PubMed Health⌕ Search

Biomedical subjects

Hagen Blaszyk

Publications and source records attributed to Hagen Blaszyk.

At least 37 records · Page 2Linked to original sources
PubMed2005

Hepatic copper in patients receiving long-term total parenteral nutrition.

GOALS: To assess the possibility of iatrogenic hepatic copper overload in adult patients on long-term total parenteral nutrition (TPN). BACKGROUND: TPN predisposes to hepatic copper accumulation through disturbances of the enterohepatic bile acid pool, but iatrogenic copper overload through TPN solutions may occur as well. STUDY: Quantitative hepatic copper and multiple clinical, biochemical, and histopathologic parameters were compared between patients with long-term TPN associated liver disease (n = 28) and patients with drug-induced cholestatic liver disease (n = 10). RESULTS: Eighty-nine percent of TPN patients and all controls had mildly elevated hepatic tissue copper, but 29% of TPN patients had levels above the diagnostic threshold for Wilson's disease. Quantitative hepatic copper correlated positively with serum aspartate aminotransferase (P = 0.001, r = 0.59), total bilirubin (P < 0.001, r = 0.65), and direct bilirubin (P < 0.001, r = 0.63) in TPN patients, but not in controls. The amount of hepatic copper did not correlate with the duration of TPN (median, 1.9 years; range, 0.3-18.0 years) or serum copper levels. TPN patients with significant cholestasis accumulated more copper than patients with no or only minimal cholestasis (P = 0.002). CONCLUSIONS: Significant hepatic copper overload in TPN patients occurs through chronic cholestasis in TPN-associated liver disease and is independent from the total duration of TPN. Iatrogenic copper overload through trace elements in TPN solutions does not seem to be a significant factor.

Adolescent↗
PubMed2005

Benign fibroblastic polyp of the colorectum.

GOALS: We present the clinicopathologic features, endoscopic appearance, and ultrastructure of a newly described mesenchymal polyp of the colorectum, termed benign fibroblastic polyp. STUDY: A total of 4 cases from our institution are analyzed using routine histopathology, immunohistochemistry, and electron microscopy, and compared with the original series of 14 cases previously described in the pathology literature. RESULTS: Benign fibroblastic polyps appear endoscopically throughout the colorectum as submucosal lesions with a hyperplastic surface component. These lesions are histologically and ultrastructurally distinct, but overlap with other mesenchymal polyps warrants additional immunohistochemical studies for definitive classification. CONCLUSIONS: Benign fibroblastic polyps of the colorectum comprise a recently described distinct entity of mesenchymal polyps that appear to follow an indolent clinical course. Their etiology is uncertain but may be linked to an exuberant tissue response following mucosal injury. Gastroenterologists should be aware of this new entity that will be increasingly diagnosed by pathologists.

Actins↗
PubMed2005

Histologic variation of grade and stage of non-alcoholic fatty liver disease in liver biopsies.

BACKGROUND: Sampling error regarding disease grade and stage has been ascribed to needle liver biopsies in patients with chronic liver disease. Although several studies evaluating sampling error in liver biopsies exist, none have investigated this phenomenon in patients with non-alcoholic fatty liver disease (NAFLD). This study aims to determine the rate and extent of sampling error in liver biopsies obtained from patients undergoing Roux-en-Y gastric bypass (RYGBP) surgery for morbid obesity. METHODS: 10 morbidly obese patients underwent simultaneous liver biopsies from the right and left hepatic lobes during an open examination preceding the RYGBP procedure. The biopsies were subsequently randomly evaluated and then blindly re-evaluated by a liver pathologist. Degrees of inflammatory activity and fibrosis were determined and scored for each sample using a semi-quantitative system with 3 grades and 4 stages. RESULTS: No grading differences were observed, and 3 patients (30%) had a difference of at least 1 stage between the right and left lobes. One patient had a 2-stage difference in paired samples, with significantly different biopsy sizes and number of portal tracts. Blinded histologic re-evaluation did not result in grading or staging scores that differed from the original evaluation. CONCLUSIONS: Liver biopsy samples taken from the right and left hepatic lobes showed similar grades of disease activity, but differed in histopathologic staging in 30% of the NAFLD patients. Obtaining an adequately sized biopsy (>1.0 cm in length with >10 portal tracts) greatly reduces sampling error.

Adult↗
PubMed2005

Multitarget FISH and LOH analyses at chromosome 3p in non-small cell lung cancer and adjacent bronchial epithelium.

Multitarget fluorescence in situ hybridization (FISH; LAVysion, Vysis, Downers Grove, IL) targeting chromosomes 6p11-q11, 7p12, 8q24, and 5p15.2 was compared with results of microsatellite studies at chromosome 3p to identify molecular changes associated with tobacco use and tumor development in non-small cell lung cancer (NSCLC). Analyses were performed on 26 NSCLCs and matched benign bronchial epithelium; samples from 10 patients without NSCLC served as control samples. Significant molecular differences between tumor tissue and corresponding benign bronchi were found using FISH (P = .001) and loss of heterozygosity (LOH) analysis (P = .031). Bronchial epithelium from patients with NSCLC was genetically different from epithelium from patients without NSCLC in FISH analysis (P = .025). Receiver operating characteristic curve analysis revealed an optimal cutoff value of 5% atypical cells for bronchial epithelium. There was no statistical correlation with the patient's smoking history, and LOH analysis of bronchi did not differentiate between patients with and without NSCLC. Multicolor FISH analysis is able to detect a tumor-associated molecular field effect in bronchi adjacent to NSCLC.

Adult↗
PubMed2005

High-throughput tissue microarray analysis of COX2 expression in urinary bladder cancer.

To investigate whether protein expression of cyclooxygenase 2 (COX2) is associated with tumor phenotype, immunohistochemical alterations, and clinical outcome in urinary bladder cancer (BC). Tissue microarrays (n = 776) were used to analyze COX2, P53 and the Ki-67 labeling index immunohistochemically. A monoclonal mouse antibody was used after heat-induced antigen retrieval. COX2 expression was scored semiquantitatively (0-3+). COX2 expression was detected in 60% (368/617) of urothelial BC. Positive COX2 staining was seen in 77.8% (140/182) of muscle invasive urothelial BC, compared to 35% (7/20) of muscle invasive squamous cell carcinomas (p < 0.001). COX2 protein expression was associated with advanced tumor stage (p < 0.0001), high-grade histology (p < 0.0001), solid growth pattern in invasive BC (pT1-4, p = 0.02), high Ki-67 labeling index (p < 0.0001), and positive P53 IHC (p < 0.001). COX2 expression was not associated with survival, recurrence, and progression in clinically relevant subgroups (pTa, pT1, pT2-4). Expression of COX2 is common in advanced BC with poor prognostic characteristics, supporting efforts to initiate clinical trials on the efficacy of COX2 inhibitors in the adjuvant treatment of high-risk urinary BC.

Aged↗
PubMed2004

Microsatellite instability predicts poor short-term survival in patients with advanced breast cancer after high-dose chemotherapy and autologous stem-cell transplantation.

PURPOSE: The purpose is to define molecular prognostic factors in patients with advanced breast cancer treated with high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). EXPERIMENTAL DESIGN: Thirty-nine patients with breast cancer and extensive lymph node (level III) and/or systemic metastases from a prospective single-center study of sequential HDCT/ASCT were studied. Microsatellite analysis was performed after laser microdissection using 15 markers selected for sensitive detection of microsatellite instability (MSI) in breast cancer. Exons 5-9 of the P53 gene were directly sequenced. Expression of P53, HER-2/neu, and the mismatch repair proteins hMSH2 and hMLH1 was evaluated by immunohistochemistry. RESULTS: MSI of at least three markers was detected in 13 of 39 patients (33%) and was predominantly found at tetranucleotide markers. All MSI-positive tumors showed normal expression of hMSH2 and hMLH1. Complete sequence analysis of exons 5-9 of the P53 gene was successful in 34 cases; 18% (n = 6) revealed a mutation. Overexpression of HER-2/neu and P53 was observed in 7 (22%) and 12 (46%) of 26 evaluated cases, respectively. The presence of MSI strongly correlated with shorter overall survival (OS; P = 0.0004) and progression-free survival (PFS; P = 0.02). None of the other investigated clinical or molecular factors correlated with OS in univariate analyses, with the exception of menopausal status and previous adjuvant chemotherapy. Testing various multivariate Cox regression models, MSI remained a highly significant, independent, and adverse risk factor for OS. CONCLUSIONS: MSI is frequent in advanced breast cancer and could be an indicator of chemotherapy resistance and poor prognosis in breast cancer patients treated with HDCT/ASCT.

Adult↗
PubMed2004

Gene expression profiling of colorectal cancer and metastases divides tumours according to their clinicopathological stage.

Gene expression profiling of matched colorectal carcinomas and metastases could reveal key molecular events involved in tumour progression and metastasis. Expression profiles have been created from 25 colorectal carcinomas (CRCs, pT1-4), corresponding normal colonic mucosa, and 14 liver metastases using cDNA arrays containing 1176 cancer-related genes (Clontech). Hierarchical clustering clearly distinguished carcinomas from non-cancerous tissues, separated tumours into high-stage (pT4 and extensive lymph node or distant metastases) and low-stage (< or =pT3) groups, and correlated with the histopathological classification in 87% (33/38 cases). Most primary tumours and matched liver metastases clustered on terminal branches of the dendrogram. Statistical analysis (Mann-Whitney U-test) revealed 40 tumour-specific genes (29 up-regulated, 11 down-regulated) which allowed identification of malignant tissue samples by cluster analysis. A specific expression signature in matching metastases was not found, but a set of 23 classifier genes with statistically significant expression patterns in high- and low-stage tumours was identified. These genes may represent important targets in colorectal carcinogenesis and might provide useful clinicopathological tools in the management of colorectal cancer.

Adenocarcinoma↗
PubMed2004

Deletions of chromosome 8p and loss of sFRP1 expression are progression markers of papillary bladder cancer.

Many molecular alterations are known to occur in urothelial carcinoma of the bladder, but their significance for tumor progression is poorly understood. Deletions of chromosome 8p are frequently found in several tumor types and are often associated with progressive disease. In all, 99 bladder tumors were screened for deletions at 8p using loss of heterozygosity (LOH) and multicolor fluorescence in situ hybridization FISH analyses. Allelic loss on chromosome 8p in at least one marker was found in 25/99 (25%) tumors. There was a significant correlation of 8p deletions with invasive tumor growth and a highly significant association with papillary growth pattern in patients with invasive disease. cDNA array analyses revealed that secreted Frizzled-related protein 1 (sFRP1), an antagonist of Frizzled receptors and Wnt pathway activation on chromosome 8p12-11.1, is frequently downregulated in bladder cancer. To investigate sFRP1 as a candidate for a putative progression-related gene on 8p, urothelial cell lines and primary urothelial carcinomas were screened for sFRP1 expression using quantitative real-time PCR, Northern blot, immunofluorescence and immunohistochemistry (IHC). Of the investigated bladder cancers, 38% showed loss of sFRP1 expression by quantitative RT-PCR. Evaluation of the protein expression by IHC using tissue microarrays containing 776 bladder cancers revealed loss or strong reduction of sFRP1 expression in 66% of cases. SFRP1 loss was associated with higher tumor stage and grade and shorter overall survival. In addition, loss of sFRP1 was an independent indicator of poor survival in patients with papillary but not with muscle invasive bladder cancer. There were neither mutations in the coding region of sFRP1 nor homozygous deletions at 8p12-11.21. However, promoter methylation was detected using methylation-specific PCR in 29% of cases. In conclusion, we could show a close correlation of chromosome 8p deletions and progression of papillary bladder tumors. The sFRP1 gene on chromosome 8p12-11.1 could be a candidate gene for the predicted, progression-related tumor suppressor gene in bladder cancer and could contribute to urothelial carcinogenesis.

Biomarkers, Tumor↗
PubMed2004

Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome.

BACKGROUND & AIMS: Serotonin (5-HT) is a critical signaling molecule in the gut. 5-HT released from enterochromaffin cells initiates peristaltic, secretory, vasodilatory, vagal, and nociceptive reflexes. Despite being pathophysiologically divergent, ulcerative colitis (UC) and irritable bowel syndrome (IBS) are both associated with clinical symptoms that include alterations in the normal patterns of motility, secretion, and sensation. Our aim was to test whether enteric 5-HT signaling is defective in these disorders. METHODS: Rectal biopsy specimens were obtained from healthy controls and patients with UC, IBS with diarrhea (IBS-D), and IBS with constipation (IBS-C). Key elements of 5-HT signaling, including measures of 5-HT content, release, and reuptake, were analyzed with these samples. RESULTS: Mucosal 5-HT, tryptophan hydroxylase 1 messenger RNA, serotonin transporter messenger RNA, and serotonin transporter immunoreactivity were all significantly reduced in UC, IBS-C, and IBS-D. The enterochromaffin cell population was decreased in severe UC samples but was unchanged in IBS-C and IBS-D. When 5-HT release was investigated under basal and mechanical stimulation conditions, no changes were detected in any of the groups relative to controls. CONCLUSIONS: These data show that UC and IBS are associated with similar molecular changes in serotonergic signaling mechanisms. While UC and IBS have distinct pathophysiologic properties, these data suggest that shared defects in 5-HT signaling may underlie the altered motility, secretion, and sensation. These findings represent the first demonstration of significant molecular alterations specific to the gut in patients with IBS and support the assertion that disordered gastrointestinal function in IBS involves changes intrinsic to the bowel.

Adult↗
PubMed2004

Distinct secreted Frizzled receptor protein 1 staining pattern in patients with hyperplastic polyposis coli syndrome.

CONTEXT: Patients with hyperplastic polyposis coli syndrome are thought to harbor precursor lesions of a proposed hyperplasia-carcinoma pathway in colorectal cancer, but morphologic recognition of such lesions remains difficult. Hypermethylation of the secreted Frizzled receptor protein 1 gene on chromosome 8p12 is one of the earliest molecular alterations in colorectal carcinogenesis, potentially disrupting the Wnt signaling cascade of cellular growth control. OBJECTIVE: To determine if hyperplastic polyps from patients with hyperplastic polyposis coli syndrome show a distinct immunohistochemical expression pattern for mismatch repair proteins and secreted Frizzled receptor protein 1 compared to their sporadic counterparts. DESIGN: Immunohistochemical studies (secreted Frizzled receptor protein 1, 3 mismatch repair proteins, and p53) were performed on 23 hyperplastic polyps, 6 synchronous colon cancers, and normal colonic mucosa from 6 patients with hyperplastic polyposis coli syndrome and were compared with studies of sporadic hyperplastic polyps obtained from 13 matched control subjects. RESULTS: The staining pattern for the mismatch repair proteins MLH-1, MSH-2, and MSH-6 did not differ between sporadic and syndromic hyperplastic polyps. In contrast, 52% of syndromic hyperplastic polyps showed a reproducible and distinct staining pattern for secreted Frizzled receptor protein 1 that was not seen in control specimens and that was associated with larger polyp size (P =.002) and location in the proximal colon (P =.01). CONCLUSIONS: Some hyperplastic polyps from patients with hyperplastic polyposis coli syndrome show a secreted Frizzled receptor protein 1 immunophenotype that could indicate alterations of cellular growth control. These findings may help identify precursor lesions in the proposed hyperplasia-carcinoma pathway of colorectal carcinogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2004

No evidence for mutation of B-RAF in urothelial carcinomas of the bladder and upper urinary tract.

Mutational activation of the MAP kinase pathway is frequently found in various cancers. Recently, activating mutations in the B-RAF gene, an important activator of this pathway, have been described in several tumor types including melanoma, colorectal and papillary thyroid cancer. The most frequent mutation in exon 15 (V599E), as well as several other mutations within exons 11 and 15 result in constitutive activation of the oncoprotein. In addition, a significant association between mismatch-repair (MMR) deficiency and the V599E mutation in colorectal tumors has been found. The aim of our study was to investigate B-RAF mutations in 121 urothelial carcinomas of the urinary bladder (ranging from pTaG1 to pT4aG3) and 27 tumors from the upper urinary tract (UUT), including 16 tumors of the renal pelvis and 11 tumors of the ureter). Twelve of 27 UUT tumors were MMR-deficient and showed microsatellite instability. The V599E mutation was screened for by allele-specific PCR (PASA) and exons 11 and 15 of B-RAF including intron-exon-boundaries were sequenced. Overall, 116/121 bladder tumors and 23/27 tumors of the UUT were successfully investigated by PASA. None of the tumors showed the V599E mutation. Sequence analysis of exons 11 and 15 was successful in 46 urothelial tumors (bladder, n=31; UUT, n=15). No mutations within the coding region of exons 11 and 15 and the intron-exon junctions were found. The most frequent alterations in the B-RAF gene do not seem to be involved in urothelial carcinogenesis, and there is no correlation between MMR-deficiency and B-RAF mutations in urothelial tumors.

Aged↗
PubMed2003

Urothelial carcinoma of the upper urinary tract: inverted growth pattern is predictive of microsatellite instability.

Urothelial carcinoma of the renal pelvis and ureter may develop as a manifestation of hereditary nonpolyposis colorectal cancer syndrome (HNPCC), a disorder characterized by mutation or inactivation of a number of DNA mismatch repair genes and detectable as microsatellite instability (MSI). Some urothelial carcinomas display areas of endophytic, or inverted, growth. In this study, urothelial cancers of the upper urinary tract (n = 132) from patients treated at 2 tertiary care centers were studied to identify an association between growth pattern and MSI. Thirty-five neoplasms were microsatellite unstable (26.5%), and MSI was more frequent in papillary lesions than in sessile urothelial cancers (P = .033). The amount of inverted growth was estimated as a percentage of the total tumor. The interobserver and intraobserver concordance in recognizing inverted growth was good, and 65.7% of microsatellite-unstable tumors exhibited at least 20% of an inverted growth component, compared with only 17.5% of microsatellite-stable tumors (P < .0001). In this series, inverted growth predicted MSI with a sensitivity and specificity of .82. Inverted growth in urothelial carcinomas of the upper urinary tract may serve as a marker lesion for MSI and may help identify patients who should be offered testing for HNPCC.

Adult↗
PubMed2003

Cancer of unknown primary: clinicopathologic correlations.

Cancer of unknown primary origin (CUP) accounts for 5-10% of all malignant tumors at presentation and remains the death certificate diagnosis in 0.5-5% of patients. We investigated CUP patients whose primary site remained unknown throughout the entire clinical course. We reviewed 9,436 consecutive autopsies performed between 1984 and 1999 at the Mayo Clinic, matched with 177,167 cancer patients treated in the same time period. Sixty-four patients who died of CUP underwent postmortem examination. Antemortem pathologic diagnoses were obtained in 57 patients, agreed with postmortem diagnoses in 98%, and included adenocarcinoma (n=44), undifferentiated carcinoma (n=7), squamous cell carcinoma (n=3), and others (n=3). Autopsy located the primary site in 35 patients (55%). Common primary sites were lung (n=8), the pancreaticobiliary (n=13) and GI tracts (n=9). Of 43 patients evaluated for tumor-specific therapy, only six received no further oncologic treatment and untreated patients survived a median of 57 (range 10-280) days, compared with 225 (range 19-1,129) days for patients treated with chemotherapy and/or radiotherapy (n=37). Our findings show that (1) autopsy studies provide a valuable tool for quality control in the setting of CUP, and (2) treated patients have a small but significant survival benefit.

Adenocarcinoma↗
PubMed2003

Hereditary nonpolyposis colorectal cancer syndrome in a patient with urothelial carcinoma of the upper urothelial tract.

Urothelial carcinoma of the upper urinary tract is relatively uncommon but may develop as a manifestation of the hereditary nonpolyposis colorectal cancer syndrome (HNPCC), which is characterized by mutations in a number of DNA mismatch repair genes and detectable as microsatellite instability or loss of the respective protein by immunostaining. No well-established screening test is available for urothelial carcinomas of the upper urinary tract, and little is known of the clinical impact of screening for HNPCC in patients with upper urinary tract cancer. We describe herein a patient with a urothelial carcinoma of the ureter and a strongly positive history of cancer, who was subsequently found to have HNPCC. Our findings reinforce the importance of obtaining a comprehensive history of cancer in patients with urothelial carcinoma of the renal pelvis and ureter. Subsequent identification of individuals with HNPCC enables the patient and at-risk relatives to benefit from targeted surveillance and management programs.

Colectomy↗
PubMed2003

Microsatellite instability at chromosome 8p in non-small cell lung cancer is associated with lymph node metastasis and squamous differentiation.

Genetic alterations at chromosome arm 8p are associated with advanced disease and poor patient outcome in several types of malignant tumors. We studied the frequency of microsatellite instability (MSI) and loss of heterozygosity (LOH) at chromosome 8p in early stage non-small cell lung cancer (NSCLC) of 47 patients with stage I or II disease (25 squamous cell carcinomas and 22 adenocarcinomas). Microsatellite analysis was performed after laser microdissection using 5 polymorphic tetranucleotide microsatellite markers and 4 dinucleotide markers at chromosome 8p. A pentanucleotide repeat marker at the chromosomal locus 17p13.1 (TP53.Alu) was also analyzed. Expression of the mismatch repair (MMR) proteins hMSH2, hMSH6 and hMLH1 was evaluated by immunohistochemistry. Microsatellite instability (MSI) in at least 2 markers was detected in 9 of 47 patients (19.1%) and was predominantly found at tetranucleotide repeats. Sixteen of 47 (34.0%) NSCLC demonstrated LOH at chromosome 8p. All MSI-positive tumors showed normal expression of the MMR proteins. The presence of MSI at chromosome 8p was associated with lymph node metastasis (p=0.02), squamous differentiation (8/25; 32%-p=0.03), and the presence of LOH at the p53 locus (p=0.06). None of the other investigated clinical, pathologic or molecular factors correlated with MSI. Our study showed that an elevated MSI at selected tetranucleotide sequences (EMAST) on chromosome 8p is frequent in early stage squamous cell carcinomas of the lung with lymphatic spread. The tetranucleotide marker panel used in this study was able to indicate lymph node metastasis and high risk disease in patients with resectable squamous cell lung cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Frequent microsatellite instability in sporadic tumors of the upper urinary tract.

Urothelial carcinoma of the renal pelvis and ureter may develop sporadically or as a manifestation of hereditary nonpolyposis colorectal cancer. The majority of hereditary nonpolyposis colorectal cancer is caused by mutation of the human DNA mismatch repair (MMR) genes and is detected by associated microsatellite instability (MSI). Seventy-three unselected urothelial carcinomas of the ureter and/or renal pelvis were screened for MSI using the National Cancer Institute-designated reference panel (plus BAT40). Instability of at least two microsatellite markers (MSI-high) was detected in 15 samples (21%). Immunohistochemical staining of the MMR proteins (hMSH2, hMLH1, or hMSH6) was absent in 13 of 15 (87%) MSI tumors, and alteration of coding sequence microsatellites (TGFbetaRII, Bax, hMSH3, and hMSH6) was found at frequencies of 7-33% in these samples. Tumors with MSI had significantly different clinical and histopathological features including higher prevalence in female patients, low tumor stage and grade, and a papillary and frequently inverted growth pattern. Our results suggest a molecular pathway of tumorigenesis that is similar to MMR-deficient colorectal cancers and consistent with the notion that the site distributions of hereditary or sporadic MSI-high tumors may reflect tissue-specific susceptibility to lesions processed by the MMR machinery.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Histologic-genetic mapping by allele-specific PCR reveals intraurothelial spread of p53 mutant tumor clones.

Common and clinically important features of urothelial carcinomas are multifocality and a high rate of recurrence. Molecular studies demonstrated that multifocal tumors are frequently composed of one tumor clone spreading throughout the urothelial tract. A combination of histologic and genetic mapping of cystectomy specimens from bladder cancer patients is a valuable tool to study bladder carcinogenesis and tumor cell spread by correlating urothelial morphologic features and defined genetic alterations. In the present study, the primary tumors of 14 cystectomy specimens were investigated for p53 protein overexpression by immunohistochemistry and p53 gene mutation by genomic sequencing. Seven tumors showed a strong nuclear staining for the p53 protein. In six of seven tumors, a p53 gene mutation was detected. Allele-specific PCR of defined p53 mutations was established in five of six cases with a p53 mutation. Subsequent screening of the entire urothelial lining of each cystectomy specimen by allele-specific PCR revealed p53-mutant cell clones in urothelial patches with carcinoma in situ and dysplasia, but also frequently in histomorphologically normal urothelium adjacent to the tumor. The pattern of tumor cell spread indicated a continuous intraurothelial growth of the p53-mutant clone. P53 immunohistochemistry visually confirmed the presence of mutant cells in most of these samples. We conclude that allele-specific PCR is a highly sensitive and reliable method for tracking specific p53 mutant clones in the urothelium. Moreover, the detection of p53-mutant cells in histologically normal or preneoplastic urothelial areas in four patients with invasive bladder cancer indicates an extensive intraurothelial tumor cell spread. The excellent correlation of immunohistochemically positive urothelial patches with the presence of a specific mutation highlights the biologic significance of p53-positive cells in the urothelium of tumor patients.

Aged↗