Urinary Nuclear Matrix Protein as a Marker for Transitional Cell Carcinoma of the Urinary Tract

Carpinito, Gennaro A.; Stadler, Walter M.; Briggman, Joseph V.; Chodak, Gerald W.; Church, Paul; Lamm, Donald L.; Lange, Paul H.; Messing, Edward M.; Pasciak, Robert M.; Reservitz, George B.; Ross, Robert N.; Rukstalis, Daniel B.; Sarosdy, Michael F.; Soloway, Mark S.; Thiel, Robert; Vogelzang, Nicholas J.; Hayden, Cheryl L.

doi:10.1016/s0022-5347(01)65569-1

Cited by 131 publications

(28 citation statements)

References 12 publications

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“…[5][6][7][8] Most of these markers appear to have a greater sensitivity than cytology, especially for detecting lower grade tumours, 9,10 although often at a cost of specificity. Therefore, few markers have become integrated into the routine surveillance of patients at risk for recurrent TCC.…”

Section: Introductionmentioning

confidence: 99%

A pilot study of urinary microRNA as a biomarker for urothelial cancer

Snowdon

Boag

Feilotter

et al. 2013

CUAJ

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Objective: MicroRNAs (miRNAs) are part of a class of small ribonucleic acid (RNAs). They are important regulatory molecules, involved in several cell processes, such as developmental timing, stem cell division and apoptosis. Dysregulated miRNAs have been identified in several human malignancies, including bladder cancer tissue samples, and may confer a "tumour signature" that can be exploited for diagnostic purposes. We report on a prospective pilot study investigating the diagnostic capability of miRNAs in the urine of patients with urothelial cancer. Methods: Voided urine samples were collected from patients with urothelial carcinoma just prior to bladder tumour resection, as well as age-matched healthy control patients. Pathology demonstrated both low-and high-grade cancer. Total RNA was isolated and quantitative reverse transcriptase-polymerase chain reaction was performed on the RNA extracts using primers for 4 miRNAs shown previously to be dysregulated in solid urothelial carcinomas with RNU6B as the endogenous control. Standard urine cytology was performed on all samples in a blinded fashion. Results: Two miRNAs of interest were dysregulated in the urine from cancer patients with miR-125b showing an average 10.42-fold decrease (p < 0.01) and miR-126 showing an average 2.70-fold increase (p = 0.30) in the cancer samples compared to the normal controls. The sensitivity and specificity of the cytology on the same urine samples were 50% and 80%, respectively. Using these 2 miRNAs only, a decision-tree prediction model was generated for a validation cohort of patients yielding a specificity of 100% and a sensitivity of 80%. Discussion: This preliminary study of candidate urinary miRNA in patients with low-and high-grade urothelial cancer demonstrated a significantly improved diagnostic accuracy over cytology. These results provide rationale for further studies on discovery and validation of candidate miRNAs in voided urine and may potentially lead to the development of a non-invasive and sensitive test for bladder cancer diagnosis and prognosis.

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Section: Introductionmentioning

confidence: 99%

A pilot study of urinary microRNA as a biomarker for urothelial cancer

Snowdon

Boag

Feilotter

et al. 2013

CUAJ

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“…While the usefulness of this test is still being investigated, preliminary reports suggest that it is at least as good as, and perhaps superior to, conventional urine cytology for diagnosing TCC. 33 " 35 Given the relative ease with which monoclonal antibodies can be produced, it is likely that additional NMP immunoassays and immunohistochemical stains will be developed for detecting tumor cells in serum, body fluids, needle aspiration specimens, and tissue sections. It is unclear whether there is sufficient tumor-type specificity of some NMPs to allow their use as biomarkers of specific tumors, as, for example, in the immunohistochemical evaluation of a metastatic tumor of an unknown primary site.…”

Section: Resultsmentioning

confidence: 99%

Nuclear Matrix Proteins and Their Potential Applications to Diagnostic Pathology

Hughes

Cohen

1999

Am J Clin Pathol

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A b s t r a c tPathologists have long recognized the importance of alterations in the size and shape of the cell nucleus as phenotypic markers of pathologic processes, such as cellular injury, cell death, and neoplastic transformation. In fact, the disciplines of diagnostic surgical pathology and cytopathology are largely based on the capacity of their practitioners to predict the biologic behavior of tissues or individual cells based on the observation of specific changes in nuclear morphologic features. This ability to identify abnormal nuclear structure, until very recently, was limited largely to the alterations that could be discerned through the light microscope. Even as advances in molecular biology and protein chemistry gave scientists the tools necessary to study the composition of the structural proteins of the nuclear envelope and nuclear matrix in much greater detail than that provided by the microscope, the importance of these proteins was largely underappreciated.Fortunately, as our understanding of gene regulation has increased, it has become clear that the proteins that constitute the nuclear matrix serve far more than a static structural function. We now know that the nuclear protein matrix is a dynamic family of proteins that has a vital role in such fundamental cell processes as steroid hormone binding, gene transcription, and protein translation. Moreover, as our understanding of the normal functions of the nuclear protein matrix has increased, so has our understanding of its role in abnormal cellular processes, most notably, neoplastic transformation. The nuclear protein matrix is now viewed as a potential target for diagnostic tests in patients with cancer and for anticancer therapies. It also is regarded as an important area of research for experimental pathologists who are interested in understanding how gene transcription is modulated during development, apoptosis, and tumorigenesis. As scientific interest in the nuclear matrix protein (NMP) complex intensifies, it is likely that these proteins will emerge from basic science laboratories and enter the domains of clinical and anatomic pathology in the form of

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“…Urinary cytology may be a useful method for the detection of bladder cancer, due to the non-invasive nature and high specificity of the procedure (90-95%); however, it has a rather low sensitivity (30-40%) (96). Therefore, many alternative methods have been presented to diagnose bladder cancer, such as the BTA test, BTA stat test and NMP22 (97)(98)(99). These methods have a higher sensitivity (50-70%) than cystoscopy, but the increased sensitivity comes at the cost of specificity (60-80%) (95).…”

Section: Urine Mirna Detection In Urological Cancermentioning

confidence: 99%

microRNA detection in feces, sputum, pleural effusion and urine: Novel tools for cancer screening (Review)

et al. 2013

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Abstract. microRNAs (miRNAs) are short non-coding RNA sequences that play important roles in the regulation of gene expression. They have significant regulatory functions in basic cellular processes, including differentiation, proliferation and apoptosis. miRNAs are differentially expressed in tumors, compared with normal tissues. Importantly, miRNAs are also stable and abundantly present in body fluids and feces. The high reproducibility, sensitivity and specificity of miRNAs in body fluids and feces enable miRNAs to be used as potential molecular markers for cancer screening. An increasingly large number of research studies have reported the role of miRNAs in this field. In the present review, we focused mainly on the application of detecting miRNAs in stool, sputum, pleural effusion and urine, to detect colon, lung and urological cancers, highlighting the role of miRNAs in early diagnosis and prognosis. IntroductionCancer is currently the most lethal human disease. Lung and colorectal cancers are the first and third most common types of cancers and the leading causes of cancer-related mortality worldwide (1). Bladder cancer, a urological cancer, is the second most common malignancy that involves the urinary system, and the clinical outcome is often poor once the tumor becomes invasive (2). Although much progress has been made in the prevention, early diagnosis and treatment of cancer, survival rates are still not optimistic, indicating that a more powerful method to detect cancer in the early stages is needed. Early detection of cancer has been reported to greatly improve both the survival rate and prognosis, suggesting that the key to oncotherapy may lie in early diagnosis (3-7). Thus, developing a method for the early detection of cancer is both important and necessary. Ideally, an early detection method would have high sensitivity, specificity and repeatability, and would be safe, affordable and acceptable to the patient as well.Traditional methods, such as colonoscopy (8), bronchoscopy (9) and cystoscopy (10), are used to detect colon cancer, non-small cell lung cancer (NSCLC) and bladder cancer, respectively. These methods have greatly benefited many individuals in the past and they are still used to diagnose cancer. However, their use has been hampered by their invasive nature, the manpower resources they require, their high cost and the discomfort they cause patients (11-13).Biological screening methods, including the fecal occult blood test (FOBT) for colon cancer; sputum cytology for NSCLC (14); and the bladder tumor antigen (BTA test), BTA stat test, nuclear matrix protein 22 (NMP22), and urinary cytology for bladder cancer, have also been applied in recent years. However, these methods each have a significant sensitivity (15,16) or specificity (13), but not both.As previously mentioned, these methods have drawbacks that prevent their wide application.

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Urinary Nuclear Matrix Protein as a Marker for Transitional Cell Carcinoma of the Urinary Tract

Abstract: NMP22 is a promising urinary tumor marker for monitoring transitional cell carcinoma. Nuclear matrix proteins are a new class of tumor markers that represent the basis for the development of assays with increased efficacy for the detection and treatment of cancer.

Cited by 131 publications

References 12 publications

A pilot study of urinary microRNA as a biomarker for urothelial cancer

A pilot study of urinary microRNA as a biomarker for urothelial cancer

Nuclear Matrix Proteins and Their Potential Applications to Diagnostic Pathology

microRNA detection in feces, sputum, pleural effusion and urine: Novel tools for cancer screening (Review)

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