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Correlations in survivin expression with the expression of p53 and bcl-2 in invasive ductal carcinoma of the breast

Al-Joudi FS, Iskandar ZA, Imran AK

Southeast Asian J. Trop. Med. Public Health, 2007 Sep;38(5):904-10.
PMID: 18041310

This work studied the correlations between survivin, bcl-2 and p53 in infiltrating ductal carcinoma of the breast. A total number of 382 cases were collected from 3 hospitals in northeastern Malaysia. Survivin, bcl-2 and p53 were detected by immunohistochemistry on samples prepared from tissue blocks. Significant correlations were found between tumor histological grades and tumor size and lymph node involvement. Highly significant statistical correlations (p<0.001) were found in expression of the markers under study. It is concluded that such significant correlations may imply that the alterations in the expression take place in a concerted fashion, implying that many of these cases may share common abnormalities.

Matched MeSH terms: Carcinoma, Ductal, Breast/genetics; Carcinoma, Ductal, Breast/metabolism*; Carcinoma, Ductal, Breast/pathology
Breast cancer in Sabah, Malaysia: a two year prospective study

Leong BD, Chuah JA, Kumar VM, Yip CH

Asian Pac J Cancer Prev, 2007 Oct-Dec;8(4):525-9.
PMID: 18260722

INTRODUCTION: Malaysian women have a 1 in 20 chance of developing breast cancer in their lifetime. Sabah, formerly known as North Borneo, is part of East Malaysia with a population of 3.39 million and more than 30 ethnic groups. We conducted a 2 year prospective epidemiological study to provide unreported data of breast cancer from this part of the world and to recognise which particular group of patients are more likely to present with advanced disease.

METHODS: All newly diagnosed breast cancers seen at the Queen Elizabeth Hospital, Kota Kinabalu, from January 2005 to December 2006 were included in the study. Patient and tumour characteristics, including age, race, education, socioeconomic background, parity, practice of breast feeding, hormonal medication intake, menopausal status, family history, mode of presentation, histology, grade, stage of disease and hormonal receptors status were collected and analysed.

RESULTS: A total of 186 patients were seen. The commonest age group was 40 to 49 years old (32.3%). Chinese was the commonest race (30.6%) followed by Kadazan-Dusun (24.2%). The commonest histology was invasive ductal carcinoma (88.4%). Stages at presentation were Stage 0- 4.8%, Stage I- 12.9%, Stage II- 30.1%, Stage III- 36.6% and Stage IV- 15.6%. The estrogen and progesterone receptor status was positive in 59.1% and 54.8% of cases, respectively. 73.7% of Chinese patients presented with early cancer compared to 36.4% of the other races. Patients who presented with advanced disease were also poor, non-educated and from rural areas. 20.4% of patients defaulted treatment; most of them opted for traditional alternatives.

CONCLUSIONS: Sabahan women with breast cancer present late. Great efforts are needed to improve public awareness of breast cancer, especially among those who have higher risk of presenting with advanced disease.

Matched MeSH terms: Carcinoma, Ductal, Breast/epidemiology; Carcinoma, Ductal, Breast/pathology
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: Carcinoma, Ductal, Breast/diagnosis*; Carcinoma, Ductal, Breast/metabolism
Fine needle aspiration cytology of neuroendocrine carcinoma of the breast--a case report and review of literature

Kadir AA, Iyengar KR, Peh SC, Yip CH

Malays J Pathol, 2008 Jun;30(1):57-61.
PMID: 19108413

Neuroendocrine carcinomas of the breast are uncommon tumors known to occur in the elderly. While focal neuroendocrine differentiation may be noted in many ductal and lobular carcinomas, the term neuroendocrine carcinoma is to be applied when more than 50% of the tumor shows such differentiation. This case report details the cytological features of a neuroendocrine carcinoma that was encountered in our hospital. The fine needle aspiration (FNA) smears showed discohesive polygonal cells with abundant cytoplasm, many of which contained eosinophilic granules located at one pole. Histology of the mastectomy and axillary lymph nodes specimen from this patient showed features of neuroendocrine carcinoma--solid type, with metastasis, confirmed with immunohistochemistry. The patient is disease free seven months after surgery. This case highlights the need to closely observe cytological details to identify this rare tumor that may otherwise appear to be invasive duct carcinoma--not otherwise specified on FNA. The implications of diagnosing neuroendocrine differentiation for prognosis and management are also discussed.

Matched MeSH terms: Carcinoma, Ductal, Breast/pathology
Fulltext The expression of p53 in invasive ductal carcinoma of the breast: a study in the North-East States of Malaysia

Al-Joudi FS, Iskandar ZA, Rusli J

Med J Malaysia, 2008 Jun;63(2):96-9.
PMID: 18942291

The p53 gene is a tumour suppressor gene that encodes a 393-amino-acid nuclear DNA-binding phosphoprotein. The significance of p53 detection is that p53 mutation is linked with chemo-resistance and transformation to more aggressive disease in a large number of tumour types and it was confirmed that mutant p53 is involved in neoplastic transformations. In addition, the expression of p53 has been closely correlated with clinicopathological findings. Since breast cancer has been reported as one of the most frequent malignancies in women in Malaysia, the expression of p53 was studied in 382 cases of invasive ductal carcinoma of the breast, obtained from three major hospitals in the North-East States of Malaysia. The study utilized an enzyme immunohistochemistry assay for the detection of p53. It was found that p53 was expressed in 29.6% of all the study cases. Furthermore, its expression was significantly correlated with the age and the clinical grading of the disease. No significant statistical correlations were depicted with lymph node status, tumour size, side of tumour, and expression of estrogen and progesterone receptors. Nevertheless, knowledge of the p53 status may be valuable in making clinical decisions regarding diagnosis, prognosis and therapy.

Matched MeSH terms: Carcinoma, Ductal, Breast/genetics*
Minichromosome maintenance protein 2 is a reliable proliferative marker in breast carcinoma

Reena RM, Mastura M, Siti-Aishah MA, Munirah MA, Norlia A, Naqiyah I, et al.

Ann Diagn Pathol, 2008 Oct;12(5):340-3.
PMID: 18774496 DOI: 10.1016/j.anndiagpath.2008.04.001

This is a study aimed to examine the distribution pattern of a specific minichromosome maintenance protein 2 (MCM2) in benign and malignant breast tissue. We also aim to correlate the frequency of expression of MCM2 with the degree of tumor differentiation. We used immunohistochemistry to examine the distribution and expression pattern of MCM2 on formalin-fixed paraffin-embedded tissue sections of benign (n = 30) and malignant breast tissue (n = 70) (IDC 56, DCIS 4, ILC 2, nonductal 4, mixed type 4). We quantified MCM2 expression by calculating a labeling index, which represents the percentage of epithelial nuclei that stained positively. Immunoreactivity was heterogenous in all the 70 malignant cases examined. Epithelial cells in cycle are most frequent at the tumor periphery. Labeling index of MCM2 was greatest in grade 3 (poorly differentiated) and lowest in grade 1 tumors (well differentiated). Minichromosome maintenance protein 2 expression in breast cancer showed a positive association with histologic grade (P < .05). In all the benign breast tissue examined, no proliferating compartments could be characterized. Minichromosome maintenance protein 2 is a useful proliferative marker of breast carcinoma. The frequency of expression of MCM2 showed an inverse correlation with the degree of tumor differentiation.

Matched MeSH terms: Carcinoma, Ductal, Breast/metabolism; Carcinoma, Ductal, Breast/secondary
Fulltext E-cadherin expression correlates with histologic type but not tumour grade in invasive breast cancer

Nurismah MI, Noriah O, Suryati MY, Sharifah NA

Asian Pac J Cancer Prev, 2008 Oct-Dec;9(4):699-702.
PMID: 19256762

The traditional classification of infiltrating breast carcinomas into ductal and lobular can be diagnostically challenging in a small proportion of cases with equivocal histological features and in in-situ lesions with overlapping features. Distinguishing between the infiltrating ductal (IDC) and lobular (ILC) carcinomas is clinically important because of the different pattern of systemic metastases and prognostic evaluation. E-cadherin is a potentially useful immunohistochemical marker which may serve to differentiate between the two tumour types. We therefore studied E-cadherin expression in 32 cases of breast carcinomas comprising 16 IDCs and 16 ILCs. The correlation between E-cadherin expression and the histological grade of IDCs was also analysed. Our results showed complete loss of E-cadherin expression in all ILCs, while the IDCs consistently showed variable E-cadherin positivity. No significant correlation was found between E- cadherin expression and the histological grade of IDCs. We conclude from this study that E-cadherin is a useful marker to differentiate between IDC and ILC of the breast. A larger study of IDCs is now needed to further evaluate the correlation between E-cadherin and tumour grade to estimate its prognostic potential.

Matched MeSH terms: Carcinoma, Ductal, Breast/pathology*; Carcinoma, Ductal, Breast/chemistry*
Predictors of axillary lymph node metastases in breast cancer: is there a role for minimal axillary surgery?

Yip CH, Taib NA, Tan GH, Ng KL, Yoong BK, Choo WY

World J Surg, 2009 Jan;33(1):54-7.
PMID: 18958521 DOI: 10.1007/s00268-008-9782-7

Axillary nodal status is one of the most important prognostic factors in breast cancer. In the present study we used it to determine the predictors of axillary lymph node metastases in breast cancer and to determine if there is a group of patients in whom minimal axillary surgery is indicated.

Matched MeSH terms: Carcinoma, Ductal, Breast/ethnology; Carcinoma, Ductal, Breast/secondary*; Carcinoma, Ductal, Breast/surgery
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*
Factors associated with HER2 overexpression in breast cancer: Experience in an Asian developing country

Tan GH, Choo WY, Taib NA, Yip CH

Asian Pac J Cancer Prev, 2009;10(5):837-40.
PMID: 20104975

INTRODUCTION: The HER2 gene is amplified in up to 30% of human breast cancers, leading to overexpression of the HER2 protein on the cell surface. Overexpression of HER2 is associated with a more aggressive cancer and hence a poorer overall survival.
OBJECTIVE: To evaluate the association between clinico-pathological features and HER2 overexpression in breast cancer.
METHODS: This is a retrospective study conducted in the Department of Surgery, University Malaya Medical Centre. The association between HER2 overexpression, determined by immunohistochemistry, and other clinicopathological factors was evaluated in 996 patients with newly diagnosed breast cancer treated from 2005 to 2007 using univariate and multivariate logistic regression.
RESULTS: HER2 overexpression occurred in 30.3% of patients. On bivariate analysis, HER2 overexpression was inversely related to ER expression (p<0.01) and PR expression (p<0.01). This overexpression was associated with a higher tumour grade, lymphovascular positivity and infiltrating ductal carcinoma subtype. On multivariate analysis, HER2 overexpression was significantly associated with higher tumour grade (p= 0.018, CI 1.25-11.04), PR negativity (p= 0.002, CI 0.30-0.77) and lymphovascular positivity (p= 0.042, CI 1.01-2.12).
CONCLUSIONS: HER2 overexpression was observed in 30.3% of Malaysian female breast cancer patients. This group of patients represents a more aggressive subtype of breast cancer with higher tumour grade, PR negativity and lymphovascular positivity. No significant relationship was established between HER2 overexpression and age, race, lymph node, ER, pathology subtype and stage of disease from this study.

Matched MeSH terms: Carcinoma, Ductal, Breast/metabolism*; Carcinoma, Ductal, Breast/pathology
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; Carcinoma, Ductal, Breast/pathology*
Fulltext Immunohistochemical expression of MAP1LC3A and MAP1LC3B protein in breast carcinoma tissues

Othman EQ, Kaur G, Mutee AF, Muhammad TS, Tan ML

J Clin Lab Anal, 2009;23(4):249-58.
PMID: 19623642 DOI: 10.1002/jcla.20309

Autophagy is a protein degradation process within the cell and its deregulation has been linked to various diseases and the formation of cancer. One of the important proteins involved in the autophagy process is microtubule-associated protein 1 light chain 3 (MAP1LC3). The aims of this study were to determine the MAP1LC3A and MAP1LC3B protein expression in both normal and cancer breast tissues and to determine the relationship between the expression of these proteins and type of tissues. Immunohistochemistry assessments were carried out on tissue microarrays consisting of breast tissues. MAP1LC3A expression was detected in 52/56 of normal breast tissue cores and 65/67 of breast cancer tissue cores. MAP1LC3B expression was detected in 55/56 of normal breast tissue cores and 67/67 of breast cancer tissue cores. MAP1LC3A and MAP1LC3B protein are expressed in the majority of normal and cancer breast tissues. A large number of MAP1LC3A and MAP1LC3B positive breast cancer tissues cores have high proportion of stained cells (81-100%) as compared with normal breast tissues. However, a significantly higher number of breast cancer tissues were found to express the MAP1LC3A protein with strong immunoreactivity as compared with the normal tissues, suggesting that MAP1LC3A may play a role in breast cancer development.

Matched MeSH terms: Carcinoma, Ductal, Breast/metabolism; Carcinoma, Ductal, Breast/pathology
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: Carcinoma, Ductal, Breast/genetics*; Carcinoma, Ductal, Breast/metabolism; Carcinoma, Ductal, Breast/pathology
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.

Matched MeSH terms: Carcinoma, Ductal, Breast/genetics*; Carcinoma, Ductal, Breast/metabolism
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: Carcinoma, Ductal, Breast/genetics; Carcinoma, Ductal, Breast/metabolism; Carcinoma, Ductal, Breast/pathology*
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/ethnology; Carcinoma, Ductal, Breast/genetics; Carcinoma, Ductal, Breast/metabolism*
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*
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/genetics; Carcinoma, Ductal, Breast/metabolism*
Fulltext An analysis of predictive biomarkers in routine histopathological reporting of infiltrating ductal breast carcinoma in a tertiary hospital in Malaysia with a focus on limitations and directions for future development

Teoh KH, Looi LM, Sabaratnam S, Cheah PL, Nazarina AR, Mun KS

Malays J Pathol, 2011 Jun;33(1):35-42.
PMID: 21874750 MyJurnal

Predictive biomarkers such as oestrogen (ER) and progesterone (PR) receptors and c-erbB-2 oncoprotein have become a staple in breast cancer reports in the country as they increasingly play an important role in the treatment and prognosis of women with breast cancers. This study reviews the practice of histopathology reporting of these biomarkers in a Malaysian tertiary hospital setting. Retrospective data on demographic, pathological and biomarker profiles of patients with invasive ductal carcinoma who had undergone mastectomy or lumpectomy with axillary node clearance from 2005 to 2006 were retrieved from the Department of Pathology, Penang Hospital and analysed. The prevalence of ER positivity (55.8%), PR positivity (52.5%), c-erbB-2 oncoprotein overexpression (24%) and triple negativity (ER negative, PR negative, c-erbB-2 negative) (15%) by immunohistochemistry were comparable with other studies. Notably, c-erbB-2 overexpression was equivocal (2+) in 15% of cases. Since about a quarter of equivocal (2+) cases usually show amplification by FISH, a small but certain percentage of patients would miss the benefit of anti-c-erbB-2 antibody therapy if FISH is not performed. New ASCO/CAP guidelines on the quantitation of ER and PR will probably increase the prevalence of ER/PR positivity, invariably leading to significant ramifications on the management of patients as more patients would be deemed eligible for endocrine therapy, as well as categorisation of triple negative breast cancers.

Matched MeSH terms: Carcinoma, Ductal, Breast/diagnosis; Carcinoma, Ductal, Breast/genetics*
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: Carcinoma, Ductal, Breast/genetics*; Carcinoma, Ductal, Breast/metabolism; Carcinoma, Ductal, Breast/pathology*

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