A population-based study of immunohistochemical detection of p53 alteration in bladder cancer

Kelsey, Karl T.; Hirao, Tomoko; Schned, Alan R.; Hirao, Shuya; M.S., Tara Devi-Ashok; Nelson, Heather H.; Andrew, Angeline S.; Karagas, Margaret R.

doi:10.1038/sj.bjc.6601748

Cited by 50 publications

(37 citation statements)

References 17 publications

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“…In our work, there was a striking difference between the proportion of mutations found and the proportion of p53 inactivation (Table I). The concordance rate (i.e., percent agreement) between mutation and IHC nuclear accumulation has been reported to vary markedly, i.e., from 7-90%, [29][30][31][32][33][34][35][36][37][38] but is generally between 65-75% across studies, including our own. 31 Interestingly, the pattern of some of these results tends to go in different directions depending upon whether one evaluates mutations or IHC.…”

Section: Discussionmentioning

confidence: 98%

“…The concordance rate (i.e., percent agreement) between mutation and IHC nuclear accumulation has been reported to vary markedly, i.e., from 7-90%, [29][30][31][32][33][34][35][36][37][38] but is generally between 65-75% across studies, including our own. 31 Interestingly, the pattern of some of these results tends to go in different directions depending upon whether one evaluates mutations or IHC. The precise reason for this is unclear but could relate to the specific part of the gene inactivated, as our data suggest that the concordance rate is specific to certain exons.…”

Section: Discussionmentioning

confidence: 98%

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TP53 alterations and patterns of carcinogen exposure in a U.S. population‐based study of bladder cancer

Kelsey

Hirao

et al. 2005

Intl Journal of Cancer

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The molecular pathology of bladder cancer has been the subject of considerable interest, and current efforts are targeted toward elucidating the interrelationships between individual somatic gene loss and both etiologic and prognostic factors. Mutation of the TP53 gene has been associated with more invasive bladder cancer, and evidence suggests that TP53 mutation, independent of stage, may be predictive of outcome in this disease. However, there is no consensus in the literature that bladder carcinogen exposure is associated with inactivation of the TP53 gene. Work to date has been primarily hospital based and, as such, subject to possible bias associated with selection of more advanced cases for study. We examined exposure relationships with both TP53 gene mutation and TP53 protein alterations in a population-based study of 330 bladder cancer cases in New Hampshire. Tobacco smoking was not associated with TP53 alterations. We found a higher prevalence of TP53 inactivation (i.e., mutation and nuclear accumulation) among hair dye users (odd ratio [OR] 5 4.1; 95% confidence interval [CI] 1.2-14.7), and the majority of these mutations were transversions. Men who had ''at risk'' occupations were more likely to have mutated TP53 tumors (OR 5 2.9; 95% CI 1.1-7.6). There also was a relative absence of TP53 mutation (OR 5 0.4; 95% CI 0.0-2.9) and TP53 protein alterations (OR 5 0.6; 95% CI 0.3-1.4) in bladder cancers from individuals with higher arsenic exposure. Our data suggest that there is exposure-specific heterogeneity in inactivation of the TP53 pathway in bladder cancers and that integration of the spectrum of pathway alterations in population-based approaches (capturing the full range of exposures to bladder carcinogens) may provide important insights into bladder tumorigenesis. ' 2005 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

TP53 alterations and patterns of carcinogen exposure in a U.S. population‐based study of bladder cancer

Kelsey

Hirao

et al. 2005

Intl Journal of Cancer

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“…It is recognized that p53 gene alteration is one of the important pathways leading to high-grade urothelial carcinoma with p53 immunohistochemical expression seen in 27.2-66% of urothelial carcinomas. 33,34 Based on our study, osteoclast-like giant-cell carcinomas of the urothelial tract should be considered as variants of urothelial carcinoma. Evidence to support this conclusion are: (1) the presence of keratin positivity in the majority of cases; (2) association with conventional urothelial carcinoma; and (3) matched p53 positivity in both the mononuclear cells and the accompanying urothelial neoplasm.…”

Section: Osteoclast-like Giant-cell Neoplasms D Baydar Et Almentioning

confidence: 89%

Osteoclast-rich undifferentiated carcinomas of the urinary tract

2006

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Osteoclast-like giant-cell neoplasms of the urinary tract are rare. They are composed of ovoid or spindle-shaped mononuclear cells with evenly spaced osteoclast-like giant cells. Terminology, histogenesis, and biologic behavior of these tumors remain controversial. Six cases of osteoclast-like giant-cell neoplasms of the urinary tract were identified from the consultation files of two of the authors. Patients were all male and elderly (range 65-82), with the exception of one 39-year-old male. In all, 3/6 tumors developed in the bladder and 3/6 in the renal pelvis. Size ranged from 5 to 11 cm. One bladder and three renal pelvis tumors were high stage (pT3) at time of presentation. Adjacent to the osteoclast-like giant-cell neoplasm in the same specimen, all patients had urothelial carcinoma in situ and/or high-grade papillary urothelial carcinoma. Multinucleated cells had identical morphological and immunohistochemical properties of osteoclasts; positive for CD-68, LCA, CD51 and CD54, and negative for cytokeratins and EMA. Varying percentages of mononuclear cells expressed a-smooth muscle actin (4/6), desmin (1/6), S-100 (4/6), LCA (2/6) and CD68 (6/6). However, mononuclear cells were also positive for epithelial markers in 4/6 tumors (cytokeratins AE-1/AE-3, Cam 5.2, CK7 and/or EMA). p53 stained mononuclear tumor cells in three cases, paralleling the staining on the accompanying urothelial carcinoma. Ki-67 stained mononuclear tumor cells, but not osteoclast-like giant cells. Follow-up data were available in five cases. One patient developed recurrence of noninvasive urothelial carcinoma and is still alive. Four patients were dead due to disease within 15 months, three with distant metastases. The intimate association of these tumors with urothelial carcinoma along with their immunohistochemical profile supports an epithelial origin for the mononuclear cells and non-neoplastic reactive histiocytic lineage for the osteoclast-like giant cells.

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“…Owing to the high concordance rates for overall diagnosis (490%), we classified subjects based on the original pathologist's diagnosis; whereas tumour morphology, extent of disease and grade were based solely on the standardized histopathology re-review by the study pathologist. Immunohistochemical analysis of the tumours was carried out for TP53 using a monoclonal antibody (BioGenex, San Ramon, CA, USA), and scored for intensity and the percentage of tumour cells staining positively as markers of tumour severity, as the number of tumours having TP53 mutations increases with the degree of invasiveness of the tumour (Kelsey et al, 2004) and may represent an aetiologically distinct subgroup of tumours (Kelsey et al, 2005;Wallace et al, 2009). We obtained informed consent from each participant and all procedures and study materials were approved by the Committee for the Protection of Human Subjects at Dartmouth College.…”

Section: Interviewsmentioning

confidence: 99%

Glucocorticoid therapy and risk of bladder cancer

Dietrich

Schned²,

Fortuny

et al. 2009

Br J Cancer

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BACKGROUND: Use of immunosuppressive drugs post organ transplantation, and prolonged use of glucorticoids for other conditions have been associated with subsequent risk of certain malignancies, that is, skin cancers and lymphoma. There is evidence that the incidence of bladder cancer is also elevated among organ transplant recipients, however, it is unknown whether other groups of patients, that is, those taking oral glucocorticoids, likewise are at an increased risk. METHODS: In a population-based case -control study in New Hampshire, USA, we compared the use of glucocorticoids in 786 bladder cancer cases and in 1083 controls. We used unconditional logistic regression analysis to compute adjusted odds ratios (ORs) associated with oral glucocorticoid use. RESULTS: In our analysis, the risk of bladder cancer was related to a history of prolonged oral glucocorticoid use (OR ¼ 1.85, 95% CI ¼ 1.24 -2.76, adjusted for age, gender and smoking). Associations with oral glucocorticoid use were stronger for invasive tumours (OR ¼ 2.12, 95% CI ¼ 1.17 -3.85) and tumours with high (3 þ ) p53 staining intensity (OR ¼ 2.35, 95% CI ¼ 1.26 -4.36). CONCLUSION: Our results raise the possibility of an increased risk of bladder cancer from systemic use of glucocorticoids, and a potential role of immune surveillance in bladder cancer aetiology.

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A population-based study of immunohistochemical detection of p53 alteration in bladder cancer

Cited by 50 publications

References 17 publications

TP53 alterations and patterns of carcinogen exposure in a U.S. population‐based study of bladder cancer

TP53 alterations and patterns of carcinogen exposure in a U.S. population‐based study of bladder cancer

Osteoclast-rich undifferentiated carcinomas of the urinary tract

Glucocorticoid therapy and risk of bladder cancer

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