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  1. Wan Abdul Rahman WF, Fauzi MH, Jaafar H
    Asian Pac J Cancer Prev, 2014;15(19):8441-5.
    PMID: 25339043
    BACKGROUND: Paired-like homeodomain transcription factor 2 (PITX2) is another new marker in breast carcinoma since hypermethylation at P2 promoter of this gene was noted to be associated with poor prognosis. We investigated the expression of PITX2 protein using immunohistochemistry in invasive ductal carcinoma and its association with the established growth receptors such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2).

    METHODS: We conducted a cross sectional study using 100 samples of archived formalin-fixed paraffin embedded tissue blocks of invasive ductal carcinoma and stained them with immunohistochemistry for PITX2, ER, PR and HER2. All HER2 with scoring of 2+ were confirmed with chromogenic in-situ hybridization (CISH).

    RESULTS: PITX2 protein was expressed in 53% of invasive ductal carcinoma and lack of PITX2 expression in 47%. Univariate analysis revealed a significant association between PITX2 expression with PR (p=0.001), ER (p=0.006), gland formation (p=0.044) and marginal association with molecular subtypes of breast carcinoma (p=0.051). Combined ER and PR expression with PITX2 was also significantly associated (p=0.003) especially in double positive cases. Multivariate analysis showed the most significant association between PITX2 and PR (RR 4.105, 95% CI 1.765-9.547, p=0.001).

    CONCLUSION: PITX2 is another potential prognostic marker in breast carcinoma adding significant information to established prognostic factors of ER and PR. The expression of PITX2 together with PR may carry a very good prognosis.

    Matched MeSH terms: Carcinoma, Ductal, Breast/secondary
  2. Ng CH, Pathy NB, Taib NA, Ho GF, Mun KS, Rhodes A, et al.
    Asian Pac J Cancer Prev, 2014;15(18):7959-64.
    PMID: 25292095
    The significance of the single hormone receptor positive phenotype of breast cancer is still poorly understood. The use of hormone therapy has been found to be less effective for this type, which has a survival outcome midway between double positive and double negative phenotypes. The aim of this study was to investigate differences in patient and tumor characteristics and survival between double-receptor positive (ER+PR+), double receptor negative (ER-PR-) and single receptor positive (ER+PR- and ER-PR+) breast cancer in an Asian setting. A total of 1,992 patients with newly diagnosed stage I to IV breast cancer between 2003 and 2008, and where information on ER and PR were available, were included in this study. The majority of patients had ER+PR+ tumors (n=903: 45.3%), followed by 741 (37.2%) ER-PR-, 247 (12.4%) ER+PR-, and 101 (5.1%) ER-PR+ tumors. Using multivariate analysis, ER+PR- tumors were 2.4 times more likely to be grade 3 compared to ER+PR+ tumors. ER+PR- and ER-PR+ tumors were 82% and 86% respectively less likely to be grade 3 compared with ER-PR- tumors. ER-PR+ tumours were associated with younger age. There were no survival differences between patients with ER+PR+ and ER-PR+ tumors. However, ER+PR- tumors have poorer survival compared with ER+PR+ tumours. ER-PR- tumours had the worst survival. Adjuvant hormonal therapy with tamoxifen was found to have identical survival advantage in patients with ER+PR+ and ER-PR+ tumors whereas impact was slightly lower in patients with ER+PR- tumors. In conclusion, we found ER+PR- tumors to be more aggressive and have poorer survival when compared to ER+PR+ tumors, while patients with ER-PR+ tumours were younger, but had a similar survival to their counterparts with ER+PR+ tumours.
    Matched MeSH terms: Carcinoma, Ductal, Breast/secondary
  3. 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/secondary
  4. Looi LM, Cheah PL, Zhao W, Ng MH, Yip CH
    Malays J Pathol, 2006 Dec;28(2):83-6.
    PMID: 18376796 MyJurnal
    Metastasising ability connotes one of the most important life-threatening properties of malignant neoplasms. Recent studies indicate that CD44 proteins, multifunctional cell adhesion molecules which contribute to "homing" of lymphocytes to lymph nodes as well as cell-cell and cell-matrix interactions, are potential markers of tumour progression. However, whether CD44 expression by human tumours contribute to increased metastatic risk remains controversial. In an attempt to clarify its role in breast cancer, we have investigated the correlation between CD44 expression by breast carcinoma and the presence of axillary lymph node metastases. CD44 expression was detected using a standard immunoperoxidase method on formalin-fixed, paraffin-embedded, primary infiltrating ductal breast carcinoma tissues taken from 60 female patients who underwent mastectomy with axillary node clearance. Tumours were graded according to the modified Bloom and Richardson criteria. 62% of patients had histologically-proven lymph node metastasis. 40% of primary cancers exhibited cytoplasmic membrane immunopositivity for CD44. 46% of primary tumours which have metastasied to axillary lymph nodes were CD44 positive whereas 30% of tumours which have not metastasised expressed CD44. CD44 positivity was expressed by 20% of grade 1, 31% grade 2 and 58% grade 3 tumours. Our results suggest that CD44 may have a role in the progression of breast cancer and emphasise the need to investigate its interaction with other mechanisms of cancer advancement.
    Matched MeSH terms: Carcinoma, Ductal, Breast/secondary
  5. Kaur G, Ismail R, Harun H
    Malays J Pathol, 2005 Dec;27(2):117-8.
    PMID: 17191395
    Metastatic eyelid tumours are rare and account for less than 2% of all eyelid neoplasms. We report a case of metastatic breast carcinoma to the eyelid in a 60-year-old Chinese lady presenting with a 2-year history of enlarging, painless nodular lower eyelid swelling. The 1 cm diameter lesion was provisionally diagnosed as a sebaceous cyst. However the excision biopsy revealed a mucinous carcinoma expressing oestrogen receptor protein. She had a past history of mastectomy one year previously and histology showed an infiltrating ductal carcinoma (oestrogen receptor status negative) without evidence of axillary lymph node metastasis. She had completed adjuvant radio- and chemotherapy. Further treatment of the current lesion involved a wide excision which did not show any residual malignancy. She had no other evidence of metastasis and was treated with letrozol. We highlight this case to create awareness among clinicians and opthalmologists on the possibility of metastatic disease as a cause of eyelid swelling, especially in patients with a history of cancer. It may also be the first sign of metastatic disease of an internal malignancy. A review of the literature is also presented.
    Matched MeSH terms: Carcinoma, Ductal, Breast/secondary*
  6. Khoo JJ, Ng CS, Sabaratnam S, Arulanantham S
    Asian Pac J Cancer Prev, 2016;17(3):1149-55.
    PMID: 27039740
    BACKGROUND: Examination of sentinel lymph node (SLN) biopsies provides accurate nodal staging for breast cancer and plays a key role in patient management. Procurement of SLNs and the methods used to process specimens are equally important. Increasing the level of detail in histopathological examination of SLNs increases detection of metastatic tumours but will also increase the burden of busy laboratories and thus may not be carried out routinely. Recommendation of a reasonable standard in SLN examination is required to ensure high sensitivity of results while maintaining a manageable practice workload.

    MATERIALS AND METHODS: Twenty-four patients with clinically node-negative breast cancer were recruited. Combined radiotracer and blue dye methods were used for identification of SLNs. The nodes were thinly sliced and embedded. Serial sectioning and immunohistochemical (IHC) staining against AE1/AE3 were performed if initial HandE sections of the blocks were negative.

    RESULTS: SLNs were successfully identified in all patients. Ten cases had nodal metastases with 7 detected in SLNs and 3 detected only in axillary nodes (false negative rate, FNR=30%). Some 5 out of 7 metastatic lesions in the SLNs (71.4%) were detected in initial sections of the thinly sliced tissue. Serial sectioning detected the remaining two cases with either micrometastases or isolated tumour cells (ITC).

    CONCLUSIONS: Thin slicing of tissue to 3-5mm thickness and serial sectioning improved the detection of micro and macro-metastases but the additional burden of serial sectioning gave low yield of micrometastases or ITC and may not be cost effective. IHC validation did not further increase sensitivity of detection. Therefore its use should only be limited to confirmation of suspicious lesions. False negative cases where SLNs were not involved could be due to skipped metastases to non-sentinel nodes or poor technique during procurement, resulting in missed detection of actual SLNs.

    Matched MeSH terms: Carcinoma, Ductal, Breast/secondary*
  7. 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/secondary*
  8. Reddy SC, Madhavan M, Mutum SS
    Ophthalmologica, 2000 Sep-Oct;214(5):368-72.
    PMID: 10965254 DOI: 10.1159/000027523
    Breast carcinoma is the most common primary tumor producing intraocular metastasis. Metastases to the iris and ciliary body are relatively rare. The authors report a case of a 61-year-old lady, operated for carcinoma of the left breast 3 years back, who presented with symptoms and signs of acute narrow-angle glaucoma in the right eye. A diffuse whitish plaque-like mass in the upper nasal quadrant of the iris with an episcleral nodule on the limbus in the corresponding area and all the signs of acute narrow-angle glaucoma were present in the right eye. Intraocular pressure was controlled medically. Fine-needle aspiration cytology from the episcleral nodule showed malignant cells. Histopathology of the excised nodule showed metastatic poorly differentiated carcinoma, and the cellular pattern was similar to the carcinoma of the breast. There was no other metastasis anywhere in the body. Fine-needle aspiration cytology from an external lesion of the eye is a less invasive and easier procedure than paracentesis to diagnose the metastatic nature of the lesions. The rare features in our case are the clinical presentation as acute glaucoma and the ocular structures being the first and only site of metastasis.
    Matched MeSH terms: Carcinoma, Ductal, Breast/secondary*
  9. Looi LM, Azura WW, Cheah PL, Ng MH
    Pathology, 2001 Aug;33(3):283-6.
    PMID: 11523925
    This investigation was carried out to gain insight into the prevalence of pS2 expression in invasive ductal breast carcinoma in the Malaysian population and its correlation with oestrogen receptor (ER) protein expression and tumour aggressiveness. Seventy consecutive infiltrating ductal breast carcinomas treated with mastectomy and axillary lymph node clearance were investigated, using the standard avidin-biotin complex immunoperoxidase method with microwave antigen retrieval and commercial monoclonal antibodies (Dako), for expression of pS2 and human ER. This was correlated against histological grade (modified Bloom and Richardson) and the presence of axillary lymph node metastasis of these carcinomas. Four (5.7%) were grade 1, 40 (57.1%) grade 2 and 26 (37.1%) grade 3 tumours. A total of 45 (64%) showed histological evidence of axillary lymph node metastasis. Forty (57%) were ER-positive, while 31 (44%) were pS2-positive. There was a statistically significant correlation between pS2 and ER expressions (chi2-test with Yates correction: P<0.005). There was no correlation between pS2 expression and histological grade (P>0.1) and the presence of lymph node metastasis (P>0.1). Our findings support the views that pS2 may be a co-marker of endocrine responsiveness in invasive breast cancer and that it does not influence breast cancer biology in terms of potential for metastatic spread.
    Matched MeSH terms: Carcinoma, Ductal, Breast/secondary
  10. 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: Carcinoma, Ductal, Breast/secondary*
  11. Phua CE, Tang WH, Yusof MM, Saad M, Alip A, See MH, et al.
    Asian Pac J Cancer Prev, 2014;15(23):10263-6.
    PMID: 25556458
    BACKGROUND: The risk of febrile neutropaenia (FN) and treatment related death (TRD) with first line palliative chemotherapy for de novo metastatic breast cancer (MBC) remains unknown outside of a clinical trial setting despite its widespread usage. This study aimed to determine rates in a large cohort of patients treated in the University of Malaya Medical Centre (UMMC).

    MATERIALS AND METHODS: Patients who were treated with first line palliative chemotherapy for de novo MBC from 2002-2011 in UMMC were identified from the UMMC Breast Cancer Registry. Information collected included patient demographics, histopathological features, treatment received, including the different chemotherapy regimens, and presence of FN and TRD. FN was defined as an oral temperature >38.5° or two consecutive readings of >38.0° for 2 hours and an absolute neutrophil count <0.5x109/L, or expected to fall below 0.5x109/L (de Naurois et al, 2010). TRD was defined as death occurring during or within 30 days of the last chemotherapy treatment, as a consequence of the chemotherapy treatment. Statistical analysis was performed using the SPSS version 18.0 software. Survival probabilities were estimated using the Kaplan-Meier method and differences in survival compared using log-rank test.

    RESULTS: Between 1st January 2002 and 31st December 2011, 424 patients with MBC were treated in UMMC. A total of 186 out of 221 patients with de novo MBC who received first line palliative chemotherapy were analyzed. The mean age of patients in this study was 49.5 years (range 24 to 74 years). Biologically, ER status was negative in 54.4% of patients and Her-2 status was positive in 31.1%. A 5-flourouracil, epirubicin and cyclophosphamide (FEC) chemotherapy regimen was chosen for 86.6% of the cases. Most patients had multiple metastatic sites (58.6%). The main result of this study showed a FN rate of 5.9% and TRD rate of 3.2%. The median survival (MS) for the entire cohort was 19 months. For those with multiple metastatic sites, liver only, lung only, bone only and brain only metastatic sites, the MS was 18, 24, 19, 24 and 8 months respectively (p-value= 0.319).

    CONCLUSIONS: In conclusion, we surmise that FEC is a safe regimen with acceptable FN and TRD rates for de novo MBC.

    Matched MeSH terms: Carcinoma, Ductal, Breast/secondary
  12. Ch'ng ES, Tuan Sharif SE, Jaafar H
    Asian Pac J Cancer Prev, 2012;13(9):4445-52.
    PMID: 23167359
    BACKGROUND: Prognosis of breast cancer depends on classic pathological factors and also tumor angiogenesis. This study aimed to evaluate the clinicopathological factors of breast cancer in a tertiary centre with a focus on the relationship between tumor angiogenesis and clinicopathological factors.

    METHODS: Clinicopathological data were retrieved from the archived formal pathology reports for surgical specimens diagnosed as invasive ductal carcinoma, NOS. Microvessels were immunohistochemically stained with anti-CD34 antibody and quantified as microvessel density.

    RESULTS: At least 50% of 94 cases of invasive breast ductal carcinoma in the study were advanced stage. The majority had poor prognosis factors such as tumor size larger than 50mm (48.9%), positive lymph node metastasis (60.6%), and tumor grade III (52.1%). Higher percentages of estrogen and progesterone receptor negative cases were recorded (46.8% and 46.8% respectively). Her-2 overexpression cases and triple negative breast cancers constituted 24.5% and 22.3% respectively. Significantly higher microvessel density was observed in the younger patient age group (p=0.012). There were no significant associations between microvessel density and other clinicopathological factors (p>0.05).

    CONCLUSIONS: Majority of the breast cancer patients of this institution had advanced stage disease with poorer prognostic factors as compared to other local and western studies. Breast cancer in younger patients might be more proangiogenic.

    Matched MeSH terms: Carcinoma, Ductal, Breast/secondary*
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