Decreased T cell infiltration and lymphocyte/dendritic cell/monocyte gene expression as well as increased Cyp3A5 mRNA predicts early recurrence of non-small cell lung cancer (NSCLC) following surgical resection

Abstract

7141 BackgroundRecent phase III data (T. Le Chevalier et al., Proc Am Soc Clin Oncol, 2003) indicate a potential benefit of adjuvant chemotherapy in NSCLC, following surgical resection. Thus, we examined whether cDNA microarray analysis could be used to identify markers that correlate with early recurrence of NSCLC in patients treated with surgery alone. Methods An observational protocol to assay NSCLC tissue banked at resection from patients with stage Ia-IIIb tumors was implemented, using a longitudinal database. The patients were stratified into two groups: Group A (n=15) exhibited no recurrence at two years following surgery and Group B (n=11) exhibited recurrence, documented by tissue diagnosis. Group A was 73% stage I, 20% stage II and 7% stage III. Group B was 36% stage I, 9% stage II and 55% stage III. All evaluable patients were included in the analysis. RNA was isolated from whole tumor tissue and individual tumors were compared using U133 Affymetrix chips. Results A set of 35 T and B cell, dendritic cell and monocyte mRNA species was significantly increased in Group A compared to Group B (F test P<0.0043). Group A tumors exhibited intraepithelial tumor infiltrating T cells (TIL) in 80% (12/15) of cases, by CD2 IHC, compared to 27% (3/11) of Group B (P=0.022). Cyp3A5 mRNA was increased 18.7-fold in Group B (P=0.0001), Notch3 1.7-fold (P=0.002) and collagen 18A1 2.2-fold (P=0.005). Conclusions A set of 35 gene expression markers from lymphocytes/dendritic cells/monocytes negatively associated with early relapse of NSCLC has been identified. Intraepithelial T cell tumor infiltration is confirmed to be negatively associated with relapse. These results suggest that infiltration by specific lymphocyte, dendritic, and monocyte cell types inhibits NSCLC recurrence. Increased Cyp3A5, Notch3 and collagen 18A1 mRNA also correlates with recurrence. These markers may help determine which NSCLC patients may benefit from adjuvant chemotherapy. This work was supported by NIH Grant P20-GM66402–02 and the Thoracic Oncology Program at Indiana University. No significant financial relationships to disclose.