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PURPOSE To test whether p34cdc2 overexpression, CD44s downregulation, and HER-2/neu amplification correlate with disease recurrence after radical prostatectomy, and to evaluate a possible biologic association between p34cdc2 and HER-2/neu expression. MATERIALS AND METHODS Immunohistochemical (IHC) detection of both p34cdc2 cyclin-dependent kinase (CDK) and CD44s expression and fluorescence in situ hybridization (FISH)-based analysis of HER-2/neu gene status were performed on formalin-fixed, paraffin-embedded sections of 106 prostatic adenocarcinomas (PACs). Findings were correlated with Gleason grade, pathologic stage, DNA ploidy, and postsurgical biochemical disease recurrence. RESULTS CDK overexpression correlated with tumor grade (P = .001), DNA ploidy (P = .001), pathologic stage (P = .04), and disease recurrence (P = .01). CD44s downregulation correlated with grade (P = .03), ploidy (P = .01), and recurrence (P = .02). HER-2/neu amplification correlated with grade (P = .001), ploidy (P = .001), and recurrence (P = .01). On multivariate analysis, CDK overexpression independently predicted recurrence (P = .001) after prostatectomy. CDK expression correlated with HER-2/neu status with 32 of 65 (49%) tumors that overexpressed CDK and showed concomitant HER-2/neu amplification (P = .04). CONCLUSION This study showed that p34cdc2, CD44s, and HER-2/neu are variably expressed or amplified in prostatic carcinoma and that such alteration may affect tumor behavior. In addition, CDK overexpression and HER-2/neu amplification may be biologically related.

10564 Background: With the increasing availability of genomically targeted therapies, the comprehensive description of patient tumor genomes can be an effective diagnostic approach that informs opt...

22076 Background: WWP1, a HECT type E3 ubiquitin ligase, is frequently amplified and overexpressed in breast cancer and may associated with positive ER status. IGF-1R is a tyrosine kinase growth fa...

10571 Background: Mammalian target of rapamycin (mTOR) regulates several cell functions critical to tumorigenesis including proliferation, growth, mobility and survival. mTOR expression and dysregulation have been reported carcinomas of breast, head & neck, liver and kidney, but have not yet been studied in non small cell lung cancers (NSCLC), colorectal adenocarcinomas (CRC), nor brain tumors including gemistocytic astrocytomas (GA) and glioblastomas (GBM). Methods: Formalin-fixed paraffin-embedded tissue sections from 121 NSCLC [45 squamous cell carcinomas (SCC), 45 pure adenocarcinomas (AC), and 31 bronchioloalveolar carcinomas (BAC) including both pure BAC and adenocarcinomas with BAC features], 108 CRC, 8 GA and 24 GBM were immunostained by an automated method (Ventana Medical Systems, Tucson, AZ) using monoclonal rabbit anti-human p-mTOR antibody (Cell Signaling, Danvers, MA). Immunohistochemical assessment included intensity and percentage of positive cells in both benign and carcinomatous elements. Results were correlated with morphologic and prognostic variables in NSCLC and CRC and GBM. Results: Elevated p-mTOR expression was noted in 33% SCCs, 64% ACs, and 65% BAC, 78% CRC, 75% GA and 96% GBM. For NSCLC, increased expression of p-mTOR correlated with histologic subtype (p=0.004). Within SCC greater than 3 cm in size, only 20% had an increase in p-mTOR, while 53% of SCC ≤ 3 cm showed an increase in p-mTOR expression (p=0.03). 100% high grade vs. 43% low grade (p=0.05) and 100% advanced stage (p=0.037) vs. 54% low stage BAC showed an increase in p-mTOR. Consistently, 100% BACs with positive lymph node status vs. 54% node negative BACs showed an increased level of p-mTOR (p=0.037). For CRC, p-mTOR over-expression correlated with high tumor grade (80% Grade 3 vs 50% Grade 1 p=0.042). Majority of GA (6/8) and nearly all GBM (23/24) were positive for p-mTOR (p=0.135). Conclusions: Activated mTOR protein, defined by phosphorylation of mTOR at Serine-2448 (p-mTOR), is increased in NSCLC, CRC and both GA and GBM. These findings suggest a potential role for mTOR dysregulation in lung, colon and brain tumorigenesis and support the currently ongoing clinical trials investigating the therapeutic relevance of rapamycin analogs in the treatment of these tumors. No significant financial relationships to disclose.

7517 Background: Using a radioactive in situ hybridization method on primary melanoma (PM), loss of the melastatin (MLSN-1) mRNA expression has been found to have independent prognostic significance. In this study, we examined whether a new non-radioactive chromogenic ISH (CISH) method to evaluate melastatin expression would similarly predict PM outcome. Methods: Melastatin mRNA was evaluated by CISH on formalin fixed paraffin embedded tissues from 109 PM patients with localized disease (AJCC stages I and II). PMs were classified as having complete or partial down regulation of MLSN compared to internal control intraepidermal melanocytes. MLSN status was compared with standard prognostic factors over a mean clinical follow-up of 58 months with a range of 2 to 225 months. Results: On univariate analysis, partial or complete loss of MLSN expression, found in 32% and 27% of PM respectively, correlated with disease free survival (DFS) (p