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


CONCLUSIONS
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.
Khaled
Hussein M
HM
Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt. khaled@internetegypt.com
Bahnassy
Abeer A
AA
Raafat
Amira A
AA
Zekri
Abdel-Rahman N
AR
Madboul
Maha S
MS
Mokhtar
Nadia M
NM
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000096:biosynthesis*; D012552:Schistosomiasis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology
D014408:Biomarkers, Tumor; D054778:NM23 Nucleoside Diphosphate Kinases; D012334:RNA, Neoplasm; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; C517938:NME1 protein, human