PMID- 20978325 OWN - NLM STAT- MEDLINE DCOM- 20110315 LR - 20211020 IS - 2210-7185 (Electronic) IS - 2210-7177 (Print) IS - 2210-7177 (Linking) VI - 33 IP - 3 DP - 2010 TI - Tumor necrosis factor-alpha is associated with positive lymph node status in patients with recurrence of colorectal cancer--indications for anti-TNF-alpha agents in cancer treatment. PG - 151-63 LID - 10.3233/ACP-CLO-2010-0539 [doi] AB - INTRODUCTION: The progressive growth of malignancies is accompanied by a decline in the immune response through mechanisms which are poorly understood. Apoptosis and induction of inflammation by tumor released cytokines as tumor escape mechanisms have been proposed to play an important role in colorectal carcinogenesis. METHODS: Expression of Tumor necrosis factor-alpha (TNF-alpha) was analyzed in colorectal cancer specimen and the cancer cell line HT-29 by immunohistochemistry and RT-PCR. TNF-alpha expression on protein and mRNA level were correlated with clinical characteristics and impact on survival. TNFR-1 was co-labelled with TNF-alpha and CD8+ cytotoxic T cells in immunofluorescence double staining experiments. RESULTS: 94% (n=98/104) of the patients with CRC expressed TNF-alpha. High TNF-alpha expression was significantly associated with positive lymph node stage and recurrence of the tumor. Multivariate analysis revealed high TNF-alpha expression as an independent prognostic factor. Immunohistochemistry was correlated with RT-PCR results (tau=0.794). Immunofluorescence double staining experiments revealed increased TNFR-1 expression by CD8+ cells. CONCLUSIONS: TNF-alpha expression by tumor cells may be an efficient immunological escape mechanism by inflammation-enhanced metastases and probably by induction of apoptosis in tumor-infiltrating CD8+ immune cells resulting in a down regulation of the tumoral immune response. Our data support the role of tumor-derived TNF-alpha expression as an important promoter of tumoral immune escape mechanisms and malignant progression, and suggest that analysis on either protein (immunohistochemistry) or RNA level (RT-PCR) can be used effectively in this respect. Targeting TNF-alpha may be a promising option, especially in cases with high TNF-alpha expression and positive lymph node metastases. FAU - Grimm, M AU - Grimm M AD - Department of General, Visceral, Vascular and Pediatric Surgery, University of Wurzburg Hospital, Wurzburg, Germany. Grimm_M@chirurgie.uni-wuerzburg.de FAU - Lazariotou, M AU - Lazariotou M FAU - Kircher, S AU - Kircher S FAU - Hofelmayr, A AU - Hofelmayr A FAU - Germer, C T AU - Germer CT FAU - von Rahden, B H A AU - von Rahden BH FAU - Waaga-Gasser, A M AU - Waaga-Gasser AM FAU - Gasser, M AU - Gasser M LA - eng PT - Journal Article PL - United States TA - Anal Cell Pathol (Amst) JT - Analytical cellular pathology (Amsterdam) JID - 101541993 RN - 0 (Tumor Necrosis Factor-alpha) SB - IM EIN - Cell Oncol (Dordr). 2011 Aug;34(4):407-9 MH - Colorectal Neoplasms/genetics/*metabolism MH - HT29 Cells MH - Humans MH - Immunohistochemistry MH - Lymphatic Metastasis/*physiopathology MH - Neoplasm Recurrence, Local/metabolism/*physiopathology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/genetics/*metabolism PMC - PMC4605536 EDAT- 2010/10/28 06:00 MHDA- 2011/03/16 06:00 PMCR- 2010/10/26 CRDT- 2010/10/28 06:00 PHST- 2010/10/28 06:00 [entrez] PHST- 2010/10/28 06:00 [pubmed] PHST- 2011/03/16 06:00 [medline] PHST- 2010/10/26 00:00 [pmc-release] AID - W2774871284106P3 [pii] AID - 891869 [pii] AID - 10.3233/ACP-CLO-2010-0539 [doi] PST - ppublish SO - Anal Cell Pathol (Amst). 2010;33(3):151-63. doi: 10.3233/ACP-CLO-2010-0539.