Systemic markers of oxidative status and colorectal adenomatous polyps.

PURPOSE: Oxidative damage has been implicated in carcinogenesis. We hypothesized that elevated systemic oxidative status would be associated with later occurrence of colorectal adenomatous polyps, a precursor of colorectal cancer. METHODS: We examined the prospective association between four systemic markers of oxidative status and colorectal adenomatous polyps within a nondiabetic subcohort of the Insulin Resistance Atherosclerosis Study (n = 425). Urine samples were collected from 1992 to 1994 and colorectal adenomas prevalence were assessed in 2002 to 2004. Oxidative status markers were assessed, which included four F(2)-isoprostanes (F(2)-IsoPs) from the classes III and IV: iPF2α-III, 2,3-dinor-iPF2α-III (a metabolite of iPF2α-III), iPF2α-VI, and 8,12-iso-iPF2α-VI. All biomarkers were quantified using liquid chromatography-tandem mass spectrometry. Prospective associations were assessed using multivariate logistic regression analysis. RESULTS: The adjusted odds ratio (OR) (95% confidence interval [CI]) for occurrence of colorectal adenomatous polyps and scaled to 1 SD of F(2)-IsoP distribution were 1.16 (95% CI, 0.88-1.50), 0.88 (95% CI, 0.63-1.17), 1.04 (95% CI, 0.80-1.34), and 1.16 (95% CI, 0.90-1.48) for iPF2α-III, iPF2α-VI, 8,12-iso-iPF2α-VI, and 2,3-dinor-iPF2α-III, respectively. CONCLUSIONS: The lack of association between F(2)-IsoPs and adenomatous polyps does not support the hypothesis that elevated oxidative status is associated with colorectal adenomatous polyp occurrence during a 10-year period of follow-up.

Detection of mutated K-ras DNA in urine, plasma, and serum of patients with colorectal carcinoma or adenomatous polyps.

Our previous studies demonstrated that urine contains DNA derived from the circulation and that this DNA originated, in part, from organ sites and tumors distal to the urinary tract. To explore the potential use of DNA from urine as compared to other body fluids as a source for circulating DNA for cancer detection, the DNA concentration and the frequency of detection of mutated Kristin-ras (K-ras) DNA in serum, plasma, and urine were examined. The concentration of DNA in the urine was similar to that in the serum, but the DNA concentration in plasma was significantly lower than in either urine or serum (P < 0.05). When DNA derived from 10 muL of body fluid was used in each mutation assay, the detection frequency of mutated K-ras DNA was comparable among serum, plasma, and urine. However, when DNA derived from 200 muL of body fluid was used, the incidence of detecting mutated K-ras DNA in urine was significant higher (95%) than in either serum (35%) or plasma (40%) (P < 0.0005), suggesting that inhibitory factors in serum/plasma may be more limiting than in urine. The use and practicality of urine as a source of circulating DNA for cancer detection are discussed.

Detection of a K-ras mutation in urine of patients with colorectal cancer.

We previously demonstrated that human urine contains small, 150 to 250 nucleotide-sized, soluble DNA derived from the circulation, which may be useful in the detection of colorectal cancer. In this report we have determined the stability of DNA in urine and have found that the half-life time interval of this small, fragmented DNA is at least 4 hours post collection. We further compared, in a blinded study, the frequency of detecting mutated K-ras sequence in DNA isolated from plasma and urine derived from individuals who have either a colorectal carcinoma (CRC), or adenomatous polyps that contain a mutation in codon 12 of the K-ras proto-oncogene. There was an 83% concurrence of mutated DNA detected in urine and its corresponding disease tissue from the same individuals, when paired urine and tissue sections from 20 patients with either CRC or adenomatous polyps were analyzed for K-ras mutation. However, only a 56% concurrence was observed when the matched plasma specimens were tested from these 20 patients. These results suggest that urine might be a better resource for detecting K-ras mutation in circulating DNA.

Human urine contains small, 150 to 250 nucleotide-sized, soluble DNA derived from the circulation and may be useful in the detection of colorectal cancer.

Human urine has been shown to possess submicrogram per milliliter amounts of DNA. We show here that DNA isolated from human urine resolves into two size categories: the large species, greater than 1 kb, being predominantly cell associated and heterogeneous in size, and the smaller, between 150 to 250 bp, being mostly non-cell associated. We showed that the low molecular weight class of urine DNA is derived from the circulation, by comparing the mutated K-ras sequences present in DNA isolated from tumor, blood, and urine derived from an individual with a colorectal carcinoma (CRC) containing a mutation in codon 12 of the K-ras proto-oncogene. In the urine, mutated K-ras sequences were abundant in the low molecular weight species, but far less abundant in the large molecular weight-derived DNA. Finally, the possibility that detection of mutant K-ras sequences in DNA derived from the urine correlates with the occurrence of a diagnosis of CRC and polyps that contain mutant K-ras was explored in a blinded study. There was an 83% concurrence of mutated DNA detected in urine and its corresponding disease tissue from the same individuals, when paired urine and tissue sections from 20 subjects with either CRC or adenomatous polyps were analyzed for K-ras mutation. The possibility that the source of the trans renal DNA is apoptotic cells, and the potential use of this finding for cancer detection and monitoring is discussed.

Prostatic epithelial polyp diagnosed in a bladder wash.

Prostatic epithelial polyps, also known as adenomatous polyps or papillary adenomas with prostatic type epithelium, are uncommon lesions. These lesions typically involve the adult male urethra, trigone, or bladder dome. Diagnosis is usually made by biopsy. Presence of clusters of benign columnar cells in urine cytologic material can suggest the presence of such polyps and must be included in the differential diagnosis.

Urinary cytologic findings in patients with benign and malignant adenomatous polyps of the prostatic urethra.

CONTEXT: Urethral adenomatous polyps with prostatic epithelium (also known as benign prostatic epithelial polyps [BPEPs]) are a documented cause of hematuria, dysuria, and hematospermia, conditions that may prompt cytologic evaluation of urine. DESIGN: The urine cytologic test findings in 5 cases of biopsy-proven BPEPs and in 1 case of prostatic ductal adenocarcinoma (PDA) that presented as a urethral polyp were retrospectively evaluated. Immunocytochemical stain for prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and high-molecular-weight cytokeratin (34betaE12) were used in evaluation of the lesions. RESULTS: In 4 of 5 cases of BPEPs, clusters of bland columnar cells with uniform, oval nuclei were seen. Positive immunostaining for PSA and PAP confirmed the prostatic origin of the clusters in 2 cases. One urine sample contained abundant goblet cells and extracellular mucin, consistent with intestinal metaplasia coexisting in the bladder biopsy specimen. The urine sample in the fifth case of BPEPs contained no columnar cells. The last case had multiple urine cytologic evaluations that demonstrated PSA-positive, malignant-appearing clusters of columnar cells. A biopsy specimen of the polyps was described as a high-grade prostatic intraepithelial neoplasm in adenomatous polyp. However, in this patient, PDA was diagnosed on transurethral resection of the prostate specimen 4 years after the initial urine cytologic test. CONCLUSION: Benign prostatic epithelial polyps should be considered in the differential diagnosis of clusters of columnar cells in urine cytologic testing. Cells with malignant nuclear features should instigate a careful search for a (prostatic) neoplasm, which may present as urethral polyps (e.g., PDA). Stains for PSA or PAP are useful adjuncts in differential diagnosis of this condition.