The epithelial to mesenchymal transition (EMT) is a developmental process enabling epithelial cells to gain a migratory mesenchymal phenotype. In cancer, this process contributes to metastases; however the regulatory signals and mechanistic details are not fully elucidated. Here, we sought to identify the subset of genes regulated in lung cancer by ZEB1, an E-box transcriptional repressor known to induce EMT.
View Article and Find Full Text PDFBackground: To address the clinical relevance of molecular detection of occult breast cancer in sentinel lymph nodes and nonsentinel axillary lymph nodes (ALN), we initiated the Minimally Invasive Molecular Staging of Breast Cancer (MIMS) trial, a multi-institutional prospective cohort study. This trial represents the first prospective cohort study in which a multimarker, real-time reverse transcription polymerase chain reaction (RT-PCR) analysis was applied to the detection of breast cancer micrometastases in ALN.
Materials And Methods: Sentinel and/or nonsentinel ALN from 501 breast cancer subjects with T1-T3 primary tumors were analyzed by standard histopathology and multimarker, real-time RT-PCR analysis.
We have previously reported that a quantitative reverse transcription (QRT)-PCR assay accurately analyzes sentinel lymph nodes (SLNs) from breast cancer patients. The aim of this study was to assess a completely automated, cartridge-based version of the assay for accuracy, predictive value, and reproducibility. The triplex (two markers + control) QRT-PCR assay was incorporated into a single-use cartridge for point-of-care use on the GeneXpert system.
View Article and Find Full Text PDFColorectal cancer (CRC) is the second most frequent cause of cancer-related death in the United States. To determine whether certain molecular markers might be prognostic for survival, we measured by quantitative real-time RT-PCR the expression levels of 15 previously studied genes that are known to be up-regulated or down-regulated in the progression of epithelial cancers. The tumor samples were extracted from formalin-fixed paraffin-embedded primary tissues derived from patients with Stage II CRC who developed disease recurrence within two years (n=10), or were disease-free for at least 4 years (n=12).
View Article and Find Full Text PDFJ Thorac Cardiovasc Surg
March 2008
Objective: We hypothesized that clinical outcome of resected early-stage adenocarcinoma of the lung can be predicted by the expression of a few critically important genes as measured by quantitative real-time reverse-transcriptase polymerase chain reaction in formalin-fixed paraffin-embedded primary tumors.
Methods: Twenty-two prognostic genes for the metastatic phenotype were identified through complementary DNA microarray analysis of 4 cancer cell lines and bioinformatics analysis. Expression levels of a subset of these genes (n = 13) were measured by real-time time reverse-transcriptase polymerase chain reaction in formalin-fixed paraffin-embedded primary adenocarcinoma from patients whose disease recurred within 2 years (n = 9) and in patients who did not have a recurrence (n = 11).
Background: We sought to examine the detection rate of cancer cells in peripheral blood (PBL) and in bone marrow (BM) using an established 7-gene marker panel and evaluated whether there were any definable associations of any individual gene with traditional predictors of prognosis.
Methods: Patients with T1-T3 primary breast cancer were enrolled into a prospective, multi-institutional cohort study. In this interim analysis 215 PBL and 177 BM samples were analyzed by multimarker, real-time RT-PCR analysis designed to detect circulating and disseminated breast cancer cells.
A discrepancy exists between mortality and incidence rates between African-American and European-American women in South Carolina. The relationship between tumor grade and the estrogen/ progesterone receptor status is different in African-American and European-American women. African-American women with breast cancer should be encouraged to participate in clinical trials, with the goal of identifying biological factors that might facilitate the detection of tumors at an earlier stage and the development of more effective therapies.
View Article and Find Full Text PDFBecause of its high fatality rate and our inability to detect esophageal disease early in its development, esophageal cancer represents a significant medical and public health challenge. The mortality statistics underline the importance of focusing on prevention of these conditions as a matter of state and national public health priority. Unfortunately, the measures needed for primary prevention of these conditions do not seem as clear-cut for populations at highest risk of this disease (i.
View Article and Find Full Text PDFTo augment cytological diagnosis of pancreatic ductal adenocarcinoma (PDAC) in tissue samples obtained by minimally invasive endoscopic ultrasound-guided fine needle aspiration, we investigated whether a small set of molecular markers could accurately distinguish PDAC from chronic pancreatitis (CP). Expression levels of 29 genes were first determined by quantitative real-time RT-PCR in a training set of tissues in which the final diagnosis was PDAC (n=20) or CP (n=10). Using receiver operator characteristic curve analysis, we determined that the single gene with the highest diagnostic accuracy for discrimination of CP vs.
View Article and Find Full Text PDFBackground: Pathologic evaluation may lack the sensitivity required for accurate staging of the axilla in breast cancer patients. We have completed enrollment of a multi-institutional prospective cohort study designed to determine if molecular analyses can improve axillary staging. In subset analyses, we have attempted to address the following questions: (1) Does molecular analysis improve the sensitivity of sentinel lymph node biopsy (SLNB) and (2) is the sentinel lymph node (SLN) hypothesis valid at the molecular level?
Methods: Four hundred eighty-nine subjects with T1, T2, or T3 breast cancer and no evidence of axillary lymph node (ALN) involvement were enrolled.
There is increasing evidence that molecular detection of micrometastatic breast cancer in the axillary lymph nodes (ALN) of breast cancer patients can improve staging. Molecular analyses of samples obtained from the Minimally Invasive Molecular Staging of Breast Cancer Trial (n = 489 patients) indicate that whereas the majority of molecular markers are informative for the detection of metastatic breast cancer (significant disease burden), only a few are sensitive for the detection of micrometastatic disease (limited disease burden). Frequency distribution and linear regression analyses reveal that relative levels of gene expression are highly correlated with apparent sensitivity for the detection of micrometastic breast cancer (P < 0.
View Article and Find Full Text PDFEsophageal adenocarcinoma (EA) is increasing faster than any other cancer in the U.S. In this report, we first show that EA can be distinguished from normal esophagus (NE) and esophageal squamous cell carcinoma by plotting expression values for EpCam, TFF1, and SBEM in three-dimensional Euclidean space.
View Article and Find Full Text PDFObjectives: The recurrence of disease after the complete resection of early stage non-small cell lung cancer (NSCLC) indicates that undetected metastases were present at the time of surgery. Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) is a highly sensitive technique for detecting rare gene transcripts that may indicate the presence of cancer cells, and endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is a minimally invasive technique for the nonoperative sampling of mediastinal lymph nodes. The aim of this study was to determine whether these two techniques could enhance the preoperative detection of occult metastases.
View Article and Find Full Text PDFEpCAM (epithelial cell adhesion molecule) is a cell surface molecule that is known to be highly expressed in colon and other epithelial carcinomas. EpCAM is involved in cell-to-cell adhesion and has been the target of antibody therapy in several clinical trials. To assess the value of EpCAM as a novel target for breast cancer gene therapy, we performed real-time reverse transcription-PCR to quantify the level of EpCAM mRNA expression in normal breast tissue and primary and metastatic breast cancers.
View Article and Find Full Text PDFObjective: We sought to establish the clinical relevance of micrometastatic disease detected by reverse transcription polymerase chain reaction (RT-PCR) in axillary lymph nodes (ALN) of breast cancer patients.
Background: The presence of ALN metastases remains one of the most valuable prognostic indicators in women with breast cancer. However, the clinical relevance of molecular detection of micrometastatic breast cancer in sentinel lymph nodes (SLN) and nonsentinel ALN has not been established.
Purpose: The goal of this study was to develop a molecular diagnostic assay to detect circulating breast cancer cells in the peripheral blood for the purpose of staging breast cancer. Our aim was to make available an assay that was not limited by the low concentration of circulating breast cancer cells and the background gene expression that is typically found in peripheral blood.
Experimental Design: In this study, we investigated the ability of two new technologies to significantly enhance the quantification of gene expression in the peripheral blood: enrichment by a novel porous barrier density gradient centrifugation technology; and multimarker real-time reverse transcription-PCR (RT-PCR).
The clinical management of non-small cell lung cancer (NSCLC) would benefit greatly by a test that was able to detect small amounts of NSCLC in the peripheral blood. In this report, we used a novel strategy to enrich tumor cells from the peripheral blood of 24 stage I to IV NSCLC patients and determined expression levels for six cancer-associated genes (lunx, muc1, KS1/4, CEA, CK19, and PSE). Using thresholds established at three standard deviations above the mean observed in 15 normal controls, we observed that lunx (10 of 24, 42%), muc1 (5 of 24, 21%), and CK19 (5 of 24, 21%) were overexpressed in 14 of 24 (58%) peripheral blood samples obtained from NSCLC patients.
View Article and Find Full Text PDFBackground: The rapid evolution of molecular technology and novel markers provides the opportunity to establish a more effective means to detect micrometastatic breast cancer. Given the controversies concerning application and clinical relevance, this review critically evaluates the current status of these molecular staging technologies.
Data Sources: Breast cancer literature addressing (1).
Mediastinal lymph nodes are the most common site of tumor spread in non-small cell lung cancer (NSCLC). We hypothesized that micrometastatic disease could be detected by reverse transcription-polymerase chain reaction (RT-PCR) for expression of human telomerase reverse transcriptase (hTERT) in mediastinal lymph nodes and that a minimally invasive technique (endoscopic ultrasound-guided fine-needle aspiration [EUS-FNA]) is capable of sampling lymph nodes for PCR analysis without surgery. Mediastinal lymph nodes were sampled with EUS-FNA in patients with NSCLC and negative control subjects undergoing EUS for benign disease.
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