Thin Prep Pap smear samples from HPV negative and cancer free females were randomly selected as controls while 106 formalin fixed paraffin embedded samples from females with invasive cervical cancer were randomly selected for the cases group. The polymorphisms were identified using restriction fragment length polymorphism (RFLP) PCR.
RESULTS: We found no significant associations between CYP1A1 MspI polymorphism and cervical cancer in the general Malaysian female population. However, upon ethnic stratification, the variant C/C genotype was significantly associated with a 4.66-fold increase in cervical cancer risk in Malay females (95% CI= 1.21-17.9; p=0.03). No significant association was observed in the Chinese and Indian females. Additionally, there were no significant associations in the dominant model and allele frequency model analysis in both the general and ethnically stratified female population of Malaysia.
CONCLUSIONS: Our findings suggest that the C/C genotype of CYP1A1 MspI polymorphism is associated with the development of cervical carcinoma in the Malay females of Malaysia.
Fulltext Vitamin A, C, E and risk of breast cancer according to menopausal status in Malaysia

Mohd Razif Shahril, Suhaina Sulaiman, Sharifah Wajihah Wafa, Sharifah Noor Akmal

Malaysian Journal of Public Health Medicine, 2016;16(2):72-79.
MyJurnal

Vitamin A, C and E intake has been shown to play a role in the etiology of breast cancer, but the findings have been
inconsistent and limited to developed countries with higher cancer incidence. Therefore, the aim of this study is to
examine the association of premenopausal and postmenopausal breast cancer risk with vitamin A, C and E intake from
dietary sources. This is a population based case-control study conducted in Malaysian population among 382 breast cancer
patients and 382 control group. Dietary intake was assessed via an interviewer-administered food frequency
questionnaire. Logistic regression was used to compute odds ratios (OR) with 95% confidence intervals (CI) and a broad
range of potential confounders were included in analysis. The results of this study shows a significant decreased risk of
breast cancer among premenopausal (ORQ4 to Q1=0.38, 95% CI, 0.12 – 0.55, p-trend=0.001) and postmenopausal (ORQ4 to
Q1=0.26, 95% CI, 0.03 – 0.75, p-trend=0.017) women was observed in the highest quartile of beta-carotene intake.
Meanwhile, a higher intake of vitamin C showed significantly lowered risk only for premenopausal women (ORQ4 to
Q1=0.13, 95% CI, 0.03 – 0.32, p-trend=0.001). As a conclusion, beta-carotene intake was independently related to pre- and
postmenopausal breast cancer risk, while vitamin C intake was associated with decreased risk among premenopausal
women only. However, no association was observed for vitamin A especially retinol and vitamin E intake from dietary
sources.
Fulltext Can we confidently diagnose pilomatricoma with fine needle aspiration cytology?

Wong YP, Masir N, Sharifah NA

Malays J Med Sci, 2015 Jan-Feb;22(1):84-8.
PMID: 25892955 MyJurnal

Pilomatricomas can be confidently diagnosed cytologically due to their characteristic cytomorphological features. However, these lesions are rarely encountered by cytopathologists and thus pose a diagnostic dilemma to even experienced individuals, especially when the lesions are focally sampled. We describe two cases of histologically confirmed pilomatricoma. The first case is of a 13-year-old boy with posterior cervical 'lymphadenopathy', and the second one is of a 12-year-old girl with a lower cheek swelling. Both aspirates comprised predominantly atypical basal-like cells, with prominent nucleoli. 'Ghost cells' were readily identified by cell block in case two, but cell block in case one yielded no diagnostic material. In case two, pilomatricoma was accurately diagnosed pre-operatively. A cytological suspicion of a neoplastic process was raised in case one. Despite being diagnostically challenging, pilomatricoma can be diagnosed with careful observation of two unique cytological features of the lesions: (1) pathognomonic 'ghost cells' and (2) irregular, saw-toothed, loosely cohesive basaloid cells, with prominent nucleoli. The role of thorough sampling of the lesion, with multiple passes of various sites, cannot be overemphasized.
Dendritic fibromyxolipoma: a variant of spindle cell lipoma with extensive myxoid change, with cytogenetic evidence

Wong YP, Chia WK, Low SF, Mohamed-Haflah NH, Sharifah NA

Pathol. Int., 2014 Jul;64(7):346-51.
PMID: 25047505 DOI: 10.1111/pin.12176

Dendritic fibromyxolipoma (DFML), a rare, recently described distinct benign soft tissue tumor, has many clinicopathological features reminiscent of spindle cell lipoma and solitary fibrous tumor with myxoid change. It is distinguished histologically from both entities by the presence of spindle and stellate cells with dendritic cytoplasmic prolongations, prominent myxoid stroma with abundant keloidal collagen and occasional small plexiform vascular proliferation. We describe a case of histologically confirmed DFML of the left shoulder in a 67-year-old male, in which subsequent cytogenetic analysis revealed deletion involving 13q14.3 region in all the tumor cells, typically detected in spindle cell lipoma. In the presence of many clinicopathological similarities between DFML and spindle cell lipoma including chromosomal abnormalities, we postulate that DFML is merely a rare variant of spindle cell lipoma with extensive myxoid degeneration, and may not be considered as a separate entity. The possible differential diagnosis and their distinguishing features are briefly discussed.
Dietary carbohydrate, fiber and sugar and risk of breast cancer according to menopausal status in Malaysia

Sulaiman S, Shahril MR, Wafa SW, Shaharudin SH, Hussin SN

Asian Pac J Cancer Prev, 2014;15(14):5959-64.
PMID: 25081729

BACKGROUND: Dietary carbohydrate, fiber and sugar intake has been shown to play a role in the etiology of breast cancer, but the findings have been inconsistent and limited to developed countries with higher cancer incidence.
OBJECTIVE: To examine the association of premenopausal and postmenopausal breast cancer risk with dietary carbohydrate, fiber and sugar intake.
MATERIALS AND METHODS: This population based case-control study was conducted in Malaysia with 382 breast cancer patients and 382 controls. Food intake pattern was assessed via an interviewer-administered food frequency questionnaire. Logistic regression was used to compute odds ratios (OR) with 95% confidence intervals (CI) and a broad range of potential confounders were included in analysis.
RESULTS: A significant two fold increased risk of breast cancer among premenopausal (OR Q4 to Q1=1.93, 95%CI: 1.53-2.61, p-trend=0.001) and postmenopausal (OR Q4 to Q1=1.87, 95%CI: 1.03-2.61, p-trend=0.045) women was observed in the highest quartile of sugar. A higher intake of dietary fiber was associated with a significantly lower breast cancer risk among both premenopausal (OR Q4 to Q1=0.31, 95%CI: 0.12-0.79, p-trend=0.009) and postmenopausal (OR Q4 to Q1=0.23, 95%CI: 0.07-0.76, p-trend=0.031) women.
CONCLUSIONS: Sugar and dietary fiber intake were independently related to pre- and postmenopausal breast cancer risk. However, no association was observed for dietary carbohydrate intake.
Fulltext Genetic alterations of chromosome 8 genes in oral cancer

Yong ZW, Zaini ZM, Kallarakkal TG, Karen-Ng LP, Rahman ZA, Ismail SM, et al.

Sci Rep, 2014;4:6073.
PMID: 25123227 DOI: 10.1038/srep06073

The clinical relevance of DNA copy number alterations in chromosome 8 were investigated in oral cancers. The copy numbers of 30 selected genes in 33 OSCC patients were detected using the multiplex ligation-dependent probe amplification (MLPA) technique. Amplifications of the EIF3E gene were found in 27.3% of the patients, MYC in 18.2%, RECQL4 in 15.2% and MYBL1 in 12.1% of patients. The most frequent gene losses found were the GATA4 gene (24.2%), FGFR1 gene (24.2%), MSRA (21.2) and CSGALNACT1 (12.1%). The co-amplification of EIF3E and RECQL4 was found in 9% of patients and showed significant association with alcohol drinkers. There was a significant association between the amplification of EIF3E gene with non-betel quid chewers and the negative lymph node status. EIF3E amplifications did not show prognostic significance on survival. Our results suggest that EIF3E may have a role in the carcinogenesis of OSCC in non-betel quid chewers.
Distribution of HPV genotypes in cervical cancer in multi- ethnic Malaysia

Hamzi Abdul Raub S, Isa NM, Zailani HA, Omar B, Abdullah MF, Mohd Amin WA, et al.

Asian Pac J Cancer Prev, 2014;15(2):651-6.
PMID: 24568473

BACKGROUND: Cervical cancer is the third commonest type of cancer among women in Malaysia. Our aim was to determine the distribution of human papilloma virus (HPV) genotypes in cervical cancer in our multi-ethnic population.
MATERIALS AND METHODS: This was a multicentre study with a total of 280 cases of cervical cancer from 4 referral centres in Malaysia, studied using real-time polymerase chain reaction (qPCR) detection of 12 high risk-HPV genotypes.
RESULTS: Overall HPV was detected in 92.5% of cases, in 95.9% of squamous cell carcinomas and 84.3%of adenocarcinomas. The five most prevalent high-risk HPV genotypes were HPV 16 (68.2%), 18 (40%), 58 (10.7%), 33 (10.4%) and 52 (10.4%). Multiple HPV infections were more prevalent (55.7%) than single HPV infections (36.8%). The percentage of HPV positive cases in Chinese, Malays and Indians were 95.5%, 91.9% and 80.0%, respectively. HPV 16 and 18 genotypes were the commonest in all ethnic groups. We found that the percentage of HPV 16 infection was significantly higher in Chinese (75.9%) compared to Malays (63.7%) and Indians (52.0%) (p<0.05), while HPV 18 was significantly higher in Malays (52.6%) compared to Chinese (25.0%) and Indians (28%) (p<0.05). Meanwhile, HPV 33 (17.9%) and 52 (15.2%) were also more commonly detected in the Chinese (p<0.05).
CONCLUSIONS: This study showed that the distribution of HPV genotype in Malaysia is similar to other Asian countries. Importantly, we found that different ethnic groups in Malaysia have different HPV genotype infection rates, which is a point to consider during the implementation of HPV vaccination.
Array comparative genomic hybridization analysis identified the chromosomal aberrations and putative genes involved in Prostate Tumorigenesis of Malaysian men

Nenny Noorina Saaid, Reena Rahayu Md Zin, Siti Aishah Md Ali, Sharifah Noor Akmal Syed Hussain, Zulkifli Zainuddin, Zubaidah Zakaria

Sains Malaysiana, 2014;43:1317-1326.

The identification of chromosomal aberrations in prostate cancer has been widely studied with several known oncogenes and tumor suppressor genes have successfully been discovered. The most frequent aberrations detected in western population were losses in chromosome 5q, 6q, 8p, 13q, 16q, 17p, 18q and gains of 7p/q and 8q. The purpose of this study was to determine the chromosomal aberrations among Malaysian men of Southeast Asia population and discover those potential genes within that chromosomal aberrant region. Thirty-six formalin-fixed paraffin embedded specimens consist of eight organ-confined prostate cancer cases, five with capsular invasion, 14 showed metastasis and nine cases had no tumor stage recorded, were analyzed by array CGH technique. Chromosomal losses were frequently detected at 4q, 6q, 8p, 13q, 18q while gains at 7q, 11q, 12p, 16q and 17q. Gain of 16q24.3 was statistically significant with tumor size. Gains of 6q25.1 and Xq12 as well as losses of 3p13-p1.2 and 13q33.1-q33.3 were significantly correlated with Gleason grade whereas 12p13.31 gain was associated with bone metastasis. Several potential genes have also been found within that aberrant region which is myopodin (4q26-q27), ROBO1 (3p13-p11.2), ERCC5 (13q33.1-q33.3) and CD9 (12p13.31), suggesting that these genes may play a role in prostate cancer progression. The chromosomal aberrations identified by array CGH analysis could provide important clues to discover potential genes associated with prostate tumorigenesis of Malaysian men.
Quantification of Her-2/Neu gene in breast cancer patients using real time-polymerase chain reaction (Q-PCR) and correlation with immunohistochemistry findings

Abdul Murad NA, Razak ZA, Hussain RM, Syed Hussain SN, Ko Ching Huat C, Che Md Ali SA, et al.

Asian Pac J Cancer Prev, 2013;14(3):1655-9.
PMID: 23679251

BACKGROUND: HER-2/neu is a proto-oncogene that encodes a transmembrane tyrosine kinase growth factor which is crucial for stimulating growth and cellular motility. Overexpression of HER-2/neu is observed in 10-35% of human breast cancers and is associated with pathogenesis, prognosis as well as response to therapy. Given the imperative role of HER-2/neu overexpression in breast cancer, it is important to determine the magnitude of amplification which may facilitate a better prognosis as well as personalized therapy in affected patients. In this study, we determined HER-2/neu protein expression by immunohistochemistry (IHC) concurrently with HER-2/neu DNA amplification by quantitative real time-polymerase chain reaction (Q-PCR).
MATERIALS AND METHODS: A total of 53 paired tissue samples from breast cancer patients were frozen-sectioned to characterize the tumour and normal tissues. Only tissues with 80% tumour cells were used in this study. For confirmation, Q-PCR was used to determine the HER-2/neu DNA amplification.
RESULTS: We found 20/53 (37.7%) of the tumour tissues to be positive for HER-2/neu protein overexpression using IHC. Out of these twenty, only 9/53 (17%) cases were in agreement with the Q-PCR results. The concordance rate between IHC and Q-PCR was 79.3%. Approximately 20.7% of positive IHC cases showed no HER-2/neu gene amplification using Q-PCR.
CONCLUSION: In conclusion, IHC can be used as an initial screening method for detection of the HER-2/neu protein overexpression. Techniques such as Q-PCR should be employed to verify the IHC results for uncertain cases as well as determination of HER-2/neu gene amplification.
FISH analysis using PPAR γ-specific probes for detection of PAX8-PPAR γ translocation in follicular thyroid neoplasms

Sharifah NA, Zakaria Z, Chia WK

Methods Mol Biol, 2013;952:187-96.
PMID: 23100233 DOI: 10.1007/978-1-62703-155-4_13

Fluorescence in situ hybridization (FISH) is increasingly gaining importance in clinical diagnostics settings. Due to the ability of the technique to detect chromosomal abnormalities in samples with low cellularity or containing a mixed population of cells even at a single-cell level, it has become more popular in cancer research and diagnosis. Here, we describe the FISH technique for detection of PAX8-PPARγ translocation in follicular thyroid neoplasms, and the optimal protocol for the detection of this fusion gene using in archival formalin-fixed paraffin-embedded (FFPE) thyroid tissue sections.
Fulltext The use of complementary and alternative medicine among Malay breast cancer survivors

Shaharudin SH, Sulaiman S, Emran NA, Shahril MR, Hussain SN

Altern Ther Health Med, 2011 Jan-Feb;17(1):50-6.
PMID: 21614944

BACKGROUND: A cross-sectional study was carried out to determine the prevalence of complementary and alternative medicine (CAM) use by breast cancer survivors.
METHODS: A descriptive survey design was developed. Information on socio-demographic characteristics, cancer clinical treatment history, and use of CAM were obtained through a modified self-administered questionnaire from 116 Malay breast cancer survivors aged 21 to 67 years who were 2 years postdiagnosis and currently undergoing follow-up treatment at breast cancer clinics at Hospital Kuala Lumpur and Universiti Kebangsaan Malaysia Medical Centre.
RESULTS: Data suggest that 64% of the participants were identified as CAM users; dietary supplements were the most common form used, followed by prayer and Malay traditional medicine. Within the wide range of dietary supplements, multivitamins were most often taken followed by spirulina, vitamin C, evening primrose oil, and herbal products. Contrary to other findings, the CAM users were found to be older, had secondary education levels, and were from middle-income households. However, there was no significant difference between CAM users and nonusers in this study. Family members played an important role as the main source of information along with doctors/health care providers, friends, and printed materials/mass media. The reasons participants gave for using CAM were mainly to assist in healing the body's inner strength, to cure cancer, and to reduce stress. Only half of the participants consulted with their physicians regarding the safety of CAM use. The participants began to use CAM while undergoing clinical treatments. Most of the participants used CAM for more than a year. About RM100 to RM149 (31.88 USD to 47.50 USD at press time) were spent monthly on CAM by 32% of the participants. The CAM use was found to be effective and beneficial for patients' disease states, and they were contented with the usage of the CAM therapies. Multivariate analysis revealed that thedecision to use or not to use CAM was not dependent on sociodemographic background or cancer clinical treatment history.
CONCLUSIONS: CAM was commonly used by breast cancer survivors as a coping mechanism to battle the disease.
Study site: Breast cancer clinics, Hospital Kuala Lumpur and Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Fat intake and its relationship with pre- and post-menopausal breast cancer risk: a case-control study in Malaysia

Sulaiman S, Shahril MR, Shaharudin SH, Emran NA, Muhammad R, Ismail F, et al.

Asian Pac J Cancer Prev, 2011;12(9):2167-78.
PMID: 22296351

BACKGROUND: Fat intake has been shown to play a role in the etiology of breast cancer, but the findings have been inconsistent.
OBJECTIVE: To assess the association of premenopausal and postmenopausal breast cancer risk with fat and fat subtypes intake.
METHODOLOGY: This is a population based case-control study conducted in Kuala Lumpur, Malaysia from January 2006 to December 2007. Food intake pattern was collected from 382 breast cancer patients and 382 control group via an interviewer-administered food frequency questionnaire. Logistic regression was used to compute odds ratios (OR) with 95% confidence intervals (CI) and a broad range of potential confounders was included in analysis.
RESULTS: This study showed that both premenopausal and postmenopausal breast cancer risk did not increase significantly with greater intake of total fat [quartile (Q) 4 versus Q1 OR=0.76, 95% CI, 0.23-2.45 and OR=1.36, 95% CI, 0.30-3.12], saturated fat (ORQ4 to Q1=1.43, 95% CI, 0.51-3.98 and ORQ4 to Q1=1.75, 95% CI, 0.62-3.40), monounsaturated fat (ORQ4 to Q1=0.96, 95% CI, 0.34-1.72 and ORQ4 to Q1=1.74, 95% CI, 0.22-2.79), polyunsaturated fat (ORQ4 to Q1=0.64, 95% CI, 0.23-1.73 and ORQ4 to Q1=0.74, 95% CI, 0.39-1.81), n-3 polyunsaturated fat (ORQ4 to Q1=1.10, 95% CI, 0.49-2.48 and ORQ4 to Q1=0.78, 95% CI, 0.28-2.18), n-6 polyunsaturated fat (ORQ4 to Q1=0.67, 95% CI, 0.24-1.84 and ORQ4 to Q1=0.71, 95% CI, 0.29-1.04) or energy intake (ORQ4 to Q1=1.52, 95% CI, 0.68-3.38 and ORQ4 to Q1=2.21, 95% CI, 0.93-3.36).
CONCLUSION: Total fat and fat subtypes were not associated with pre- and postmenopausal breast cancer risk after controlling for age, other breast cancer risk factors and energy intake. Despite the lack of association, the effects of total fat and fat subtypes intake during premenopausal years towards postmenopausal breast cancer risk still warrant investigation.
Fulltext HPV positivity and its' influencing factors among invasive cervical cancer women in Malaysia

Sharifa Ezat Wan Puteh, Norin Rahayu Samsuddin, Sharifah Noor Akmal Syed Hussain, Shamsul Azhar Shah, Syed Mohamed Aljunid

Int J Public Health Res, 2011;1(1):13-22.
MyJurnal

Accepted 10 August 2011.
Introduction Cervical cancer (CC) is the second most prevalent female cancer in Malaysia. Almost 70% of its’ causal factors are attributable to oncogenic human papillomavirus (HPV) types 16, 18 and other risk factors. HPV genotypes distributions are also noted to differ by geographical area.
Methods This was cross sectional study conducted in 2007, to determine the influencing factors of HPV positivity and prevalence of HPV infections among patients with cervical cancer in Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Patients’ paraffin-embedded cervical tissues kept in the Pathology Department from 1999 to 2007 were randomly selected. A total of 81 medical records with complete information were chosen as samples and patients were contacted for consent. Tissue samples were further derived for PCR DNA for HPV genotyping. Analyses included descriptive statistics; bivariate χ2 test and correlation were used to determine relationship between factors and HPV positivity. Significance level of less than 0.05 was taken as statistically significant.
Results Mean age of cancer diagnosis was at 52 ± 12.2 years. Women of Chinese ethnicity was the highest ethnicity to be HPV positive at 65.4% and squamous cell carcinoma was more commonly found (59.3%) compared with other types of cancers. The prevalence of HPV positivity was 92.6% with type 16 being the most common (74.1%), followed by type 33 (30.9%) and 18 (22.2%). Multiple HPV infections were a common finding at 54.3%. Factors thought to influence positivity i.e. age of intercourse, number of sexual partners, number of parity, smoking status of patients and their partners, oral contraceptive usage, presence of chronic illnesses and cancer stage were not significantly associated with HPV positivity. Increased CC severity level was not associated with increased number of HPV infections (Pearson correlation 0.58; p =0.607).
Conclusions High HPV positivity at 92.6% was found among ICC patients. Factors thought to influence HPV positivity were not significant. The top three HPV genotypes were type 16 followed by type 33 and 18. However, local women HPV serotypes findings need to be replicated in a larger population sample.
Fulltext Expression and mutational analysis of GATA3 in Malaysian breast carcinomas

Bong PN, Zakaria Z, Muhammad R, Abdullah N, Ibrahim N, Emran NA, et al.

Malays J Pathol, 2010 Dec;32(2):117-22.
PMID: 21329183 MyJurnal

The GATA3 gene is a potential tumour marker and putative tumour suppressor gene in breast cancer. Its expression is associated with better prognosis and disease free survival in breast cancer patients. We aimed to evaluate GATA3 transcriptome expression and mutation in breast carcinomas and correlate its expression with oestrogen receptor (ER), progesterone receptor (PR), lymph node (LN) status, tumour grade and c-erbB-2 expression. Twenty-two breast infiltrating ductal carcinomas and paired normal tissues were used in Branch DNA assay to detect GATA3 mRNA expression. Normalized data for GATA3 mRNA expression were grouped according to the ER, PR and LN status, tumour grade and c-erbB-2 expression of the tumours. Statistical significance was tested using t-test and ANOVA at 95% confidence interval level. Mutational analysis of GATA3 was performed by direct sequencing of the coding regions of GATA3 mRNA. Our findings showed that GATA3 gene were over-expressed and under-expressed by > 2 fold change in 12 and 4 tested samples, respectively. Eighty per cent of ER positive breast carcinomas were GATA3 positive. There was a statistically significant correlation between GATA3 expression and ER at 95% confidence interval level between the study groups. On the contrary, GATA3 expression was not statistically significant with PR, LN, tumour grade and c-erbB-2 expression in our study. In addition, we observed that there was no mutation in mRNA coding region in 16 breast carcinomas that showed GATA3 differential gene expression. Our preliminary results suggested that GATA3 is linked to the ER. This scenario suggests that GATA3 may play a crucial role in oestrogen receptor positive breast cancer patients. Whether GATA3 expression is involved in regulating tumour cell growth in oestrogen responsive breast cancer is a key question that remains to be answered.
Fulltext Identification of novel large genomic rearrangements at the BRCA1 locus in Malaysian women with breast cancer

Sharifah NA, Nurismah MI, Lee HC, Aisyah AN, Clarence-Ko CH, Naqiyah I, et al.

Cancer Epidemiol, 2010 Aug;34(4):442-7.
PMID: 20451485 DOI: 10.1016/j.canep.2010.04.010

The incidence of breast cancer has been on the rise in Malaysia. It is suggested that a subset of breast cancer cases were associated with germline mutation in breast cancer susceptibility (BRCA) genes. Most of the BRCA mutations reported in Malaysia were point mutations, small deletions and insertions. Here we report the first study of BRCA large genomic rearrangements (LGRs) in Malaysia. We aimed to detect the presence of LGRs in the BRCA genes of Malaysian patients with breast cancer.
Fulltext Gene expression patterns distinguish breast carcinomas from normal breast tissues: the Malaysian context

Pau Ni IB, Zakaria Z, Muhammad R, Abdullah N, Ibrahim N, Aina Emran N, et al.

Pathol Res Pract, 2010 Apr 15;206(4):223-8.
PMID: 20097481 DOI: 10.1016/j.prp.2009.11.006

Genomic and transcriptomic alterations that affect cellular processes, such as cell proliferation, differentiation, apoptosis and invasion, commonly occur in breast oncogenesis. Epidemiological evidence has proven that the risk of breast cancer predisposition varies among different ethnicities. This study aims to identify the transcriptome changes that commonly occur during the transition of normal breast epithelium to carcinoma in three local ethnic groups (Malays, Chinese and Indians). The gene expression patterns of 43 breast carcinomas with 43 patient-matched normal breast tissues were investigated using Affymetrix U133A GeneChip (containing 22,283 probe sets targeting approximately 18,400 different transcripts) and analyzed with GeneSpring GX10. Our findings revealed a total of 33 significantly differentially expressed genes, which showed>2-fold change at a 99.9% confidence interval level (p<0.001). The significantly differentially expressed genes included CD24, CD36, CD9, TACSTD1, TACSTD2, HBB, LEP, LPL, AKR1C1, AKR1C2 and AKR1C3. Our results indicate that the vast majority of gene expression changes, from normal breast epithelial to carcinoma, found in our three major ethnic populations are similar to those in the Caucasian population. Further study of the differentially expressed genes identified in our present study is needed to search for potential breast tumor biomarkers. This will eventually help to improve the therapeutic and treatment strategies for breast cancer patients in the future.
Fluorescence in situ hybridization analysis using PAX8- and PPARG-specific probes reveals the presence of PAX8-PPARG translocation and 3p25 aneusomy in follicular thyroid neoplasms

Chia WK, Sharifah NA, Reena RM, Zubaidah Z, Clarence-Ko CH, Rohaizak M, et al.

Cancer Genet. Cytogenet., 2010 Jan 1;196(1):7-13.
PMID: 19963130 DOI: 10.1016/j.cancergencyto.2009.08.001

At the present time, the differentiation between follicular thyroid carcinoma (FTC) and adenoma can be made only postoperatively and is based on the presence of capsular or vascular invasion. The ability to differentiate preoperatively between the malignant and benign forms of follicular thyroid tumors assumes greater importance in any clinical setting. The PAX8-PPARG translocation has been reported to occur in the majority of FTC. In this study, a group of 60 follicular thyroid neoplasms [18 FTC, 1 Hurthle cell carcinoma (HCC), 24 follicular thyroid adenomas (FTA), 5 Hurthle cell adenomas (HCA), and 12 follicular variants of papillary thyroid carcinomas (FV-PTC)] were analyzed to determine the prevalence of the PAX8-PPARG translocation by fluorescence in situ hybridization. The PAX8-PPARG translocation was detected in 2/18 FTC (11.1%). In addition, 2/18 (11.1%) FTC and 1/5 (20%) HCA showed 3p25 aneusomy only. The frequency of the translocation detected in the study was lower compared to the earlier studies conducted in Western countries. This might be attributed to the ethnic background and geographic location. Detection of either the PAX8-PPARG translocation or the 3p25 aneusomy in FTC indicates that these are independent genetic events. It is hereby concluded that 3p25 aneusomy or PAX8-PPARG translocation may play an important role in the molecular pathogenesis of follicular thyroid tumors.
Fulltext Cri-du-chat syndrome: application of array cgh in diagnostic evaluation

Juriza, I., Sharifah Azween, S.O., Azli, I., Zarina, A.L., Mohd Fadly, M.A., Zubaidah, Z., et al.

Medicine & Health, 2010;5(2):108-113.
MyJurnal

The human genome contains many submicroscopic copy number variations which includes deletions, duplications and insertions. Although conventional karyotyping remains an important diagnostic tool in evaluating a dysmorphic patient with mental retardation, molecular diagnostic technology such as array comparative genomic hybridization (aCGH) has proven to be sensitive and reliable in detecting these submicroscopic anomalies. A 3 month-old infant with dysmorphic facies, microcephaly and global developmental delay was referred for genetic evaluation. Preliminary karyotyping which was confounded by the quality of metaphase spread was normal; however, aCGH detected a 30.6Mb deletion from 5p15.33-p13.3. This case illustrates the usefulness of aCGH as an adjunctive investigative tool for detecting chromosomal imbalances.

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