Clinical value of loss of heterozygosity in serum microsatellite DNA of patients with gastrointestinal stromal tumors.

GOALS: To study the role of loss of heterozygosity (LOH) in serum microsatellite DNA of patients with gastrointestinal stromal tumors (GIST). BACKGROUND: In GIST, tumor markers from peripheral blood are missing. STUDY: Seventy-eight patients (59 GIST, 13 leiomyomas, 2 leiomyosarcomas, and 4 schwannomas) underwent resection at our institute between 1985 and 2006. Thirty-three preoperative sera (26 GIST and 7 non-GIST) and 62 postoperative sera (47 GIST and 15 non-GIST) were available and tested for alterations in 12 representative microsatellite loci on chromosomes 22, 17, 13, 9, and 3, using fluorescence-based automated capillary electrophoresis by ABI Prism. Survival was calculated with Kaplan-Meier plots. RESULTS: Seventeen out of 26 GIST patients had a positive preoperative serum LOH score (> or =2 LOH, sensitivity 65.4%), and 6 out of 7 non-GIST patients had a negative score (< or =1 LOH, specificity 85.7%, P=0.030, Fisher exact test). Serum LOH in GIST were strongly correlated with Fletcher risk groups (P=0.016, chi test). All metastasized GIST (7/7) showed > or =2 LOH preoperatively. Postoperative sensitivity and specificity of LOH analysis for prediction of relapse in 47 GIST was 75.0% and 64.1%, respectively. After a median observation time of 51.3 months (95% confidence interval, 39.4-61.4), LOH in serum significantly predicted overall survival (P=0.007, log-rank test). CONCLUSIONS: LOH serum analysis in GIST may play a role as a noninvasive, differential diagnostic, prognostic, and monitoring marker in the clinical routine.

Short tandem repeat polymorphism in exon 4 of esophageal cancer-related gene 2 detected in genomic DNA is a prognostic marker for esophageal cancer.

BACKGROUND: Short tandem repeat (STR) polymorphisms in exon 4 of the esophageal cancer-related gene 2 (ECRG2) are a risk marker for esophageal carcinoma. The aim of the present study was to correlate these STRs with clinical outcome. METHODS: Genomic DNA of 86 patients who underwent complete surgical resection was analyzed for STRs TCA3/TCA3, TCA3/TCA4, and TCA4/TCA4 in exon 4 of ECRG2 by polymerase chain reaction and DNA sequencing. RESULTS: ECRG2 STR TCA3/TCA3 and TCA3/TCA4 were found in 40 (47%) patients, respectively, and TCA4/TCA4 in 6 (7%) cases. TCA3/TCA3 genotype was significantly associated with reduced survival (P < .05, log-rank test). TCA3/TCA3 STR was the strongest prognostic factor determined by multivariate Cox regression analysis. CONCLUSIONS: Genetically fixed STR polymorphism TCA3/TCA3 in exon 4 of ECRG2 is associated with poor clinical outcome in surgically treated esophageal cancer patients and might be a potential prognostic marker. The usefulness of these genetic markers to predict responsiveness toward neoadjuvant treatment of esophageal cancer patients would be of high clinical interest and should be examined in future studies.

Microsatellite analysis in serum DNA as a diagnostic tool for distinction of patients with unknown pancreatic masses.

The clinical distinction between cancer and chronic pancreatitis is difficult in patients with pancreatic masses. To test whether detection of aberrant serum DNA could assist in this important differential diagnosis, we tested a panel of 12 microsatellitemarkers from chromosomes 17p, 17q, 13q, 9p, 5q, and 2p in the blood of 35 pancreatic cancer patients, 22 patients with chronic pancreatitis, and 20 healthy individuals. An average of 2.8 loss of heterozygosity (LOH) was found in 32 of 35 cancer patients of whom 30 (86%) had 2 or more LOH. LOH was also found in 7 of 22 pancreatitis patients but all these patients had only 1 LOH. No LOH was detected in healthy donors of comparable age. These data suggest that LOH analysis may be a substantial help for diagnosing pancreatic masses. An extension of the panel, perhaps in combination with a better selection of markers may further improve this assay.

Similar patterns of loss of heterozygosity in serum of adenocarcinoma of the distal oesophagus and the cardia in early diagnosis.

BACKGROUND: Loss of heterozygosity (LOH) may be a valuable tool for detection of malignant proceedings. The aim of our study was to investigate LOH in the serum of patients with adenocarcinoma of the distal oesophagus and the cardia for diagnostic and prognostic utility. PATIENTS AND METHODS: Matched tumour and serum samples from 46 surgically treated patients with oesophageal adenocarcinoma and cardia carcinoma divided in two groups were analysed. Twelve markers were examined with a PCR-based microsatellite analysis. RESULTS: A similar high frequency of LOH (range from 77% to 96%) was detected in the tumour and serum of both groups, whereas no LOH was detected in 20 healthy individuals. However, no significant correlation between LOH incidence and clinicopathological characteristics and survival was found. CONCLUSION: The results indicate that DNA alterations in tumours of the oesophagus and cardia are uniform. The high frequency of LOH in tumour patients underlines the utility of this molecular approach as a diagnostic tool.

Squamous cell carcinoma of the esophagus can be detected by microsatellite analysis in tumor and serum.

PURPOSE: Esophageal squamous cell cancer can be treated effectively by potentially curative surgery if diagnosed at an early stage. Our aim was to develop a novel molecular approach as a noninvasive test for squamous cell cancer detection and as an indicator for the prognosis of the patients. EXPERIMENTAL DESIGN: Matched normal, tumor, and serum samples were obtained from 28 patients with squamous cell carcinoma (SCC) of the esophagus. DNA was extracted, and the samples were subjected to microsatellite analysis using 12 markers. Serum and normal DNA from 10 healthy individuals served as controls. RESULTS: Twenty-six of the 28 patients (92.9%) with SCC were found to have one or more microsatellite DNA alterations in their primary tumor. Twenty-seven of the 28 patients (96.4%) had at least one alteration in the serum by microsatellite analysis. Mean age was 61.5 years. Microsatellite alterations were not identified in the serum DNA of samples from normal control subjects. Median follow-up was 13 months. Survival and recurrence were not significantly correlated with either loss of heterozygosity in the tumor or in the serum. CONCLUSIONS: Microsatellite DNA analysis of tumor and serum specimen is a potentially valuable tool for detection and for the evaluation of the prognosis of SCC of the esophagus. The follow-up in our study is still too short to draw final conclusions on the correlation of disease-specific survival and disease recurrence with microsatellite alterations. The evidence of circulating tumor DNA in almost all of our patients underlines a systemic component of the disease that is not surgically amenable.