Abstract 5166: Identification of prostate stem cell antigen (PSCA) as a potential marker for lung cancer brain metastasis

Abstract

Abstract Background: Lung cancer is the leading cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) accounts for ∼80% of all lung cancers. Brain metastases (BMs) are estimated to occur in up to 40% of patients with NSCLC. DNA copy number changes are common in cancer and lead to altered expression and function of genes residing within the affected region of the genome. The aim of this study was to compare DNA copy number abnormalities between primary tumors (PT) and their corresponding BM in NSCLC to identify genomic regions associated with BM development by using array comparative genomic hybridization (aCGH). Material and Method: From surgically resected NSCLC formalin-fixed and paraffin-embedded (FFPE) tissues, we selected 28 paired PTs and BMs (24 adenocarcinomas, and 4 squamous cell carcinomas, SCCs), and 55 additional BMs (43 adenocarcinomas, 2 SCCs, and 10 NSCLCs) specimens for analysis. Using DNA extracted from FFPE tumor tissues we performed oligo-based aCGH in 10 paired PT and BM adenocarcinomas. Statistical aberration detection algorithms of data were conducted by aCGH with Nexus Copy Number software v5.0. Immunohistochemical (IHC) analysis of two proteins (PSCA and LY6K) coded by genes located in 8q24.3 region was performed in both PT and BM specimens. Results: In the aCGH analysis, multiple chromosomal regions with significant (P≤0.05) copy number gain and loss were detected. Whereas PT demonstrated 32 regions (harboring 933 genes) of copy number gain and 16 regions (108 genes) of copy number loss, BM showed 31 regions (1274 genes) with gains and 16 regions (90 genes) with losses. BM demonstrated significantly (P≤0.01) higher frequency of copy number gains in 3 chromosomal regions: 8q24.3 (BM 100% vs. PT 40%), 19q13.33 (BM 90% vs. PT 20%), and 20q13.12 (BM 60% vs. PT 0%). The 8q24.3 region with copy number gain in tumors harbors 7 genes, including Prostate Stem Cell Antigen (PSCA) and Lymphocyte Antigen 6 Complex Locus K (LY6K). Interestingly, in our IHC analysis, BMs (n=84; mean score 141.8) showed a significantly (P=0.008) higher score of expression of PSCA than the corresponding PTs (n=27; mean score 97.8). Similar significant differences were detected when we analyzed only adenocarcinomas samples. No significant differences in the level of IHC expression was detected comparing BMs (n=83; mean score 64) and PTs (n=27; mean score 68.5) for LY6K. Conclusions: By aCGH and subsequent protein expression analysis we have identified that PSCA may play an important role in the development of NSCLC brain metastasis. Similarly to prostate cancer, PSCA represents a novel potential marker for NSCLC metastasis and therapeutic target for advanced lung tumors. Supported by grant US DoD W81XWH-07-1-0306 and Jimmy L Hewlett Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5166. doi:10.1158/1538-7445.AM2011-5166