Abstract 3195: HMGA1 and HMGA2 over-expression in human lung carcinoma

Abstract

Abstract Background: Lung cancer is the leading cause of cancer death worldwide with an overall 5-year survival rate of only 15%. Therefore, research focusing on lung carcinogenesis is strongly needed. High mobility group A (HMGA) proteins play an important role in the regulation of transcription, differentiation, and neoplastic transformation. The HMGA gene family includes HMGA1, which encodes the HMGA1a and HMGA1b protein isoforms, and HMGA2, which encodes HMGA2. These chromatin-binding proteins function in transcriptional regulation and recent studies also suggest a role in cellular senescence. HMGA1 proteins also appear to participate in cell cycle regulation and malignant transformation, whereas HMGA2 has been implicated primarily in the pathogenesis of benign mesenchymal tumors. Aims: The aim of this study was to investigate on the potential role of HMGA 1 and 2 in lung carcinogenesis. Materials and methods: A tissue microarray (TMA) including normal and neoplastic non-small cell lung cancer (NSCLC; n=454) tissues was constructed and HMGA1 and 2 analyzed by immunohistochemistry. HMGA1 was detectable in a 454 patients and HMGA2 in 409 patients, respectively. Immunoreactivity was scored semi-quantitatively by evaluating the number of positive tumor cells over the total number of tumor cells. Scores were assigned using 5% intervals and ranged from 0% to 100%. Median protein expression levels were used as cut-off scores to define protein marker positivity and the findings were associated with clinical-pathological parameters. Results: HMGA1 and A2 are over-expressed in NSCLC tissues compared to normal lung (p<0,001), and more specifically, the HMGA2 expression is significant higher in non-adenocarcinomas than in adenocarcinomas (p<0,001. A significant relationship between HMGA2 over-expression and tumor grade (p<0,013), cN stage (p<0,037), cM stage (p<0,002), pT stage (p<0,003), pM stage (p<0,002), and recurrence (p<0,002). Additionally, HMGA1 over-expression showed a significant relationship with gender (p<0,003), tumor grade (p<0,028), pT stage (p<0,006) and recurrence (p<0,002). Conclusion: HMGA1 and A2 over-expression seems to play an important role in lung carcinogenesis and additional studies are needed to demonstrate a potential prognostic impact of HMGA1 and HMGA2 expression in NSCLC. 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 3195. doi:10.1158/1538-7445.AM2011-3195