Diagnosis of Genito-Urinary Tract Cancer by Detection of Minichromosome Maintenance 5 Protein in Urine Sediments

Abstract

Elevated levels of Mcm5 in urine sediments are highly predictive of bladder cancer.

Diagnosis of oesophageal cancer by detection of minichromosome maintenance 5 protein in gastric aspirates

“…The sensitivity and specificity data are strikingly similar when comparing oesophageal cancer with genitourinary tract cancers. The areas under the ROC curve for oesophagus, bladder and prostate are all around 0.93 (Figure 1; Stoeber et al, 2002). It is likely that similar results will be obtained for other cancers arising from self-renewing tissues using this approach.…”

“…Maturation arrest and failure to engage correctly the differentiation programme, the hallmark of dysplastic precancerous lesions, is associated with aberrant expression of the MCM replication initiation factors Stoeber et al, 1999;Going et al, 2002;Stoeber et al, 2002). Importantly, aberrant expression of MCM proteins was identified in both squamous dysplasia and Barrett's glandular dysplasia, but not in Barrett's metaplastic oesophagus (Figure 3; Going et al, 2002).…”

“…Proteins of the minichromosome maintenance (MCM) family (minichromosome maintenance protein 2 -7, Mcm2 -7) play a critical role (DNA replicative helicase) in the initiation of DNA replication (Bell and Dutta, 2002). We have previously demonstrated that dysregulation of MCM proteins is an early event in epithelial carcinogenesis, resulting in exfoliation of MCM-positive tumour cells, and have used these novel biomarkers of growth in diagnostic screening applications for cervical and genitourinary tract cancer Stoeber et al, 1999;Stoeber et al, 2002). Moreover, we have shown that dysregulation of the DNA replication initiation pathway is an early event in oesophageal carcinogenesis with aberrant expression of MCM proteins occurring in both squamous dysplasia and glandular dysplasia complicating Barrett's oesophagus (Going et al, 2002).…”

The cell cycle and cancer

“…The detection of exfoliated MCM positive cells in body fluids (eg in urine, prostatic secretions, stool samples or gastro-oesophageal aspirates) or active sampling by swabbing or brushing (eg cervical smears or ERCP brushings for pancreaticobiliary tract sampling) provides a sensitive and specific method for the detection of premalignant and malignant lesions in a range of organ systems [39,[91][92][93][94][95][96][97][98]. For example, the immunostaining of cervical Pap smears for Mcm2-7 has potential to increase both the sensitivity and specificity of this error-prone test [39,[99][100][101].…”

“…An alternative method to detect MCM-positive tumour cells in patient samples is to use liquid-phase assays such as ELISA or DELFIA. Clinical studies using this approach have generated encouraging results for diverse tumour types, including the screening of urine sediments for detection of transitional cell carcinoma of the bladder and prostate cancer, and bile aspirates for pancreaticobiliary tract cancer [94,95,97,98]. An MCM-based cancer test (Figure 2) has therefore broad potential clinical utility in cancer detection, tumour surveillance, population screening, monitoring of therapeutic response and prognostication.…”