Microsatellite instability in patients with multiple primary cancers of the gastrointestinal tract.
BACKGROUND
Little is known about the genetic alterations in multiple primary cancers of the gastrointestinal tract. Microsatellite instability (MSI) is frequently observed in hereditary non-polyposis colorectal cancer (HNPCC), and multiple primary cancers is a feature of this syndrome.


OBJECTIVE
To identify MSI incidence, target gene mutation, and mismatch repair (MMR) protein status in patients with multiple primary cancers of the gastrointestinal tract.


METHODS
Fifty seven cancers from 22 Japanese patients with multiple primary cancers of the stomach, duodenum, colon, and rectum.


METHODS
MSI was examined at 5-7 microsatellite loci. Mutation analysis for TGFbetaRII, IGFIIR, and BAX was performed in cancers with MSI. MMR protein status was examined by immunohistochemical analysis using a monoclonal antibody against hMSH2 and hMLH1.


RESULTS
MSI was observed in 16 of 22 patients (73%) and in 29 of 57 lesions (51%). High frequency MSI (MSI-H) was found often in patients with multiple cancers in the same organ (p = 0.042), especially in multiple gastric cancer patients (p = 0.038). In contrast, patients with multiple cancers in different organs had a tendency to show low frequency MSI (MSI-L) or microsatellite stable (MSS) phenotype. Both target gene mutation and decreased expression of MMR protein were found only in seven lesions of three patients with MSI at more than four microsatellite loci.


CONCLUSIONS
These results suggest that genetic instability may play an important role in the development of multiple gastrointestinal cancers but there may be different genetic alterations between multiple gastrointestinal cancers of the same and different organs.
Yamashita
K
K
First Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan.
Arimura
Y
Y
Kurokawa
S
S
Itoh
F
F
Endo
T
T
Hirata
K
K
Imamura
A
A
Kondo
M
M
Sato
T
T
Imai
K
K
D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch / Q000235:genetics; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D017527:Receptor, IGF Type 2 / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017527:Receptor, IGF Type 2; D018125:Receptors, Transforming Growth Factor beta; D051028:bcl-2-Associated X Protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II