Vol. 179, No. 4, Supplement, Monday, May 19, 2008 THE JOURNAL OF UROLOGY® 319

pathway, like FOXM1, H19 and IGF2, showed mRNA overexpression in tumor samples, as compared to normal bladder tissue.

CONCLUSIONS: These data suggest a potential involvement of the Hedgehog pathway in bladder carcinogenesis particularly

Shh overexpression and Ptc1 under Ptc1 under expression

pleads for its role as a potential tumor suppressor gene.Source of Funding: None

925SINGLE-NUCLEOTIDE POLYMORPHISM OF NINJURIN GENE IS ASSOCIATED WITH HIGHER RISK FOR HUMAN BLADDER CANCER PROGRESSIONLeopoldo A Ribeiro-Filho*, Pedro E M Guimaraes, Alvaro S Sarkis, Katia R Leite, Marcos F Dall’Oglio, Hiroaki Shiina, Mikio Igawa, Maria Cristina R Costa, Emmanuel Dias Neto, Rajvir Dahiya, Miguel Srougi. Sao Paulo, Brazil, Izumo, Japan, and San Francisco, CA.

INTRODUCTION AND OBJECTIVE: Ninjurin (nerve injury-induced protein) is an intercellular adhesion molecule and is reported to be regulated by p53. The ninjurin gene is mapped in 9q22, a region

polymorphism in the ninjurin gene (an A to C alteration) that promotes a change of an Aspartic acid to an Alanine at position 110 in the protein

of ninjurin gene can identify populations with higher risk for bladder cancer.

nucleotide polymorphism of Ninjurin gene in TCCB, or its progression, using a hospital based case-control study of 66 patients with TCCB (53 men and 13 women) 35 to 89 years old (mean age 65.6 ±10.9), and 108 normal male controls, 43 to 81 years old (mean age 60.4 ±8.5). Genomic DNA was extracted from blood samples. Genotypes were determined using polymerase chain reaction based restriction fragment length polymorphism technique. The C allele has a restriction site to the Hae

RESULTS: The frequency of AA, AC and CC genotypes were 58.3%, 37.9% and 3.7% in controls and 65.1%, 33.3% and 1.5% in patients respectively. The frequency of the C allele increases with

26.8% in grade III, n=29). Comparing grade I tumors and those with grade III we found more than two fold increse of C allele (p<0.05 OR

and invasive carcinoma (T2 to T4). C carrier patients also presented a shorter disease progression time (mean 19.3 months) when compared

of this study is that, if polymorphism of ninjurin gene can identify the subjects with higher risk for TCCB incidence and progression, then better strategies can be designed for the management of this disease.

risk assesment may be performed even before tumor presentation.Source of Funding: This project was supported by

NIH Research Grant R01 # D43 TW06215 funded by the Fogarty

926PIK3CA GENE MUTATIONAL ANALYSIS IN UROTHELIAL CARCINOMA OF URINARY BLADDERGeorge J Netto*, S Jadallah, D Hansel, J Cohen, K Murphy. Baltimore, MD.

INTRODUCTION AND OBJECTIVE: PIK3CA is a member of the Phosphatidylinositol 3-Kinase (PI3K) family. PI3K/akt/mTORpathway regulates cell proliferation, adhesion, survival and mobility. Genetic alterations in PIK3CA and other members of the pathway such as PTEN have been frequently found in a variety of epithelial neoplasms including colorectal and gastric carcinoma. PIK3CA gene mutations

marker for cancer detection and monitoring. Our study assesses PIK3CAmutation in urothelial carcinoma (UrCa).

METHODS: A total of 22 archival cystectomy specimens were

metastatic UrCa were mapped for tumor areas and microdissected for

were performed on each sample to span the target regions covering

with Sequencher 4.6 software.RESULTS: Sequencing failed in two cases. Sequencing of

exons 1, 9 and 20 was successful in 16 samples and was limited to two of the three exons in remaining four cases. None of the successfully sequenced PIK3CA genes showed any evidence of a mutation.

CONCLUSIONS: Mutation analysis of PIK3CA exons 1,9,and

We found no PIK3CA gene mutations in any of the 20 UrCa included in our pilot study. Although the possibility of mutations outside the hot

a low rate of PIK3CA mutations in UrCa. Additional studies including

role of PIK3CA oncogene activation in this setting.Source of Funding: NCI.

927EGFR v III MUTATION AND EGFR EXPRESSION IN UROTHELIAL CARCINOMA OF URINARY BLADDER: HIGH EGFR EXPRESSION IS NOT ASSOCIATED WITH EGFR v III MUTATIONGeorge J Netto*, S Jadallah, J Cohen, R Sharma, Antoun Toubaji, K Murphy. Baltimore, MD.

INTRODUCTION AND OBJECTIVE: Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase member of the ErbB family.

are low-molecular-weight ATP-competitive inhibitors that have been used with some success in the treatment of non small cell lung carcinoma (NSCLC) and other solid tumors. The presence of somatic EGFR variant III mutations has been shown to be predictive of response to TKI in NSCLC. Clinical trials of TKI agents in patients with advanced urothelial carcinoma (UrCa) are underway. The current pilot study assesses EGFRmutation status in UrCa.

were mapped for tumor areas and microdissected for DNA extraction

performed on each sample for EGFR exon 19 deletion and exon 21 L858Rmutation analyses using previously described primers and parametrs.

Scan 3.7 software (Applied Biosystems). For Exon 21 L858R mutation,

from all 22 cases were immunostained using monoclonal antibody for EGFR (Dako, CA). Intensity and distribution of EGFR expression were

or high ( any 2+ and or 3+ staining) EGFR expressors.

samples. None of the 20 informative UrCa samples revealed any evidence of EGFR Exon 19 deletion or Exon 21 L858R mutation. EGFRexpression was high in 11/22 (50%) tumors, low in 5 and absent in the remaining 6 tumors.

CONCLUSIONS: Mutation analysis of EGFR exons 19 and

tissue. We found no evidence of EGFR exon 19 deletion nor exon 21 L858R mutation in any of the 20 UrCa studied including 10 with high EGFR protein expression. Analysis of larger number of samples is needed. Although the possibility of other types of mutations exists, our results suggest a low rate of studied EGFR mutations in UrCa. Other

be investigated in this setting.Source of Funding: None