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

Khaled HM, Bahnassy AA, Raafat AA, Zekri AR, Madboul MS, Mokhtar NM - BMC Cancer (2009)

Bottom Line: 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 > or = 2 genes.In addition to the standard pathological prognostic factors, a combination of these markers (> or = 2) has synergistic effects in stratifying patients into variable risk groups.

View Article: PubMed Central - HTML - PubMed

Affiliation: Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt. khaled@internetegypt.com

ABSTRACT

Background: Clinical 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).

Methods: nm23-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.

Results: Overexpression 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 > or = 2 genes. However, multivariate analysis showed that only high EGFR overexpression, metastatic recurrence, high tumor grade and the combination of > or = 2 affected markers were independent prognostic factors.

Conclusion: nm23-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 (> or = 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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Kaplan-Meier analysis for cases of BBC. Overall survival is significantly lower in patients with: (a) increased EGFR expression, (b) p53 overexpression, (c) combined (nm23 -ve and EGFR +ve), (d) combined (nm23 -ve and p53 +ve),
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Figure 3: Kaplan-Meier analysis for cases of BBC. Overall survival is significantly lower in patients with: (a) increased EGFR expression, (b) p53 overexpression, (c) combined (nm23 -ve and EGFR +ve), (d) combined (nm23 -ve and p53 +ve),

Mentions: On univariate analysis there was a statistically significant correlation between reduced OS rates and tumor type (SCC) (p = 0.043), high tumor grade (p = 0.008), local recurrence (p = 0.0001) and distant metastasis (p = 0.0001). A borderline significance was reported between advanced disease stage (3b+4 vs 2+3a) and reduced OS. Similarly reduced OS rates was significantly associated with loss of nm23-H1 RNA (p = 0.021), increased EGFR protein (Figure 3a) and EGFR RNA expression (p = 0.034 &p = 0.025) and p53 overexpression (p = 0.011) (Figure 3b). The cumulative survival for cases with normal nm23-H1 RNA expression was 64.8% whereas it was 35.5% for cases with reduced/lost nm23-H1 RNA. Likewise, the cumulative survival for EGFR positive patients was 41.0% compared to 69.0% for EGFR negative patients and 29% for patients with p53 overexpression vs 60% for patients with no overexpression. On the other hand, the cumulative survival for nm23-H1 protein overexpression, altered Rb and p53 mutation did not differ significantly between negative and positive groups (p values 0.345, 0.287 and 0.539; respectively). On multivariate analysis, only increased EGFR expression (protein or RNA), the presence of metastasis and/or recurrence, a high tumor grade (GII &GIII) and a combination of aberrant markers (≥ 2) were significantly associated with reduced OS rates (p = 0.022&0.025, p = 0.000, p = 0.001, p = 0.001). On the other hand, p53 overexpression and advanced tumor stage (3b &4 vs 2&3a) showed a borderline significance (table 4)


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

Khaled HM, Bahnassy AA, Raafat AA, Zekri AR, Madboul MS, Mokhtar NM - BMC Cancer (2009)

Kaplan-Meier analysis for cases of BBC. Overall survival is significantly lower in patients with: (a) increased EGFR expression, (b) p53 overexpression, (c) combined (nm23 -ve and EGFR +ve), (d) combined (nm23 -ve and p53 +ve),
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2657793&req=5

Figure 3: Kaplan-Meier analysis for cases of BBC. Overall survival is significantly lower in patients with: (a) increased EGFR expression, (b) p53 overexpression, (c) combined (nm23 -ve and EGFR +ve), (d) combined (nm23 -ve and p53 +ve),
Mentions: On univariate analysis there was a statistically significant correlation between reduced OS rates and tumor type (SCC) (p = 0.043), high tumor grade (p = 0.008), local recurrence (p = 0.0001) and distant metastasis (p = 0.0001). A borderline significance was reported between advanced disease stage (3b+4 vs 2+3a) and reduced OS. Similarly reduced OS rates was significantly associated with loss of nm23-H1 RNA (p = 0.021), increased EGFR protein (Figure 3a) and EGFR RNA expression (p = 0.034 &p = 0.025) and p53 overexpression (p = 0.011) (Figure 3b). The cumulative survival for cases with normal nm23-H1 RNA expression was 64.8% whereas it was 35.5% for cases with reduced/lost nm23-H1 RNA. Likewise, the cumulative survival for EGFR positive patients was 41.0% compared to 69.0% for EGFR negative patients and 29% for patients with p53 overexpression vs 60% for patients with no overexpression. On the other hand, the cumulative survival for nm23-H1 protein overexpression, altered Rb and p53 mutation did not differ significantly between negative and positive groups (p values 0.345, 0.287 and 0.539; respectively). On multivariate analysis, only increased EGFR expression (protein or RNA), the presence of metastasis and/or recurrence, a high tumor grade (GII &GIII) and a combination of aberrant markers (≥ 2) were significantly associated with reduced OS rates (p = 0.022&0.025, p = 0.000, p = 0.001, p = 0.001). On the other hand, p53 overexpression and advanced tumor stage (3b &4 vs 2&3a) showed a borderline significance (table 4)

Bottom Line: 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 > or = 2 genes.In addition to the standard pathological prognostic factors, a combination of these markers (> or = 2) has synergistic effects in stratifying patients into variable risk groups.

View Article: PubMed Central - HTML - PubMed

Affiliation: Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt. khaled@internetegypt.com

ABSTRACT

Background: Clinical 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).

Methods: nm23-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.

Results: Overexpression 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 > or = 2 genes. However, multivariate analysis showed that only high EGFR overexpression, metastatic recurrence, high tumor grade and the combination of > or = 2 affected markers were independent prognostic factors.

Conclusion: nm23-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 (> or = 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.

Show MeSH
Related in: MedlinePlus