Evi Lianidou

Bio: Evi Lianidou is an academic researcher from National and Kapodistrian University of Athens. The author has contributed to research in topics: Circulating tumor cell & Liquid biopsy. The author has an hindex of 50, co-authored 181 publications receiving 7035 citations. Previous affiliations of Evi Lianidou include Toronto Western Hospital.

Prognostic Value of Mature MicroRNA-21 and MicroRNA-205 Overexpression in Non–Small Cell Lung Cancer by Quantitative Real-Time RT-PCR

Abstract: Background: microRNA (miRNA) expression profiles are being intensively investigated for their involvement in carcinogenesis. We evaluated the prognostic value of mature microRNA-21 (miR-21) and mature microRNA-205 (miR-205) overexpression in non–small cell lung cancer (NSCLC). Patients and methods: We studied 48 pairs of NSCLC fresh frozen tissue specimens collected at time of surgery and before chemotherapy. Highly specific amplification and quantification of mature miR-21 and mature miR-205 was achieved using looped real time RT-PCR. Results: miRNA expression, determined by real time RT-PCR, was defined by ΔΔCt measurements. We detected overexpression of mature miR-21 in 25 (52.0%) of the 48 NSCLC paired specimens and overexpression of miR-205 in 31 (64.6%). Overexpression was assessed after comparison of miRNA expression in NSCLC tissues and in their corresponding noncancerous tissues with respect to U6 expression. During the follow-up period, 29 of 48 (60.4%) patients relapsed, and 23 of 48 died (47.9%). Mature miR-21 was upregulated in 16 of 29 (55.2%) patients who relapsed and 15 of 23 (65.2%) patients who died. Mature miR-205 was overexpressed in 19 of 29 patients who relapsed (65.5%) and 15 of 23 patients who died (65.2%). Mature miR-21 overexpression correlated with overall survival (OS) of the patients ( P = 0.027), whereas overexpression of mature miR-205 did not. Conclusions: Our results suggest that overexpression of mature miR-21 is an independent negative prognostic factor for OS in NSCLC patients.

Predictive and Prognostic Value of Peripheral Blood Cytokeratin-19 mRNA-Positive Cells Detected by Real-Time Polymerase Chain Reaction in Node-Negative Breast Cancer Patients

Abstract: Purpose To evaluate the predictive and prognostic value of peripheral blood cytokeratin-19 (CK-19) mRNA-positive cells in axillary lymph node–negative breast cancer patients. Patients and Methods Peripheral blood was obtained from 167 node-negative breast cancer patients before the initiation of any systemic adjuvant therapy, and was analyzed for the presence of CK-19 mRNA-positive cells using a real time polymerase chain reaction assay. The association with known prognostic factors and the effect of CK-19 mRNA-positive cells on patients’ prognosis was investigated. Results

Cytokeratin-19 mRNA-Positive Circulating Tumor Cells After Adjuvant Chemotherapy in Patients With Early Breast Cancer

Abstract: Purpose To evaluate the prognostic significance of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in peripheral blood of women with early-stage breast cancer after the completion of adjuvant chemotherapy. Patients and Methods Blood was obtained from 437 patients with early breast cancer before the start and after the completion of adjuvant chemotherapy, and the presence of CK-19 mRNA-positive CTCs was assessed by real-time reverse transcriptase polymerase chain reaction. Interaction with known prognostic factors and association of CTCs with clinical outcome were investigated. Results CK-19 mRNA-positive CTCs were detected before chemotherapy in 179 patients (41.0%). After adjuvant chemotherapy, a significant change in CK-19 status was observed, as status for 51% of patients with initially CK-19 mRNA-positive disease turned negative, and status for 22% of patients with initially CK-19 mRNA-negative disease became positive (McNemar test P .004). The detection of CK-19 mRNA-positive CTCs postchemotherapy was associated with involvement of more than three axillary lymph nodes (P .026). Clinical relapses and disease-related deaths were significantly increased in patients with detectable postchemotherapy CK-19 mRNA-positive CTCs (both P .001, respectively). Disease-free and overall survival were significantly reduced in patients with detectable CK-19 mRNA-positive CTCs postchemotherapy (P .001 and P .001, respectively). In multivariate analysis, the detection of CK-19 mRNA-positive CTCs before and after adjuvant chemotherapy was an independent factor associated with reduced disease-free survival (P .001) and overall survival (P .003). Conclusion The detection of CK-19 mRNA-positive CTCs in the blood after adjuvant chemotherapy is an independent risk factor indicating the presence of chemotherapy-resistant residual disease.

Prognostic Value of the Molecular Detection of Circulating Tumor Cells Using a Multimarker Reverse Transcription-PCR Assay for Cytokeratin 19, Mammaglobin A, and HER2 in Early Breast Cancer

Abstract: Purpose: To investigate the prognostic value of the molecular detection of circulating tumor cells ( CTCs ) using three markers [cytokeratin 19 ( CK19 ), mammaglobin A ( MGB1 ), and HER2 ] in early breast cancer. Experimental Design: CK19mRNA+, MGB1mRNA+, and HER2mRNA+ cells were detected using real-time ( CK19 ) and nested ( MGB1 and HER2 ) reverse transcription-PCR in the peripheral blood of 175 women with stage I to III breast cancer before the initiation of adjuvant chemotherapy. The detection of CTCs was correlated with clinical outcome. In 10 patients, immunofluorescence staining experiments were done to investigate the coexpression of cytokeratin, MGB1, and HER2 in CTCs. Results: CK19mRNA+, MGB1 mRNA+, and HER2 mRNA+ cells were detected in 41.1%, 8%, and 28.6% of the 175 patients, respectively. Patients had one of the following molecular profiles: CK19mRNA+/ MGB1 mRNA+/ HER2 mRNA+ ( n = 8), CK19mRNA+/ MGB1 mRNA+/ HER2 mRNA− ( n = 1), CK19mRNA+/ MGB1 mRNA−/ HER2 mRNA+ ( n = 42), CK19mRNA+/ MGB1 mRNA−/ HER2 mRNA− ( n = 21), CK19mRNA−/ MGB1 mRNA+/ HER2 mRNA− ( n = 5), and CK19mRNA−/ MGB1 mRNA−/ HER2 mRNA− ( n = 98). Double-immunofluorescence experiments confirmed the following CTC phenotypes: CK+/ MGB1 +, CK+/ MGB1 −, CK−/ MGB1 +, CK+/ HER2 +, CK+/ HER2 −, MGB1 +/ HER2 −, and MGB1 +/ HER2 +. In univariate analysis, the detection of CK19mRNA+, MGB1 mRNA+, and HER2mRNA+ cells was associated with shorter disease-free survival (DFS; P P = 0.001, and P MGB1 mRNA+ cells was associated with worse overall survival ( P = 0.044 and 0.034, respectively). In multivariate analysis, estrogen receptor–negative tumors and the detection of CK19 mRNA+ and MGB1 mRNA+ cells were independently associated with worse DFS. Conclusion: The detection of peripheral blood CK19 mRNA+ and MGB1 mRNA+ cells before adjuvant chemotherapy predicts poor DFS in women with early breast cancer.

Different Prognostic Value of Cytokeratin-19 mRNA–Positive Circulating Tumor Cells According to Estrogen Receptor and HER2 Status in Early-Stage Breast Cancer

Abstract: Purpose To examine the prognostic value of cytokeratin-19 (CK-19) mRNA–positive circulating tumor cells (CTCs) in early-stage breast cancer patients focusing on clinically relevant subgroups based on estrogen receptor (ER) and HER2 expression. Patients and Methods CK-19 mRNA–positive CTCs were detected by real-time reverse transcriptase polymerase chain reaction in the blood of 444 consecutive, stage I-III, breast cancer patients before initiation of adjuvant chemotherapy. The association between detection of CK-19 mRNA–positive CTCs and clinical outcome was analyzed for patients with ER-positive, ER-negative, triple-negative, HER2positive, and ER-positive/HER2-negative tumors. Results CK-19 mRNA–positive CTCs were detected in 181 (40.8%) of 444 patients; 109 (41.9%) of 260 patients with ER-positive tumors; 71 (40.6%) of 175 patients with ER-negative tumors; 27 (35%) of 77 patients with triple-negative tumors; 35 (39.8%) of 88 patients with HER2-positive tumors; and 82 (44.1%) of 186 patients with ER-positive/HER2-negative tumors. After a median follow-up of 53.5 months, patients with CK-19 mRNA–positive CTCs experienced reduced disease-free survival (DFS; P .001) and overall survival (OS; P .001); this was mainly observed in patients with ER-negative (P .001 and P .001, respectively) but not ER-positive tumors (P .172 and P .425, respectively) and in patients with triple-negative (P .008 and P .001, respectively) and HER2-positive (P .023 and P .040, respectively) but not ER-positive/HER2-negative tumors (P .210 and P .578, respectively). In multivariate analysis, the interaction between CK-19 mRNA–positive CTCs and ER status was the strongest independent prognostic factor for reduced DFS (hazard ratio [HR], 3.808; 95% CI, 2.415 to 6.003; P .001) and OS (HR, 4.172; 95% CI, 2.477 to 9.161; P .001). Conclusion Detection of CK-19 mRNA–positive CTCs before adjuvant chemotherapy predicts poor clinical outcome mainly in patients with ER-negative, triple-negative, and HER2-positive early-stage breast cancer. J Clin Oncol 25:5194-5202. © 2007 by American Society of Clinical Oncology

Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update.

Abstract: Purpose To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer.

Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update

Abstract: Purpose.—To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in b...