Immunohistochemical analysis of proliferating cell nuclear antigen, p53 protein and nm23 protein, and nuclear DNA content in transitional cell carcinoma of the bladder

Shiina, Hìroaki; Igawa, Mikio; Nagami, Haruhiko; Yagi, Hiroshi; Urakami, Shinji; Yoneda, Tatsuaki; Shirakawa, Hiroki; Ishibe, Tomoyuki; Kawanishi, Masahiro

doi:10.1002/(sici)1097-0142(19961015)78:8<1762::aid-cncr17>3.0.co;2-w

Cited by 39 publications

(13 citation statements)

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“…Our results are consistent with several studies [12,29-31] which showed a significantly inverse correlation between reduced nm23-H1 expression and disease staging, histopathologic differentiation, tumor size, high risk of metastasis and reduced OS. However, some reports showed a positive correlation between nm23-H1 expression and tumor grading, muscle invasion or proliferating cell nuclear antigen expression, implying a positive growth regulatory role for nm23-H1 in bladder carcinogenesis [13,31,32]. …”

Section: Discussionmentioning

confidence: 99%

“…The clinical relevance of the nm23-H1 as a metastasis suppressor for human cancers including bladder is still controversial. Some studies demonstrated that nm23-H1 is inversely correlated with tumor staging, histological differentiation and clinical outcome [11,12], others showed a positive relationship to histological grading and muscle invasion [13]. …”

Section: Introductionmentioning

confidence: 99%

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Clinical significance of altered nm23-H1, EGFR, RB and p53 expression in bilharzial bladder cancer

et al. 2009

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BackgroundClinical characterization of bladder carcinomas is still inadequate using the standard clinico-pathological prognostic markers. We assessed the correlation between nm23-H1, Rb, EGFR and p53 in relation to the clinical outcome of patients with muscle invasive bilharzial bladder cancer (MI-BBC).Methodsnm23-H1, Rb, EGFR and p53 expression was assessed in 59 MI-BBC patients using immunohistochemistry and reverse transcription (RT-PCR) and was correlated to the standard clinico-pathological prognostic factors, patient's outcome and the overall survival (OS) rate.ResultsOverexpression of EGFR and p53 proteins was detected in 66.1% and 35.6%; respectively. Loss of nm23-H1and Rb proteins was detected in 42.4% and 57.6%; respectively. Increased EGFR and loss of nm23-H1 RNA were detected in 61.5% and 36.5%; respectively. There was a statistically significant correlation between p53 and EGFR overexpression (p < 0.0001), nm23 loss (protein and RNA), lymph node status (p < 0.0001); between the incidence of local recurrence and EGFR RNA overexpression (p= 0.003) as well as between the incidence of metastasis and altered Rb expression (p = 0.026), p53 overexpression (p < 0.0001) and mutation (p = 0.04). Advanced disease stage correlated significantly with increased EGFR (protein and RNA) (p = 0.003 & 0.01), reduced nm23-H1 RNA (p = 0.02), altered Rb (p = 0.023), and p53 overexpression (p = 0.004). OS rates correlated significantly, in univariate analysis, with p53 overexpression (p = 0.011), increased EGFR (protein and RNA, p = 0.034&0.031), nm23-H1 RNA loss (p = 0.021) and aberrations of ≥ 2 genes. However, multivariate analysis showed that only high EGFR overexpression, metastatic recurrence, high tumor grade and the combination of ≥ 2 affected markers were independent prognostic factors.Conclusionnm23-H1, EGFR and p53 could be used as prognostic biomarkers in MI-BBC patients. In addition to the standard pathological prognostic factors, a combination of these markers (≥ 2) has synergistic effects in stratifying patients into variable risk groups. The higher is the number of altered biomarkers, the higher will be the risk of disease progression and death.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical significance of altered nm23-H1, EGFR, RB and p53 expression in bilharzial bladder cancer

et al. 2009

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“…Findings about the relationship between p53 overexpression and subsequent tumor recurrence or progression in superficial bladder carcinoma have been contradictory. Although some authors have shown an association of p53 overexpression with tumor progression,17 others have reported no association 18, 19. Mutations in the p53 gene are the most common genetic defect in human tumors.…”

Section: Discussionmentioning

confidence: 99%

Patterns of multiple recurrences of superficial (Ta/T1) transitional cell carcinoma of bladder and effects of clinicopathologic and biochemical factors

Yan

Andriole

Humphrey

et al. 2002

Cancer

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BACKGROUND Although multiple sequential recurrences are one of the most important characteristics of superficial transitional cell carcinoma (TCC) of the bladder, few studies have examined multiple sequential recurrence patterns and the clinicopathologic and biochemical factors associated with these patterns. METHODS Two hundred seventy superficial TCC bladder carcinoma patients were followed. Clinical, pathologic, and tumor marker (p53, MIB‐1, bcl‐2, c‐erb B‐2, and epidermal growth factor receptor) data were collected at baseline and during followup. The Kaplan‐Meier (KM) method was used to describe multiple recurrences. The Wei, Lin, and Weissfeld (WLW) marginal proportional hazards model was used to assess the effects of clinicopathologic and immunohistochemic factors on multiple recurrences. RESULTS Among the 270 patients, 126 (46.7%) had one or more recurrences, 38 (14.1%) had two or more recurrences, and 14 (5.2%) had three or more recurrences during the followup. The median times for the first, the second, and the third recurrences were 23 months, 15 months, and 13 months, respectively. In KM analysis, Stage T1, higher grades, and Ki‐67 stain positivity were associated with the first recurrence, and p53 stain positivity was marginally significant. Other markers were not significant. For the second recurrence, only p53 stain positivity was significant. In multivariate analysis (WLW method), stage was significantly associated with the first recurrence (risk ratio [RR] = 2.03), and Ki‐67 was marginally significant (RR = 1.49). For the second recurrence, only p53 positivity was statistically significant (RR = 2.73). CONCLUSIONS Among superficial TCC bladder carcinoma patients, multiple recurrences are common phenomena. The time for recurrence becomes shorter as the number of recurrences increases. In addition to tumor stage and grade, Ki‐67 can be used to identify patients at high risk for a first recurrence; and p53 can be used to identify patients at high risk for a second recurrence. Cancer 2002;95:1239–46. © 2002 American Cancer Society. DOI 10.1002/cncr.10822

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“…In urothelial carcinoma in situ and T1 and T1a urothelial carcinoma, an association between p53 overexpression and tumor progression has been reported, but other studies have not found this association. [21][22][23][24][25][26] The data regarding p53 protein content in inverted papilloma are limited. Two studies that examined p53 in inverted papillomas showed that most inverted papillomas had fewer than 30% p53 positive cells, but some neoplasms showed p53 staining similar to high grade in- vasive urothelial carcinomas; no clinical data were provided in these series.…”

Section: Discussionmentioning

confidence: 99%

Inverted urothelial papilloma

Cheville

Sebo

et al. 2000

Cancer

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Immunohistochemical analysis of proliferating cell nuclear antigen, p53 protein and nm23 protein, and nuclear DNA content in transitional cell carcinoma of the bladder

Abstract: The tumor growth fraction as assessed by PCNA immunostaining is an independently significant predictor for survival of patients with TCC of the bladder.

Cited by 39 publications

References 39 publications

Clinical significance of altered nm23-H1, EGFR, RB and p53 expression in bilharzial bladder cancer

Clinical significance of altered nm23-H1, EGFR, RB and p53 expression in bilharzial bladder cancer

Patterns of multiple recurrences of superficial (Ta/T1) transitional cell carcinoma of bladder and effects of clinicopathologic and biochemical factors

Inverted urothelial papilloma

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