Surgical margin status and prognosis of gastrointestinal stromal tumor.

BACKGROUND: Surgery is the best treatment for primary GIST and may be curative, but resection extension/completeness impact on the prognosis remains controversial. The authors aim was to evaluate the clinicopathological (CP) parameters and surgical margins status influence on GIST patients' outcome. MATERIALS AND METHODS: The study evaluated 113 consecutive patients with sporadic GIST; the influence of CP parameters on recurrence-free survival (RFS) and disease-specific survival (DSS) was determined by univariate analysis (UA) and multivariate analysis (MA). RESULTS: Of 104 cases, macroscopically complete resection was achieved in 96: R0 surgical margin status in 78 and R1 in 18. Recurrence rates (12.5%) were significantly lower in R0 (9.0%) than in R1 (27.8%). Tumor > 10 cm, mitotic count > 5/50 high power field (HPF), and high-risk GIST predicted poor RFS and DSS (UA). Disease-specific survival was significantly shorter after macroscopic incomplete (R2) resection, for mixed cellular morphology, and in tumors with necrosis (UA). High-risk GIST (p = 0.016) and R2 resection (p = 0.013) predicted poor DSS of patients (MA). CONCLUSIONS: High risk and positive macroscopic surgical margin status are parameters associated with poor disease-specific survival in GIST patients.

Who takes the lead in the development of ulcerative colitis-associated colorectal cancers: mutator, suppressor, or methylator pathway?

Although several genetic alterations have been identified in patients with ulcerative colitis (UC), it remains unclear whether these changes indicate an increased risk for malignancy. This paper analyzes the involvement of suppressor, mutator, and methylator pathways in malignant transformation associated with UC. A total of 60 colonic samples (47 affected non-neoplastic mucosa, 7 dysplasia, and 6 carcinoma) from 51 UC patients were analyzed for 22 microsatellite markers. p53 gene exons 5-8 were analyzed by single-strand conformational polymorphism, and APC gene by denaturing gradient gel electrophoresis (exons 1-14) and protein truncation test (exon 15). Methylation studies for MLH1 and CSPG2 genes were also performed. Microsatellite instability was absent in all samples whereas allelic imbalance (AI) and loss of heterozygosity (LOH) were detected mainly in samples with neoplastic transformation (P<0.0001). AI and/or LOH at loci located on chromosomes 5, 9, and 18 were significantly more frequent in neoplastic samples (P<0.01), as were TP53 gene mutations (P<0.007). A single mutation was detected for APC gene in a cancer sample. MLH1 gene methylation was absent in all analyzed samples, whereas CSPG2 gene methylation was detected in a single non-neoplastic sample. Our results suggest that the suppressor pathway plays the main role in UC associated tumorigenic progression. LOH at specific loci located on chromosomes 5, 9, and 18 appears to be specifically associated with malignancy risk.