Genetic changes in Slovenian patients with gastric adenocarcinoma evaluated in terms of microsatellite DNA.
OBJECTIVE
Adenocarcinoma of the stomach is a relatively frequent malignant disease in Slovenia. We investigated the frequency of microsatellite instability (MSI) and loss of heterozygosity (LOH) in gastric carcinomas from the Slovenian population to determine their prognostic significance.


METHODS
We evaluated MSI of mismatch repair associated loci and LOH on loci associated with following tumour suppressors: APC, nm23, Rb and p53. Results of the multiplex-PCR amplifications were correlated with clinicopathological factors for 73 patients.


RESULTS
LOH was found in 52% of informative samples (20.5% LOH-H; 31.5% LOH-L). We found correlation of MSI with low-frequency LOH (LOH-L) in 11% of cases and with high-frequency LOH (LOH-H) tumours in 4% of cases. LOH-H and high-frequency MSI (MSI-H) were not associated. LOH was found in APC 36%, p53 33%, Rb 24% and nm23 33% of informative samples, whereas MSI was found in 30% of samples (12% MSI-H; 18% MSI-L). LOH-H status was associated with ulceration (P=0.029). LOH-N status was associated with diagnosis at higher TNM status (0.074) and infiltrative growth (P=0.006). Interestingly, in 6% of samples we found MSI on LOH loci as well. MSI-H was associated with higher age at diagnosis (r=0.24; P=0.04), antral location (r=0.252; P=0.04), intestinal type (P=0.044), expansive growth (P=0.001), tubular type (0.014), better differentiation (P=0.01), less nodal involvement (0.006) and better survival (P=0.022). The poorest prognosis was found in patients with both low-frequency MSI (MSI-L) and low-frequency LOH (LOH-L) tumours.


CONCLUSIONS
The experimental design presented in the study may be of potential value for clinicians: at least five relevant markers for both MSI and LOH analysis may be needed to evaluate a gastric cancer (GC) patient's clinical status.
Gazvoda
Barbara
B
Medical Centre for Molecular Biology, Institute of Biochemistry, University of Ljubljana, Ljubljana, Slovenia.
Juvan
Robert
R
Zupanic-Pajnic
Irena
I
Repse
Stanislav
S
Ferlan-Marolt
Ksaverija
K
Balazic
Joze
J
Komel
Radovan
R
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction / Q000379:methods; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis
D004273:DNA, Neoplasm