title: Immune cells in primary and metastatic gastrointestinal stromal tumors (GIST).
abstract: We have previously described immune cells in untreated primary gastrointestinal stromal tumors (GIST). Here we compare immune cells in metastatic and primary GIST, and describe their chemoattractants. For this purpose, tissue microarrays from 196 patients, 188 primary and 51 metastasized GIST were constructed for paraffin staining. Quantitative analysis was performed for cells of macrophage lineage (Ki-M1P, CD68), T-cells (CD3, CD56) and B-cells (CD20). Chemokine gene-expression was evaluated by real-time RT-PCR. Immuno-localisation was verified by immunofluorescence. Ki-M1P+ cells were the predominant immune cells in both primary and metastatic GIST (2 8.8% ± 7.1, vs. 26.7% ± 6.3). CD68+ macrophages were significantly fewer, with no significant difference between primary GIST (3.6% ± 2.1) and metastases (4.6% ± 1.5). CD3+ T-cells were the most dominant lymphocytes with a significant increase in metastases (7.3% ± 2.3 vs. 2.2% ± 1.8 in primary GIST, P < 0.01). The percentage of CD56+ NK-cells was 1.1% ± 0.9 in the primary, and 2.4 ± 0.7 (P < 0.05) in the metastases. The number of CD20+ B-cells was generally low with 0.6% ± 0.7 in the primary and 1.8% ± 0.3 (P < 0.05) in the metastases. Analysis of the metastases showed significantly more Ki-M1P+ cells in peritoneal metastases (31.8% ± 7.4 vs. 18.2% ± 3.7, P < 0.01), whilst CD3+ T-cells were more common in liver metastases (11.7% ± 1.8 vs. 4.4% ± 2.6, P < 0.01). The highest transcript expression was seen for monocyte chemotactic protein 1 (MCP1/CCL2), macrophage inflammatory protein 1α (MIP-1α/CCL3) and the pro-angiogenic growth-related oncoprotein 1 (Gro-α/CXCL-1). Whilst the ligands were predominantly expressed in tumor cells, their receptors were mostly present in immune cells. This locally specific microenvironment might influence neoplastic progression of GIST at the different metastatic sites.
authors.affiliation: Clinic of Gastroenterology and Endocrinology, Georg-August University Göttingen, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Cameron
authors.affiliation: Clinic of Gastroenterology and Endocrinology, Georg-August University Göttingen, Germany.
authors.forename: Marieke
authors.initials: M
authors.lastname: Gieselmann
authors.affiliation: Clinic of Gastroenterology and Endocrinology, Georg-August University Göttingen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Blaschke
authors.affiliation: Clinic of Gastroenterology and Endocrinology, Georg-August University Göttingen, Germany.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Ramadori
authors.affiliation: Institute of Pathology, Georg-August University Göttingen, Germany ; Current address: Pius Hospital Oldenburg, Germany.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Füzesi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005455:Fluorescent Antibody Technique; D046152:Gastrointestinal Stromal Tumors / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment / Q000276:immunology*
keywords: Gastrointestinal stromal tumor (GIST); immune cells; liver metastasis; microenvironment; peritoneal metastasis