Apoptosis inducing factor is decreased in metastatic colon cancer in ex-vivo models of colon carcinogenesis by tissue microarray

Abstract

14539 Background: In vitro studies suggest that apoptosis inducing factor (AIF) expression is decreased in metastatic cells relative to those derived from primary tumors. This study was undertaken to determine AIF expression patterns in patients with stage I/II vs. stage III/IV colorectal cancers. Methods: Colon cancer specimens were prospectively collected (11/05–6/06) from 12 patients from 3 different sites: tumor, adjacent to tumor, and tissue 2 cm from the tumor. Paraffin-embedded specimens were examined by tissue microarray with AIF-specific antibodies. Total AIF expression as well as cytoplasmic and nuclear expression was assessed by an investigator blinded to the tissue site and patient stage. Staining was assessed as: 1=absent, 2=mild, 3=moderate, 4=high and 5=very high. The clinical characteristics and tumor stage of all patients were analyzed. Results: All patients were male. Eight patients had non-metastatic disease at the time of laparotomy, four had metastasis to: lymph nodes (n=3) and liver (n=1). Stage I/II patients (n=8) were of similar age compared to stage III/IV patients (n=4) [61.3±4.2 vs. 54.4±6.0 y.o.; p=0.6] had similar tumor size (3.81±0.7 vs. 4.08±1.4 cm; p=0.4). There was no difference in the level of expression of AIF in normal tissue collected 2-cm away from the tumor site in stage I/II vs. stage III/IV colon cancers in the cytoplasm (3.81±0.17 vs. 3.30±0.38; p=0.4), nucleus (3.19±0.43 vs. 2.49±0.46; p=0.8) or overall (4.06±0.27 vs. 3.37±0.8). A significant decrease in AIF expression was observed in stage III/IV tumors compared to stage I/II tumors in tissue collected adjacent to the tumor in the cytoplasm (3.12±0.22 vs. 4.46±0.25; p=0.03), the nucleus (2.10±0.44 vs. 3.63±0.32; p=0.03) and overall (3.12±0.22 vs. 4.46±0.25; p=0.03). There was a trend towards a decrease in AIF expression between stage III/IV vs. I/II tumors in tissue collected directly from the tumor in the cytoplasm (2.55±0.24 vs. 3.56±0.26; p=0.12), the nucleus (1.39±0.25 vs. 2.73±0.63; p=0.14) and overall (2.79±0.38 vs. 3.90±0.37; p=0.22). Conclusion: AIF expression is decreased in metastatic colon cancer. The main differences occur in the normal mucosa adjacent to the tumor. No significant financial relationships to disclose.