Implications of p53 gene mutations on patient survival in transitional cell carcinoma of the bladder: A long-term study

Salinas-Sánchez, Antonio S.; Lorenzo-Romero, Juan G.; Giménez-Bachs, José M.; Sánchez-Sánchez, Francisco; Donate-Moreno, María J.; Rubio‐del‐Campo, Antonio; Hernández-Millán, Ibrahim; Segura-Martín, Miguel; Atienzar-Tobarra, Manuel; Escribano, Julio

doi:10.1016/j.urolonc.2007.07.011

Cited by 21 publications

(14 citation statements)

References 15 publications

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“…In the aspect of recurrence, many authors have reported that there is no statistically significant relationship between them, although the recurrence rate tends to be increased in patients with p53 mutation or altered p53 protein expression [25,26]. George et al and Salinas-Sánchez et al did find a significant relationship between these same variables [9,10]. In our study, p53 overexpression was related with a shorter recurrence-free survival in the univariate analyses (p=0.017) but not in the multivariate model.…”

Section: Discussionmentioning

confidence: 99%

Expression of Fibroblast Growth Factor Receptor 3 in the Recurrence of Non-Muscle-Invasive Urothelial Carcinoma of the Bladder

2010

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Purpose:The fibroblast growth factor receptor 3 (FGFR3) gene is known to be frequently mutated in noninvasive urothelial carcinomas of the bladder. In this study, we investigated the expression of FGFR3, Ki-67, and p53 in bladder cancers and the effects of expression on tumor recurrence. Materials and Methods: Fifty-five cases of primary bladder cancer were examined by immunohistochemistry. The relationship of these markers with various clinicopathological factors, including recurrence, was assessed. Results: Positivity for cytoplasmic FGFR3 (FGFR3-c) was associated with a lower cancer grade (p=0.022) and stage (p=0.011). Recurrence was more frequent in patients with a higher stage, negative FGFR3-c, and high Ki-67 expression. According to univariate analysis, predictors of recurrence-free survival included the following: age, stage, FGFR-c, Ki-67, and p53. However, none of these was independent from the other parameters in multivariate studies. Conclusions:The immunohistochemical expression of FGFR3 is not only one of the characteristic features of lower-grade and lower-stage urothelial carcinoma but also a possible marker in predicting disease recurrence.

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Section: Discussionmentioning

confidence: 99%

Expression of Fibroblast Growth Factor Receptor 3 in the Recurrence of Non-Muscle-Invasive Urothelial Carcinoma of the Bladder

2010

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“…CDKN2A and TP53 mutations have been shown to be of prognostic value in different tumor types. [13][14][15][16] For instance, in head and neck SCCs, mutations in the CDKN2A and TP53 gene are shown to have a negative effect on survival. 13,14,28 In CSCCs, the prognostic effect of these genes has not been explored yet.…”

Section: Discussionmentioning

confidence: 99%

“…The PM-PCR RHA method has previously been described in detail. 24,26 The method was designed for the identification of 25 established beta-PV types, namely genotypes 5,8,9,12,14,15,17,19,20,21,22,23,24,25,36,37,38,47,49,75,76, 80, 92, 93 and 96.…”

Section: Alpha-pv Detection and Genotyping By Spf 10 -Lipa 25mentioning

confidence: 99%

“…CDKN2A and TP53 mutations have been shown to have a prognostic effect in different tumor types. [13][14][15][16] In CSCC, the influence of …”

mentioning

confidence: 99%

“…CDKN2A and TP53 mutations have been shown to have a prognostic effect in different tumor types. [13][14][15][16] In CSCC, the influence of CDKN2A and TP53 mutations on survival has not been investigated yet. One of the purposes of this study is to investigate the role of these genes on survival in a group of metastatic CSCCs.…”

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confidence: 99%

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CDKN2A but not TP53 mutations nor HPV presence predict poor outcome in metastatic squamous cell carcinoma of the skin

Küsters‐Vandevelde

Leeuwen

Verdijk

et al. 2009

Intl Journal of Cancer

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Genetic alterations in metastatic cutaneous squamous cell carcinoma (CSCC) which might serve as prognostic biomarkers are not well investigated. We investigated the mutation status and protein expression of the CDKN2A (INK4a-ARF) and TP53 genes in metastatic CSCCs and correlated this with clinicopathological variables, HPV presence, and survival data. Sequence analysis was performed on formalin-fixed and paraffin-embedded tissue of 35 metastases and their primary tumors, and was correlated with immunohistochemical stainings for p53, p16 and p14. Beta-PV and alpha-PV DNA was detected using PCRbased assays. Kaplan-Meier and Cox regression methods were used for survival assessment. CDKN2A was mutated in 31% of the metastases and their primary tumors, while the TP53 gene was mutated in 51% of the metastases. P53 protein expression was significantly associated with missense type of mutations (p 5 0.002). No persistent HPV types were detected. CDKN2A mutations were significantly associated with disease-specific death (p 5 0.001). A significant difference was observed in disease-specific survival between patients with or without a CDKN2A mutation (p 5 0.010), while this was not the case for TP53. At univariate Cox's regression analysis tumor size (p 5 0.010), invasion depth (p 5 0.030) and CDKN2A mutations (p 5 0.040) were significantly related to shorter disease-specific survival. At multivariate Cox's regression only tumor size had an adverse effect on survival (p 5 0.002). In conclusion, our study indicates that the CDKN2A mutation status might be of prognostic value in metastatic CSCCs. In most cases, CDKN2A and TP53 mutations are early genetic events in CSCC tumorigenesis. The possible role of HPV in metastatic CSCC needs further exploration.Cutaneous squamous cell carcinoma (CSCC) is the second most common malignancy in Caucasians, after basal cell carcinoma, and its incidence is still rising. 1 Generally the risk of metastasis is reported up to 5%, while immunocompromised patients have a larger tendency to metastasize (5-10%). 1,2 The outcome of these patients once metastasized is poor, with a 5-year survival rate between 25 and 50%. 3,4 Genetic alterations in CSCCs which might serve as prognostic biomarkers are not well investigated.TP53 mutations are the most frequent genetic alterations in CSCC with incidences of up to 50%. 5,6 TP53 mutations are early events in skin carcinogenesis, with a similar mutation frequency of 50% in actinic keratosis, a precancerous skin lesion that potentially can progress to CSCC. 7 Mutations in the CDKN2A (INK4a-ARF) locus are reported in CSCC with frequencies ranging up to 24% in sporadic CSCC. [8][9][10] This gene maps to chromosome 9p21, which by alternative transcripts encodes for 2 cell cycle regulatory proteins, p16 INK4a (Exons 1a, 2 and 3) and p14 ARF (Exons 1b, 2 and 3). 10,11 The exact role of the CDKN2A gene in skin carcinogenesis is not well understood. Especially in metastatic CSCCs alterations in the CDKN2A gene have not been investigated. In a small previous stud...

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Urothelial Carcinoma in Situ

2012

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Implications of p53 gene mutations on patient survival in transitional cell carcinoma of the bladder: A long-term study

Cited by 21 publications

References 15 publications

Expression of Fibroblast Growth Factor Receptor 3 in the Recurrence of Non-Muscle-Invasive Urothelial Carcinoma of the Bladder

Expression of Fibroblast Growth Factor Receptor 3 in the Recurrence of Non-Muscle-Invasive Urothelial Carcinoma of the Bladder

CDKN2A but not TP53 mutations nor HPV presence predict poor outcome in metastatic squamous cell carcinoma of the skin

Urothelial Carcinoma in Situ

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