High levels of p53 protein expression do not correlate with p53 mutations in hepatocellular carcinoma

2004 ◽  
Vol 11 (6) ◽  
pp. 502-510 ◽  
Author(s):  
M. Anzola ◽  
A. Saiz ◽  
N. Cuevas ◽  
M. Lopez-Martinez ◽  
M. A. Martinez de Pancorbo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Expression ◽  
P53 Protein ◽  
P53 Mutations ◽  
P53 Protein Expression

High P53 Protein Expression Level Independent of Mutational Status Is An Adverse Prognostic Factor for Survival in Acute Myeloid Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1490-1490 ◽  
Author(s):  
Alfonso Quintás-Cardama ◽  
Yi Hua Qiu ◽  
Sean Post ◽  
Steven M. Kornblau
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
Myeloid Leukemia ◽  
P53 Protein ◽  
P53 Mutations ◽  
P53 Expression ◽  
The Poor ◽  
P53 Protein Expression ◽  
Mutational Status ◽  
Acute Myeloid

Abstract Abstract 1490 Background: The tumor suppressor p53 is frequently mutated in human cancer, including acute myeloid leukemia (AML). In AML, p53 mutations have been associated with poor risk cytogenetics (i.e. complex karyotype, −5/−7). However, the function of p53 can also be compromised by protein stabilization and/or expression. The implications of p53 protein expression have not been studied in AML. Methodology: We assessed p53 expression by high-throughput reverse phase protein array (RPPA) technology in 511 pts (719 samples). Eleven CD34+ bone marrow (BM) and 10 normal peripheral blood (PB) lymphocyte samples were used as controls. Samples were printed as 5 serial 1: 2 dilutions in duplicate using an Aushon 2470 Arrayer. Mutational status was determined by Sanger sequencing of exons 5 through 9 of the p53 gene. Results: Paired PB- and BM-derived AML samples expressed similar p53 levels (p=0.25). A trend towards higher p53 expression at relapsed was observed among 47 paired diagnosis/relapse samples (p=0.07). Cases of AML-M3 and –M6 exhibited higher expression of p53 than other FAB subtypes. p53 expression directly correlated with age (p=0.01) and CD34 (p=0.001) and inversely correlated with WBC (p=0.007), BM (p=0.0001) and PB (p=0.0001) blasts, platelets (p=0.007), HLA-DR (p=0.01), CD19 (p=0.02), and survival (p=0.01). High p53 (p53high) expression level was more associated with unfavorable cytogenetics than with favorable or intermediate cytogenetics (p=0.00001). When all cytogenetic abnormalities were considered, pts with −5 had the highest levels of p53 (p=0.00001). Pts with RAS mutations, but not those with FLT3-ITD, NPM1, or IDH1/2, had lower levels of p53 protein. When pts were divided according to the level of p53 protein expression p53high was associated with lower complete remission (CR) rates (51% vs 56%; p=??) and higher relapsed rates (82% vs 62%; p=??). The median overall survival (OS) of pts with p53high and p53low were 29.8 vs. 51 wks (p=0.009). Most cases with p53high had unfavorable cytogenetics and the effect on OS was predominantly seen in that subpopulation with p53high and p53low pts living a medina of 23.4 vs. 36 wks (p=0.07), respectively. In order to determine whether the poor outcomes associated with p53high were due to the presence of a higher rate of p53 mutations among pts with p53high, we determined the p53 mutational status of 55 pts. p53high was highly correlated with the presence of p53 mutations as the latter were detected in 17/40 pts with p53high but in only 1/16 pts with p53low. Importantly, the presence of p53high, both in the presence (29 wks) or in the absence (24 wks) of p53 mutations, was associated with significantly worse overall survival compared with pts with p53low (56 wks; p=0.05, Figure 1). Multivariate analysis indicated that p53 is a significant independent risk factor for survival in AML. The final model included: age (p=0.000001), favorable cytogenetics (0.01), unfavorable cytogenetics (p=0.00001), WBC (p=0.0005), albumin (p=0.0003), FLT3-ITD (P=0.04), and P53 (P=0.02). p53high was positively correlated with p53pSER15 (p=0.00001), Rbp807p811 (p=0.0002), c-MET (p=0.01), FoxO3a (p=0.004), KIT (p=0.001), p38p180p182 (p0.02), BAD (p=0.0001), cleaved PARP (p=0.002), cleaved PARP (p=0.01), TCF4 (p=0.02), fibronectin (p=0.02), and hsp70 (p=0.003), and negatively with AKTp473 (p=0.01), ERK (p=0.002), mTOR (p=0.005), PI3Kp85 (p=0.002), PKCδ (p=0.00002), GAB2 (p=0.00005), beclin (p=0.007), JMJD6 (p=0.001), Gata3 (p=0.02), p21 (p=0.01), and Mdm2 (p=0.001). Conclusions: Our results suggest that high levels of p53 protein constitute a powerful marker of short survival in AML. This effect is independent of p53 mutational status. The poor outcome of pts with high level of expression of p53 in the absence of p53 mutations suggests that the p53 pathway may be functionally perturbed in a much higher proportion of pts with AML than previously recognized. These data support the use of p53 protein expression levels in prognostication and in the development of targeted therapeutics. Disclosures: No relevant conflicts of interest to declare.

p53 protein expression in patients with hepatocellular carcinoma from the high incidence area of Guangxi, Southern China

1997 ◽  
Vol 121 (2) ◽  
pp. 203-210 ◽  
Author(s):  
Guozhong Qin ◽  
Jianjia Su ◽  
Yaoyu Ning ◽  
Xiaoxian Duan ◽  
Dan Luo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Expression ◽  
Southern China ◽  
P53 Protein ◽  
P53 Protein Expression ◽  
High Incidence ◽  
High Incidence Area

Aberrant p53 protein expression and function in a panel of hematopoietic cell lines with different p53 mutations

2009 ◽  
Vol 82 (4) ◽  
pp. 301-307 ◽  
Author(s):  
Shimeru Kamihira ◽  
Chiharu Terada ◽  
Daisuke Sasaki ◽  
Katsunori Yanagihara ◽  
Kunihiro Tsukasaki ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Lines ◽  
P53 Protein ◽  
Hematopoietic Cell ◽  
P53 Mutations ◽  
P53 Protein Expression ◽  
And Function ◽  
Hematopoietic Cell Lines

Lack of Prognostic Significance of p53 and K-ras Mutations in Primary Resected Non–Small-Cell Lung Cancer on E4592: A Laboratory Ancillary Study on an Eastern Cooperative Oncology Group Prospective Randomized Trial of Postoperative Adjuvant Therapy

2001 ◽  
Vol 19 (2) ◽  
pp. 448-457 ◽  
Author(s):  
Joan H. Schiller ◽  
Sudeshna Adak ◽  
Richard H. Feins ◽  
Steven M. Keller ◽  
Willard A. Fry ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Protein Expression ◽  
Small Cell Lung Cancer ◽  
P53 Protein ◽  
Statistical Significance ◽  
Small Cell ◽  
P53 Mutations ◽  
Small Cell Lung ◽  
Ras Mutations ◽  
P53 Protein Expression

PURPOSE: To determine the prognostic and predictive significance of p53 and K-ras mutations in patients with completely resected non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomized preoperatively to receive adjuvant postoperative radiotherapy (Arm A) or radiotherapy plus concurrent chemotherapy (Arm B). p53 protein expression was studied by immunohistochemistry (IHC) and p53 mutations in exons 5 to 8 were evaluated by single-strand conformational analysis. K-ras mutations in codons 12, 13, and 61 were determined using engineered restriction fragment length polymorphisms. RESULTS: Four hundred eighty-eight patients were entered onto E3590; 197 tumors were assessable for analysis. Neither presence nor absence of p53 mutations, p53 protein expression, or K-ras mutations correlated with survival or progression-free survival. There was a trend toward improved survival for patients with wildtype K-ras (median, 42 months) compared with survival of patients with mutant K-ras who were randomized to chemotherapy plus radiotherapy (median, 25 months; P = .09). Multivariate analysis revealed only age and tumor stage to be significant prognostic factors, although there was a trend bordering on statistical significance for K-ras (P = .066). Analysis of survival difference by p53 by single-stranded conformational polymorphism and IHC, interaction of p53 and K-ras, interaction of p53 and treatment arm, nodal station, extent of surgery, weight loss, and histology did not reach statistical significance. CONCLUSION: p53 mutations and protein overexpression are not significant prognostic or predictive factors in resected stage II or IIIA NSCLC. K-ras mutations may be a weak prognostic marker. p53 or K-ras should not be routinely used in the clinical management of these patients.

Analysis of p53 Protein Expression in Hepatocellular Carcinoma

2016 ◽  
Vol 25 (3) ◽  
pp. 345-349 ◽  
Author(s):  
Florin Graur ◽  
Luminita Furcea ◽  
Emil Mois ◽  
Andrei Biliuta ◽  
Aliz-Timea Rozs ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Hepatitis B ◽  
Protein Expression ◽  
P53 Protein ◽  
Tumour Size ◽  
Study Group ◽  
Chi Square ◽  
Altered Expression ◽  
P53 Protein Expression

Background & Aims: Hepatocellular carcinoma (HCC) has a growing incidence and studies regarding the risk factors or pathogenesis for this type of carcinoma benefit special interest. This study evaluates the correlations between p53 protein expression and clinical and laboratory factors in patients withHCC. Methods: The study group included 76 patients diagnosed with HCC, either by biopsy or after surgical resection (with curative intent). Immunohistochemistry for p53 protein assessment was performed in all patients. Correlations between the protein 53 expression and age, tumour size, viral infection, liver cirrhosis were performed using the chi-square test (Pearson‘s chi-square) together with the contingency coefficient Kendall‘s coefficient in the tau-b form. Results: In the study group, 51 patients were male (67%) and 25 female (33%). Cirrhosis due to hepatitis virus B or C infection (in a proportion of 63% of the study group) was not significantly associated with the presence of HCC. Altered expression of p53 protein was observed in 69 patients (91%). The relationship between p53 protein expression and patient sex (p=0.067), age (p=0.531), tumour size (p=0.270), presence of hepatitis B and C viral infections (p=0.7), and of liver cirrhosis (p=0.511) was not statistically significant. Conclusion: The p53 protein expression was not significantly associated with the demographic characteristics of the patients, tumour size, presence of viral B and C infections or liver cirrhosis. Abbreviations: HBV: hepatitis B virus; HCV: hepatitis C virus; HCC: hepatocellular carcinoma; TP53: tumour protein p53; MDR: multi-drug resistance gene.

scholarly journals 54 Prognostic value of p53 protein expression in breast cancer

2020 ◽  
Author(s):  
S Ben Slama ◽  
D Bacha ◽  
A Ben Amor ◽  
A Halouani ◽  
A Lahmar
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Prognostic Value ◽  
P53 Protein ◽  
P53 Protein Expression

p53 protein expression in sequential biopsies of oral dysplasias and in situ carcinomas

1995 ◽  
Vol 24 (1) ◽  
pp. 18-22 ◽  
Author(s):  
J. A. Regezi ◽  
R. J. Zarbo ◽  
E. Regev ◽  
S. Pisanty ◽  
S. Silverman ◽  
...  
Keyword(s):  
Protein Expression ◽  
P53 Protein ◽  
P53 Protein Expression
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