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Fulltext Structural Studies of Epithelial Mesenchymal Transition Breast Tissues

Mohd Sobri SN, Abdul Sani SF, Sabtu SN, Looi LM, Chiew SF, Pathmanathan D, et al.

Sci Rep, 2020 02 06;10(1):1997.
PMID: 32029810 DOI: 10.1038/s41598-020-58932-5

At the supramolecular level, the proliferation of invasive ductal carcinoma through breast tissue is beyond the range of standard histopathology identification. Using synchrotron small angle x-ray scattering (SAXS) techniques, determining nanometer scale structural changes in breast tissue has been demonstrated to allow discrimination between different tissue types. From a total of 22 patients undergoing symptomatic investigations, different category breast tissue samples were obtained in use of surgically removed tissue, including non-lesional, benign and malignant tumour. Structural components of the tissues were examined at momentum transfer values between q = 0.2 nm-1 and 1.5 nm-1. From the SAXS patterns, axial d-spacing and diffuse scattering intensity were observed to provide the greatest discrimination between the various tissue types, specifically in regard to the epithelial mesenchymal transition (EMT) structural component in malignant tissue. In non-lesional tissue the axial period of collagen is within the range 63.6-63.7 nm (formalin fixed paraffin embedded (FFPE) dewaxed) and 63.4 (formalin fixed), being 0.9 nm smaller than in EMT cancer-invaded regions. The overall intensity of scattering from cancerous regions is a degree of magnitude greater in cancer-invaded regions. Present work has found that the d-spacing of the EMT positive breast cancer tissue (FFPE (dewaxed)) is within the range 64.5-64.7 nm corresponding to the 9th and 10th order peaks. Of particular note in regard to formalin fixation of samples is that no alteration is observed to occur in the relative differences in collagen d-spacing between non-lesional and malignant tissues. This is a matter of great importance given that preserved-sample and also retrospective study of samples is greatly facilitated by formalin fixation. Present results indicate that as aids in tissue diagnosis SAXS is capable of distinguishing areas of invasion by disease as well as delivering further information at the supramolecular level.

Matched MeSH terms: Carcinoma, Ductal, Breast/pathology*
Follow-up of B3 breast lesions without residual microcalcifications post vacuum-assisted biopsy, can contrast-enhanced digital mammography help?

Bicchierai G, Nori J, De Benedetto D, Boeri C, Vanzi E, Bianchi S, et al.

Breast J, 2020 02;26(2):299-302.
PMID: 31486197 DOI: 10.1111/tbj.13598
Matched MeSH terms: Carcinoma, Ductal, Breast/pathology
Single-nucleotide polymorphisms and mRNA expression of CYP1B1 influence treatment response in triple negative breast cancer patients undergoing chemotherapy

Abdul Aziz AA, Md Salleh MS, Mohamad I, Krishna Bhavaraju VM, Mazuwin Yahya M, Zakaria AD, et al.

J Genet, 2018 Dec;97(5):1185-1194.
PMID: 30555068

Triple negative breast cancer (TNBC) is typically associated with poor and interindividual variability in treatment response. Cytochrome P450 family 1 subfamily B1 (CYP1B1) is a metabolizing enzyme, involved in the biotransformation of xenobiotics and anticancer drugs. We hypothesized that, single-nucleotide polymorphisms (SNPs), CYP1B1 142 C>G, 4326 C>G and 4360 A>G, and CYP1B1 mRNA expression might be potential biomarkers for prediction of treatment response in TNBC patients. CYP1B1 SNPs genotyping (76 TNBC patients) was performed using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods and mRNA expression of CYP1B1 (41 formalin-fixed paraffin embeddedblocks) was quantified using quantitative reverse transcription PCR. Homozygous variant genotype (GG) and variant allele (G) of CYP1B1 4326C>G polymorphism showed significantly higher risk for development of resistance to chemotherapy with adjusted odds ratio (OR): 6.802 and 3.010, respectively. Whereas, CYP1B1 142 CG heterozygous genotype showed significant association with goodtreatment response with adjusted OR: 0.199. CYP1B1 142C-4326G haplotype was associated with higher risk for chemoresistance with OR: 2.579. Expression analysis revealed that the relative expression of CYP1B1 was downregulated (0.592) in cancerous tissue compared with normal adjacent tissues. When analysed for association with chemotherapy response, CYP1B1 expression was found to be significantly upregulated (3.256) in cancerous tissues of patients who did not respond as opposed to those of patients who showed response to chemotherapy. Our findings suggest that SNPs together with mRNA expression of CYP1B1 may be useful biomarkers to predict chemotherapy response in TNBC patients.

Matched MeSH terms: Carcinoma, Ductal, Breast/pathology
Incidence and prognosis of non-metastatic triple negative breast cancer (TNBC) among different races in Southeast Asia

Alcantara VS, Lim GH, Lim SH, Sultana R, Lee JA

J Surg Oncol, 2017 Apr;115(5):523-537.
PMID: 28168712 DOI: 10.1002/jso.24559

BACKGROUND AND OBJECTIVES: Triple negative breast cancer (TNBC) carries a worse prognosis compared to the other subtypes. There have been conflicting studies that race may impact the prognosis of TNBC patients. We aim to determine the incidence and prognosis of TNBC among the different ethnic races in Singapore, and to determine its associated risk factors for prognosis.
METHODS: Patients diagnosed with invasive breast cancer (BC) from 2005 to 2013 at our tertiary institution were included and divided according to race and subtypes. Demographic and clinical information of non-metastatic TNBC patients were analyzed. Log-rank test, univariate and multivariate Cox proportional hazard regression models were used to find associated risk factors related with overall survival (OS) and disease-free survival (DFS).
RESULTS: Among 1227 BC patients, 129 (10.5%) had TNBC. TNBC patients had the worst OS (P: 0.0005) and DFS (P: 0.0016) among the subtypes. However, variations in race did not have any difference in OS or DFS among TNBC patients. Axillary lymph node involvement, invasive lobular histology, larger tumor size, and the presence of lymphovascular invasion (LVI) were factors associated with both poor DFS and OS among TNBC patients.
CONCLUSIONS: Racial variation did not have any impact on the prognosis of the TNBC.

Matched MeSH terms: Carcinoma, Ductal, Breast/pathology
Fulltext Outcome after neoadjuvant chemotherapy in Asian breast cancer patients

Lim LY, Miao H, Lim JS, Lee SC, Bhoo-Pathy N, Yip CH, et al.

Cancer Med, 2017 Jan;6(1):173-185.
PMID: 28000426 DOI: 10.1002/cam4.985

We aim to identify clinicopathologic predictors for response to neoadjuvant chemotherapy and to evaluate the prognostic value of pathologic complete response (pCR) on survival in Asia. This study included 915 breast cancer patients who underwent neoadjuvant chemotherapy at five public hospitals in Singapore and Malaysia. pCR following neoadjuvant chemotherapy was defined as 1) no residual invasive tumor cells in the breast (ypT0/is) and 2) no residual invasive tumor cells in the breast and axillary lymph nodes (ypT0/is ypN0). Association between pCR and clinicopathologic characteristics and treatment were evaluated using chi-square test and multivariable logistic regression. Kaplan-Meier analysis and log-rank test, stratified by other prognostic factors, were conducted to compare overall survival between patients who achieved pCR and patients who did not. Overall, 4.4% of nonmetastatic patients received neoadjuvant chemotherapy. The median age of preoperatively treated patients was 50 years. pCR rates were 18.1% (pCR ypT0/is) and 14.4% (pCR ypT0/is ypN0), respectively. pCR rate was the highest among women who had higher grade, smaller size, estrogen receptor negative, human epidermal growth factor receptor 2-positive disease or receiving taxane-based neoadjuvant chemotherapy. Patients who achieved pCR had better overall survival than those who did not. In subgroup analysis, the survival advantage was only significant among women with estrogen receptor-negative tumors. Patients with poor prognostic profile are more likely to achieve pCR and particularly when receiving taxane-containing chemotherapy. pCR is a significant prognostic factor for overall survival especially in estrogen receptor-negative breast cancers.

Matched MeSH terms: Carcinoma, Ductal, Breast/pathology
Expression of DDR1 and DVL1 in invasive ductal and lobular breast carcinoma does not correlate with histological type, grade and hormone receptor status

Ameli F, Rose IM, Masir N

Asian Pac J Cancer Prev, 2015;16(6):2385-90.
PMID: 25824769

BACKGROUND: Invasive ductal (IDC) and lobular (ILC) carcinomas are the common histological types of breast carcinoma which are difficult to distinguish when poorly differentiated. Discoidin domain receptor (DDR1) and Drosophila dishevelled protein (DVL1) were recently suggested to differentiate IDC from ILC.
OBJECTIVES: To assess the expression of DDR1 and DVL1 and their association with histological type, grading and hormonal status of IDC and ILC.
MATERIALS AND METHODS: This cross sectional study was conducted on IDC and ILC breast tumours. Tumours were immunohistochemically stained for (DDR1) and (DVL1) as well as estrogen receptor (ER), progesterone receptor (PR) and C-erbB2 receptor. Demographic data including age and ethnicity were obtained from patient records.
RESULTS: A total of 51 cases (30 IDCs and 21 ILCs) were assessed. DDR1 and DVL1 expression was not significantly associated with histological type (p=0.57 and p=0.66 respectively). There was no association between DDR1 and DVL1 expression and tumour grade (p=0.32 and p=1.00 respectively), ER (p=0.62 and 0.50 respectively), PR (p=0.38 and p=0.63 respectively) and C-erbB2 expression (p=0.19 and p=0.33 respectively) in IDC. There was no association between DDR1 and DVL1 expression and tumour grade (p=0.52 and p=0.33 respectively), ER (p=0.06 and p=0.76 respectively), PR (p=0.61 and p=0.43 respectively) and C-erbB2 expression (p=0.58 and p=0.76 respectively) in ILC.
CONCLUSIONS: This study revealed that DDR1 and DVL1 are present in both IDC and ILC regardless of the tumour differentiation. More studies are needed to assess the potential of these two proteins in distinguishing IDC from ILC in breast tumours.

Matched MeSH terms: Carcinoma, Ductal, Breast/pathology
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/pathology*
In human invasive breast ductal carcinoma, tumor stromal macrophages and tumor nest macrophages have distinct relationships with clinicopathological parameters and tumor angiogenesis

Ch'ng ES, Tuan Sharif SE, Jaafar H

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

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

Matched MeSH terms: Carcinoma, Ductal, Breast/pathology*
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/pathology*
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/pathology*
Expression of Bax and Bcl-2 in tumour cells and blood vessels of breast cancer and their association with angiogenesis and hormonal receptors

Jaafar H, Abdullah S, Murtey MD, Idris FM

Asian Pac J Cancer Prev, 2012;13(8):3857-62.
PMID: 23098483

A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity.

Matched MeSH terms: 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/pathology
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/pathology*
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/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/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/pathology
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 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*
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/pathology
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/pathology

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