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  1. 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.
    Matched MeSH terms: Breast/metabolism*; Carcinoma, Ductal, Breast/metabolism
  2. Comparison of telomere length and telomerase activation between breast fibroadenoma and infiltrating ductal carcinoma in Malaysian women
    Looi LM, Cheah PL, Ng MH, Yip CH, Mun KS, Rahman NA
    Asian Pac J Cancer Prev, 2010;11(3):713-6.
    PMID: 21039041
    A study was initiated to explore possible differences in handling telomere attrition in the most common lignant and benign tumours of the breast in Malaysian women. Infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) represented the malignant and benign prototypes respectively. 29 IDC, 28 FA and 22 benign non-lesional control (BNL) breast tissue samples were analysed for telomerase activation using a Telomerase PCR ELISA kit (Boehringer Mannheim). In addition, 23 IDC, 12 FA and 14 BNL were subjected to telomere length determination with a TeloTAGGG Telomere Length Assay Kit (Roche Diagnostic GmbH, Germany), following digestion of genomic DNA by frequently cutting restriction enzymes RsaI and HinfI. Mean telomerase activity in IDC (A450nm=0.3338), but not FA (A450nm=0.0003) was significantly raised (p<0.05) compared with BNL (A450nm=0.0031). Similarly IDC (1.2 kb), but not FA (2.2 kb), showed significant telomere shortening (p<0.05) relative to BNL (2.9 kb). The findings imply that telomere attrition and telomerase activation differ between malignant and benign tumours of the breast and may be important for targeted therapy.
    Matched MeSH terms: Breast/metabolism; Carcinoma, Ductal, Breast/metabolism
  3. Fulltext Isolation, identification and quantification of differentially expressed proteins from cancerous and normal breast tissues
    Othman MI, Majid MI, Singh M, Man CN, Lay-Harn G
    Ann. Clin. Biochem., 2008 May;45(Pt 3):299-306.
    PMID: 18482919 DOI: 10.1258/acb.2007.007104
    Infiltrating ductal carcinoma (IDCA) is the most common type of breast cancer accounting for 85% of all invasive breast cancers.
    Matched MeSH terms: Breast/metabolism*; Carcinoma, Ductal, Breast/metabolism
  4. Genetic variations in transcription factor 7-like 2 (TCF7L2) gene: association of TCF7L2 rs12255372(G/T) or rs7903146(C/T) with breast cancer risk and clinico-pathological parameters
    Naidu R, Yip CH, Taib NA
    Med Oncol, 2012 Jun;29(2):411-7.
    PMID: 21301999 DOI: 10.1007/s12032-011-9837-8
    The purpose of the present study was to evaluate the association between TCF7L2 rs12255372(G/T) or rs7903146(C/T) polymorphism and breast cancer risk, and clinico-pathologic characteristics of the patients. Genotyping of these polymorphisms was performed on 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Malaysian population. The allele (P = 0.033) frequency of rs7903146 (T) polymorphism was significantly higher in the cancer patients than normal individuals. No significant association was demonstrated between CT (OR(adj) = 1.386; 95% CI, 0.985-1.949) or TT (OR(adj) = 1.579; 95% CI, 0.869-2.870) genotype and breast cancer risk. However, women who were carriers of T allele (OR(adj) = 1.316; 95% CI, 1.022-1.695) or T allele genotype (OR(adj) = 1.419; 95% CI, 1.027-1.960) showed significant increased risk of breast cancer. Women who were GT heterozygotes (OR(adj) = 1.329; 95% CI, 0.948-1.862) or TT homozygotes (OR(adj) = 1.574; 95% CI, 0.829-2.987), and carriers of T allele genotype (OR(adj) = 1.365; 95% CI, 0.989-1.883) or T allele (OR(adj) = 1.284; 95% CI, 0.995-1.657) were not associated with breast cancer risk. The rs7903146(T) allele genotype was significantly associated with nodal involvement (P = 0.003) but rs12255372 (T) allele genotype was not associated with the clinico-pathologic characteristics. In conclusion, our findings suggest that rs7903146 (T) variant may elevate the risk of breast cancer, thus could be a potential candidate for breast cancer susceptibility. The variant may also increase the metastatic potential of the tumor.
    Matched MeSH terms: Breast/metabolism*; Carcinoma, Ductal, Breast/metabolism
  5. Fulltext Comparison of protein expression profiles of different stages of lymph nodes metastasis in breast cancer
    Lee HH, Lim CA, Cheong YT, Singh M, Gam LH
    Int J Biol Sci, 2012;8(3):353-62.
    PMID: 22393307 DOI: 10.7150/ijbs.3157
    Breast cancer is the most common cancer among women worldwide. Breast cancer metastasis primarily happens through lymphatic system, where the extent of lymph node metastasis is the major factor influencing staging, prognosis and therapeutic decision of the disease. We aimed to study the protein expression changes in different N (regional lymph nodes) stages of breast cancer. Protein expression profiles of breast cancerous and adjacent normal tissues were mapped by proteomics approach that comprises of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and tandem mass spectrometry (LC-MS/MS) analysis. Calreticulin and tropomyosin alpha 3 chains were the common up-regulated proteins in N0, N1 and N2 stages of breast cancer. Potential biomarker for each N stage was HSP 70 for N0, 80 k protein H precursor and PDI for N1 stage while 78 kDa glucose-regulated protein was found useful for N2 stage. In addition, significant up-regulation of PDI A3 was detected only in the metastasized breast cancer. The up-regulation expression of these proteins in cancerous tissues can potentially use as indicators for diagnosis, treatment and prognosis of different N stages of breast cancer.
    Matched MeSH terms: Breast/metabolism; Carcinoma, Ductal, Breast/metabolism
  6. Proteomics of Grade 3 infiltrating ductal carcinoma in Malaysian Chinese breast cancer patients
    Othman MI, Majid MI, Singh M, Subathra S, Seng L, Gam LH
    Biotechnol Appl Biochem, 2009 Mar;52(Pt 3):209-19.
    PMID: 18564057 DOI: 10.1042/BA20070271
    Breast cancer is the leading cause of cancer-related mortality and morbidity among women worldwide and IDC (infiltrating ductal carcinoma) is the most common type of invasive breast cancer. The changes in the biological behaviour of cancer tissue can be predicted by measuring the differential protein expression of normal and cancerous tissues. Using a combination of SDS/PAGE and LC (liquid chromatography)-MS/MS (tandem MS), we identified 82 common and differentially expressed proteins from normal and cancerous breast tissues in 20 Malaysian Chinese patients with IDC. These proteins are extracted from the normal and cancerous tissue of patients and therefore represent the actual proteins involved in cancer development. Proteins identified possibly have significant roles in the development of breast cancer in Malaysian Chinese patients in view of their consistent expression in most of the patients, although some of the proteins had not been detected in earlier studies that were mostly carried out in Western countries. This observation suggests that molecular mechanisms leading to breast cancer development in this region may not be identical with those leading to IDC in Western regions.
    Matched MeSH terms: Carcinoma, Ductal, Breast/metabolism*
  7. C-erbB-2 oncoprotein amplification in infiltrating ductal carcinoma of breast relates to high histological grade and loss of oestrogen receptor protein
    Looi LM, Cheah PL
    Malays J Pathol, 1998 Jun;20(1):19-23.
    PMID: 10879259
    Eighty-six infiltrating ductal carcinoma of breast were studied by the standard avidin-biotin complex immunoperoxidase method on formalin-fixed, paraffin-embedded tissue sections, for oestrogen receptor (ER) protein and c-erbB-2 oncoprotein expression. They were categorized according to the modified Bloom and Richardson criteria into three histological grades. 21% tumours were ER positive while 44% were c-erbB-2 positive. Of ER positive tumours, 33.3% were c-erbB-2 positive whereas the c-erbB-2 positivity rate was much higher (47.1%) in ER negative tumours. Only 16% of c-erbB-2 positive tumours were ER positive while 25% of c-erbB-2 negative tumours were ER positive. This negative relationship between ER and c-erbB-2 expression was statistically significant (Mc Nemar's test, p < 0.005). The ER positivity rate did not vary significantly with histological grade. However, c-erbB-2 overexpression was significantly more prevalent in grade III tumours compared with grade I and II tumours (Chi-square test, p < 0.005). Since the c-erbB-2 oncogene has extensive structural homology to the epidermal growth factor receptor (EGFR) gene, we expect that c-erbB-2 oncoprotein would share functional similarities with EGFR leading to both loss of oestrogen receptor and poor prognosis in breast cancer. Its overexpression can be expected to relate to more aggressive tumour proliferation and may explain its correlation with high histological grade, a known indicator of aggressive cancer behaviour. As there is no indication that ER protein activity contributes to advancement in histological grade, it would appear that cellular dedifferentiation precedes ER loss during malignant transformation. It has been mooted that ER positive breast cancers which also show c-erbB-2 oncoprotein overexpression have a poorer response to hormonal therapy. The use of this parameter in the routine assessment of breast cancer patients may identify subsets of patients for more aggressive therapy.
    Matched MeSH terms: Carcinoma, Ductal, Breast/metabolism*
  8. Correlation between histological grade and c-erbB2 oncoprotein overexpression in infiltrating ductal carcinoma of breast
    Looi LM, Cheah PL, Yap SF
    Malays J Pathol, 1997 Jun;19(1):35-9.
    PMID: 10879240
    One hundred and twelve infiltrating ductal carcinoma of breast were studied by the standard avidinbiotin complex immunoperoxidase method on formalin-fixed, paraffin-embedded tissue sections, using a monoclonal antibody to c-erbB-2 oncoprotein. The same tumours were assessed and scored according to the Bloom and Richardson criteria into three histological grades. The distribution of tumours according to grade were: 8 Grade I, 34 Grade II and 70 Grade III. Forty-three (38.4%) tumours showed positive membrane staining for c-erbB-2 oncoprotein. These comprised 7 Grade II and 36 Grade III tumours with c-erbB-2 immunopositivity rates of 20.6% and 51.4% respectively. The oncoprotein was not expressed by Grade I tumours. This study shows a good correlation between c-erbB-2 expression and histological grade, a known prognostic indicator of invasive breast carcinoma. Because the c-erbB-2 oncogene has extensive structural homology to the epidermal growth factor receptor gene, its overexpression can be expected to result in more aggressive tumour behaviour. While it may be regarded as another indicator of poor prognosis breast cancers, its value in the selection of carcinomas less responsive to hormonal therapy and those more suitable for immunotherapy than chemotherapy has been mooted but remains to be clarified.
    Matched MeSH terms: Carcinoma, Ductal, Breast/metabolism*
  9. Fulltext The PCA and LDA analysis on the differential expression of proteins in breast cancer
    Liang S, Singh M, Dharmaraj S, Gam LH
    Dis Markers, 2010;29(5):231-42.
    PMID: 21206008 DOI: 10.3233/DMA-2010-0753
    Breast cancer is a leading cause of mortality in women. In Malaysia, it is the most common cancer to affect women. The most common form of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was undertaken to identify protein profile changes between cancerous and normal breast tissues from 18 patients. Two protein extracts; aqueous soluble and membrane associated protein extracts were studied. Thirty four differentially expressed proteins were identified. The intensities of the proteins were used as variables in PCA and reduced data of six principal components (PC) were subjected to LDA in order to evaluate the potential of these proteins as collective biomarkers for breast cancer. The protein intensities of SEC13-like 1 (isoform b) and calreticulin contributed the most to the first PC while the protein intensities of fibrinogen beta chain precursor and ATP synthase D chain contributed the most to the second PC. Transthyretin precursor and apolipoprotein A-1 precursor contributed the most to the third PC. The results of LDA indicated good classification of samples into normal and cancerous types when the first 6 PCs were used as the variables. The percentage of correct classification was 91.7% for the originally grouped tissue samples and 88.9% for cross-validated samples.
    Matched MeSH terms: Carcinoma, Ductal, Breast/metabolism*
  10. Fulltext The differential expression of aqueous soluble proteins in breast normal and cancerous tissues in relation to ethnicity of the patients; Chinese, Malay and Indian
    Liang S, Singh M, Gam LH
    Dis Markers, 2010;28(3):149-65.
    PMID: 20534901 DOI: 10.3233/DMA-2010-0694
    Female breast cancer is one of the leading causes of female mortality worldwide. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of the women in Malaysia, the Chinese have the highest number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was applied in this study to identify changes in the protein profile of cancerous tissues compared with normal tissues from 18 patients; 8 Chinese, 6 Malay and 4 Indian were analysed. Twenty-four differentially expressed hydrophilic proteins were identified. We evaluated the potential of these proteins as biomarkers for infiltrating ductal carcinoma based on their ethnic-specific expressions. Three of the upregulated proteins, calreticulin, 14-3-3 protein zeta and 14-3-3 protein eta, were found to be expressed at a significantly higher level in the cancerous breast tissues when compared with the normal tissues in cases of infiltrating ductal carcinoma. The upregulation in expression was particularly dominant in the Malay cohort.
    Matched MeSH terms: Breast/metabolism*
  11. HLA-A and breast cancer in West Peninsular Malaysia
    Leong PP, Muhammad R, Ibrahim N, Cheong SK, Seow HF
    Med Oncol, 2011 Mar;28(1):51-6.
    PMID: 20069393 DOI: 10.1007/s12032-009-9414-6
    Breast cancer is the most common malignancy among females in Malaysia. Attempts have been made to investigate the association between breast cancer and human leukocyte antigen (HLA) types. However, data from those previous studies are highly variable. The aim of this study is to investigate the association between HLA-A types and clinicopathological factors in breast cancer. The frequencies of HLA-A type in 59 female patients with infiltrating ductal of the breast were determined by polymerase chain reaction method. HLA-A2/A30 and A2/A31 haplotype (5.1%; P = 0.045) as well as HLA-A30 (5.1%, P = 0.045) and A31 (6.8%; P = 0.020) allele were significant higher in the patients than controls (0%). HLA-A24 allele was negatively related to lymph node metastasis (r = -0.316; P = 0.021) whereas, A26 (r = -0.430; P = 0.001) and A36 (r = -0.430; P = 0.001) alleles were negatively correlated to distant metastasis in breast cancer. Negative correlations between HLA-A26/A36 (r = -0.430; P = 0.001), A2/A11 (r = -0.276; P = 0.044), A24/A34 (r = -0.430; P = 0.001) haplotypes and distant metastasis were identified. Interestingly, Her2 expression in breast carcinoma was negatively correlated to A11/24 haplotypes (r = -0.294; P = 0.034) but positively correlated to homozygous HLA-A24 (r = 0.396; P = 0.040). In conclusion, HLA-A2, -A30 and A31 were associated with breast cancer.
    Matched MeSH terms: Carcinoma, Ductal, Breast/metabolism*
  12. Fulltext The differential expression of aqueous soluble proteins in breast normal and cancerous tissues in relation to stage and grade of patients
    Liang S, Singh M, Gam LH
    J Biomed Biotechnol, 2010;2010:516469.
    PMID: 21197096 DOI: 10.1155/2010/516469
    Breast cancer is a leading cause of female deaths worldwide. In Malaysia, it is the most common form of female cancer while Infiltrating ductal carcinoma (IDC) is the most common form of breast cancer. A proteomic approach was used to identify changes in the protein profile of breast cancerous and normal tissues. The patients were divided into different cohorts according to tumour stage and grade. We identified twenty-four differentially expressed hydrophilic proteins. A few proteins were found significantly related to various stages and grades of IDC, amongst which were SEC13-like 1 (isoform b), calreticulin, 14-3-3 protein zeta, and 14-3-3 protein eta. In this study, we found that by defining the expression of the proteins according to stages and grades of IDC, a significant relationship between the expression of the proteins with the stage or grade of IDC can be established, which increases the usefulness of these proteins as biomarkers for IDC.
    Matched MeSH terms: Breast/metabolism
  13. Fulltext Estrogen receptor-negative breast ductal carcinoma: clinicopathological features and MIB-1 (Ki-67) proliferative index association
    Mdpaiman N, Md Ali SA, Mdzin R, Meor Kamal MZ, Md Amin WA, Nallusamy M, et al.
    PLoS One, 2014;9(2):e89172.
    PMID: 24586570 DOI: 10.1371/journal.pone.0089172
    Breast cancer estrogen receptor (ER) status is one of the strong additional factors in predicting response of patients towards hormonal treatment. The main aim of this study was to assess the morphological characteristics and proliferative activity using MIB-1(Ki-67) of estrogen receptor negative invasive breast ductal carcinoma (NOS type) as well as to correlate these features with clinicopathological data. We also aim to study the expression of c-erbB2 in ER negative breast tumors. High proliferative rate (MIB-1 above 20%) was observed in 63 (63.6%) of 99 ER negative tumors and that these tumors were associated with high expression of c-erbB2 (57.6%). We observed that MIB-1 is a reliable independent prognostic indicator for ER negative infiltrating ductal carcinoma in this study.
    Matched MeSH terms: Carcinoma, Ductal, Breast/metabolism*
  14. 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.

    Matched MeSH terms: Breast/metabolism*
  15. The estrogen receptor negative-progesterone receptor positive breast carcinoma is a biological entity and not a technical artifact
    Ng CH, Pathy NB, Taib NA, Mun KS, Rhodes A, Yip CH
    Asian Pac J Cancer Prev, 2012;13(4):1111-3.
    PMID: 22799290
    The ER-/PR+ breast tumor may be the result of a false ER negative result. The aim of this study was to investigate whether there is a difference in patient and tumor characteristics of the ER-/PR+ phenotype in an Asian setting. A total of 2629 breast cancer patients were categorized on the basis of their age, ethnicity, tumor hormonal receptor phenotype, grade and histological type. There were 1230 (46.8%) ER+/PR+, 306 (11.6%) ER+/PR-, 122 (4.6%) ER-/PR+ and 972 (37%) ER-/PR-. ER-/PR+ tumors were 2.5 times more likely to be younger than 50 years at diagnosis (OR: 2.52; 95% CI: 1.72-3.67). Compared to ER+/PR+ tumors, the ER-/ PR+ phenotype was twice more likely to be associated with grade 3 tumors (OR:2.02; 95%CI: 1.00-4.10). In contrast, compared to ER-/PR- tumors, the ER-/PR+ phenotype was 90% less likely to be associated with a grade 3 tumor (OR: 0.12; 95%CI:0.05-0.26), and more likely to have invasive lobular than invasive ductal histology (OR: 3.66; 95%CI: 1.47-9.11). These results show that the ER-/PR+ phenotype occurs in a younger age group and is associated with intermediate histopathological characteristics compared to ER+/PR+ and ER-/PR- tumors. This may imply that it is a distinct entity and not a technical artifact.
    Matched MeSH terms: Carcinoma, Ductal, Breast/metabolism*
  16. Immunohistochemical expression of vascular endothelial growth factor (VEGF) and p53 in breast lesions
    Noranizah W, Siti-Aishah MA, Munirah MA, Norazlin MH, Rohaizak M, Naqiyah I, et al.
    Clin Ter, 2010;161(2):129-37.
    PMID: 20499026
    Vascular endothelial growth factor (VEGF) is a leading factor for tumour angiogenesis and p53 protein is the product of a tumor suppressor gene. The main aim of the study was to assess the association of p53 protein with VEGF expression in breast carcinoma.
    Matched MeSH terms: Breast/metabolism*
  17. Potential hydrophobic protein markers of breast cancer in Malaysian Chinese, Malay and Indian patients
    Liang S, Singh M, Gam LH
    Cancer Biomark, 2010;8(6):319-30.
    PMID: 22072120 DOI: 10.3233/CBM-2011-0221
    Breast cancer is a leading cause of worldwide mortality in females. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of these, the Chinese had the most number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was used to identify protein profile changes in cancerous tissues compared with the normal tissues, the tissues were collected from patients of three different ethnicities, i.e. Chinese, Malay and Indian. Ten differentially expressed hydrophobic proteins were identified. We had evaluated the potential of these proteins as biomarker for infiltrating ducal carcinoma (IDC) and the ethnic-specific expression of these proteins was also determined. The data showed that peroxiredoxin-2, heat shock protein 60, protein disulfide isomerase and calreticulin may serve as ethnic-related potential markers for either one or combination of Chinese, Malay and Indian cohorts as their expression levels were significantly high in the cancerous tissues compared to the normal tissues in the ethnic group tested.
    Publication year=2010-2011
    Matched MeSH terms: Carcinoma, Ductal, Breast/metabolism*
  18. Fulltext Clinical characteristics of triple-negative breast cancer: experience in an Asian developing country
    Tan GH, Taib NA, Choo WY, Teo SH, Yip CH
    Asian Pac J Cancer Prev, 2009 Jul-Sep;10(3):395-8.
    PMID: 19640180
    INTRODUCTION: Triple negative (TN) breast cancers are defined by a lack of expression of oestrogen, progesterone, and HER2 receptors. They tend to have a higher grade, with a poorer outcome compared to non-TN breast cancers.
    OBJECTIVE: The aim of this study is to determine the incidence of TN breast cancer in an Asian country consisting of Malays, Chinese and Indians, and to determine the factors associated with this type of breast cancer.
    RESULTS: The incidence of TN breast cancer in the University Malaya Medical Center is 17.6%. There is no significant difference amongst the Malays, Chinese and Indians. In bivariate analysis, TN breast cancer was significantly associated with younger age and Grade 3. However, in multivariate analysis using logistic regression, TN breast cancer was only associated with Grade 3.
    CONCLUSION: The incidence of TN breast cancer in our study is similar to other studies, and associated with a higher grade.
    Study site: University Malaya Medical Centre (UMMC)
    Matched MeSH terms: Carcinoma, Ductal, Breast/metabolism
  19. Subcellular localization of leptin and leptin receptor in breast cancer detected in an electron microscopic study
    Al-Shibli SM, Amjad NM, Al-Kubaisi MK, Mizan S
    Biochem Biophys Res Commun, 2017 Jan 22;482(4):1102-1106.
    PMID: 27914811 DOI: 10.1016/j.bbrc.2016.11.165
    Leptin (LEP) and leptin receptor (LEPR) have long been found associated with breast cancer. So far no high-resolution method such as electron microscopy has been used to investigate the subcellular localization of leptin and leptin receptor in breast cancer. We collected cancer and non-cancer breast tissues from 51 women with invasive ductal breast cancer. Leptin and leptin receptor in the tissues were estimated using immunohistochemistry (IHC). LEP and LEPR were localized at subcellular level by immunocytochemistry (ICC) using ultra-fine gold particle conjugated antibody, and visualized with transmission electron microscopy (TEM). IHC showed high presence of LEP and LEPR in 65% and 67% respectively of the breast cancer samples, 100% and 0% respectively of the adipose tissue samples, and no high presence in the non-cancer breast tissue samples. On TEM views both LEP and LEPR were found highly concentrated within the nucleus of the cancer cells, indicating that nucleus is the principal seat of action. However, presence of high concentration of LEP does not necessarily prove its over-expression, as often concluded, because LEP could be internalized from outside by LEPR in the cells. In contrast, LEPR is definitely over-expressed in the ductal breast cancer cells. Therefore, we hypothesize that over-expression of LEPR, rather than that of LEP has a fundamental role in breast carcinogenesis in particular, and probably for LEP-LEPR associated tumors in general.
    Matched MeSH terms: Carcinoma, Ductal, Breast/metabolism
  20. Fulltext Expression of survivin and its clinicopathological correlations in invasive ductal carcinoma of the breast
    Al-Joudi FS, Iskandar ZA, Hasnan J, Rusli J, Kamal Y, Imran AK, et al.
    Singapore Med J, 2007 Jul;48(7):607-14.
    PMID: 17609820
    INTRODUCTION: Survivin is a 16.5-kDa intracellular protein that inhibits apoptosis and regulates cell division, and belongs to the inhibitors of apoptosis gene family. It appears to have an important role in regulating apoptosis at the cell cycle checkpoints. Survivin has been found to have a differential distribution in cancer compared to normal tissue, as it is over-expressed in malignant tumours.
    METHODS: In addition to the demographical analysis of the disease, data from 382 women with invasive ductal carcinoma of the breast were collected from three hospitals in Northeast Malaysia, and analysed for survivin expression by immunohistochemistry.
    RESULTS: Invasive ductal carcinoma of the breast was found to be the most prevalent breast cancer type. Survivin was detected in 260 (68.1 percent) study cases. In addition, significant correlations have been shown between survivin expression on one hand, and tumour size and lymph node involvement on the other hand (p-value is less than 0.05). However, no significant correlations were found with other clinicopathological factors, such as tumour histological grade, tumour side, oestrogen and progesterone receptors. Nuclear expression of survivin was detected in 16.5 percent of the study cases, cytoplasmic expression was detected in 24.1 percent, and 27.5 percent of the cases expressed survivin in both nuclear and cytoplasmic locations simultaneously. The subcellular localisation of survivin was significantly correlated (p is less than 0.001) with the lymph node involvement indicating its value in predicting the aggressiveness of tumour cells, since it increases the resistance to apoptosis and promotes cell proliferation.
    CONCLUSION: This is the fi rst known report on survivin expression in cancer in West Malaysia and Southeast Asia. It emphasises the importance of the detection of survivin in breast cancer to aid in diagnosis, confirm malignancy, and to assess the disease progress and response to therapy.
    Matched MeSH terms: Carcinoma, Ductal, Breast/metabolism*
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