Multidrug resistance in locally advanced breast cancer

WOS: 000241725800004PubMed ID: 17033200Background: Advanced breast cancer cases can still be encountered resulting in poor prognosis. The primary treatment for these patients is chemotherapy, and multidrug resistance (MDR) is a serious obstacle in the treatment. Detecting drug resistance before first-line chemotherapy may increase the patient's survival. In this study, the role of MDR is evaluated in locally advanced breast cancer patients. Methods: Reverse transcriptase polymerase chain reaction was used for the detection of MDR genes, ABCB1 and ABCC1. Immunohistochemistry was used for the detection of MDR proteins, P-glycoprotein (Pgp) and MDR-associated protein 1. Results: Breast tissues from 25 patients both before and after chemotherapy were examined. Five patients were unresponsive to chemotherapy. Four had ABCB1 gene expression induced by chemotherapy, and Pgp positivity was detected in 9 patients after chemotherapy. Both the induction of ABCB1 gene expression (p < 0.001) and Pgp positivity (p < 0.001) during chemotherapy were significantly related with clinical response. Although 80% of the clinically unresponsive patients had ABCC1 gene expression, the relation between ABCC1 expression and clinical drug response was not significant. Conclusion: In locally advanced breast cancer, ABCB1 gene expression during chemotherapy contributes to clinical unresponsiveness. However, ABCC1 gene expression did not correlate strongly with the clinical response. Copyright (c) 2006 S. Karger AG, Base

Thyroid Fnac Containing Hürthle Cells And Hürthle-Like Cells: A Study Of 128 Cases

Aim: It is a diagnostic challenge to differentiate benign and malignant cytology in the presence of Hürthle cells. In our previous study, it was determined that in fine needle aspirations (FNA), the malignancy outcome of the Hürthle cells containing group tend to be papillary thyroid carcinoma (PTC) in a higher percentage. The most common misinterpretation is caused by PTC cells with large cytoplasm-like Hürthle cells. The aim of this study is to predict histologic outcome of the nodules, which have Hürthle cells in FNA according to cytological, clinical features, and BRAFV600E mutation status. Materials and Methods: Detailed cytological features of 128 cases were compared with histopathological diagnosis. The analysis of BRAFV600E mutation of the PTC cases were performed by real-time polymerase chain reaction. Results: The neoplastic outcome was increased statistically significantly with younger age (P = 0.020), increase in cellular dyshesion (P = 0.016), presence of nuclear budding (P = 0.046), and granular chromatin (P = 0.003). Nuclear budding (P = 0.014), granular chromatin (P = 0.012), and hypoechoic nodules in ultrasonography (P = 0.011) were significant independent factors for the increase in the malignancy risk. Increased lymphocytes (P= 0.015) and colloid were related to non-neoplastic outcome. According to the surgical outcome, more than half of the malign cases were PTC (74%). BRAFV600E mutation was detected in 27.8% of the PTC cases. Conclusion: PTC cases containing Hürthle cell-like cells may lead to diagnostic errors. Nuclear budding and granular chromatin of Hürthle cells are significant, remarkable findings to predict the outcome of neoplasm and malignancy.PubMedWoSScopu

Microrna Expression Profiling Identifies A Four Microrna Signature As A Novel Diagnostic And Prognostic Biomarker In Triple Negative Breast Cancers

Triple Negative Breast Cancers (TNBC) is a heterogeneous disease at the molecular and clinical level with poor outcome. Molecular subclassification of TNBCs is essential for optimal use of current therapies and for development of new drugs. microRNAs (miRNA) are widely recognized as key players in cancer progression and drug resistance; investigation of their involvement in a TNBC cohort may reveal biomarkers for diagnosis and prognosis of TNBC. Here we stratified a large TNBC cohort into Core Basal (CB, EGFR and/or CK5, 6 positive) and five negative (5NP) if all markers are negative. We determined the complete miRNA expression profile and found a subset of miRNAs specifically deregulated in the two subclasses., We identified a 4-miRNA signature given by miR-155, miR-493, miR-30e and miR-27a expression levels, that allowed subdivision of TNBCs not only into CB and 5NP subgroups (sensitivity 0.75 and specificity 0.56; AUC=0.74) but also into high risk and low risk groups. We tested the diagnostic and prognostic performances of both the 5 IHC marker panel and the 4-miRNA expression signatures, which clearly identify worse outcome patients in the treated and untreated subcohorts. Both signatures have diagnostic and prognostic value, predicting outcomes of patient treatment with the two most commonly used chemotherapy regimens in TNBC: anthracycline or anthracycline plus taxanes. Further investigation of the patients' overall survival treated with these regimens show that regardless of IHC group subdivision, taxanes addition did not benefit patients, possibly due to miRNA driven taxanes resistance. TNBC subclassification based on the 5 IHC markers and on the miR-155, miR-493, miR-30e, miR-27a expression levels are powerful diagnostic tools. Treatment choice and new drug development should consider this new subtyping and miRNA expression signature in planning low toxicity, maximum efficacy therapies.PubMedWo

Androgen receptor expression status defines novel potential therapeutic targets.

<p>mRNA expression profiling of 160 TNBC cases was dichotomized according to their AR immunohistochemical status (AR negative <i>vs</i> AR positive). As expected, AR mRNA was significantly up-regulated in AR-positive cases (logFC 2.33; p<0.01; <b>A</b>). Among the deregulated mRNAs, CDK6 showed significantly higher expression in AR-negative cases (logFC -1.16; p<0.01; <b>B</b>).</p

Differentially expressed genes in TNBCs according to AR status.

<p>Differentially expressed genes in TNBCs according to AR status.</p

Androgen receptor mRNA expression is down-regulated in TNBC cases.

<p>Expression microarray results of the TCGA consortium data set was analyzed, and statistical significance was calculated using the Oncomine website (<a href="http://www.oncomine.org" target="_blank">www.oncomine.org</a>). Box plots show differences in mRNA expression between the different classes according to TNBC (<b>A</b>), HER2 (<b>B</b>), ER (<b>C</b>), and PR (<b>D</b>) status. Data are presented as box plot distribution (Line within the boxes =  median value).</p

Androgen receptor expression is low in TNBC cases.

<p>AR expression distribution in the considered cancers. (<b>A</b>) Nuclear AR staining was significantly lower in TNBC specimens than in HER2-positive and ER/PR-positive tissues (p < 0.001). The trend toward expression differences among different ethnicities was not significant. Among TNBCs, 5NP cancers showed a higher frequency of AR expression (<i>p</i> = ns). Numbers represent TMA cores available for the analysis. Black  =  AR positive cases, gray  =  AR negative cases. (<b>B</b>) Representative images of AR immunostaining in the three cancer subtypes (HER2-positive, ER/PR-positive, and TNBC). (Original magnification, 200×)</p

Immunohistochemical profiles of the considered series.

<p>Immunohistochemical profiles of the considered series.</p