Gene expressions of VEGF and Survivin as molecular markers of lymph node involvement in patients with locally advanced rectal cancer

Abstract

9526 Background: Patients diagnosed with locally advanced rectal cancer usually receive surgical resection and adjuvant radio-chemotherapy for their disease. Lymph node involvement is an important clinical prognostic factor affecting type of surgery, recurrence, and survival. Few studies have explored molecular markers associated with lymph node involvement. Methods: Tissue was obtained from 73 patients with locally advanced rectal cancer (UICC stage II and III) who were treated with adjuvant radio-chemotherapy. We assessed mRNA levels of genes involved in angiogenesis (VEGF, COX-2), apoptosis (Survivin), tumor growth and epidermal growth factor (EGFR), DNA repair (ERCC1, RAD51), and the 5-FU pathway (TS, DPD) from paraffin-embedded samples using laser-capture-microdissection methods. In tumor and adjacent normal tissue, univariate and multivariate (controlling for T stage) logistic regression models were used to examine the association between the expression level of each gene and lymph node involvement. Results: There were 25 women and 48 men with a median age of 52 (range 25–79) years. Thirty-five patients had no involvement of regional lymph nodes (pN0), 38 had lymph node metastases (pN+). Twenty-four of the 35 pN0 patients and 27 of the 38 pN+ patients were stage T3. The higher gene expression level of VEGF and Survivin in tumor tissue were statistically significantly associated with the higher likelihood of lymph node involvement compared with lower expression level when adjusting for T-stage (OR=3.16 and 2.24 for VEGF and Survivin, respectively, p <.05). The patients with higher expression level of DPD in tumor tissue or EGFR in adjacent normal tissue were at higher risk of lymph node involvement compared with those with the lower expression level (p <.10). Conclusions: Gene expressions of VEGF, SURVIVIN, DPD, and EGFR may be associated with lymph node involvement in patients with resected rectal cancer. Further studies of those gene expression levels and lymph node involvement are warranted to better characterize the associations. No significant financial relationships to disclose.