Chromosome instability evaluated by fluorescence in situ hybridization in hereditary non-polyposis colorectal cancer.
Numerical aberrations of chromosome 17 and nuclear DNA content were compared in patients with hereditary non-polyposis colorectal cancer (HNPCC) and those with sporadic colorectal cancer (SCRC). During a period of 22 years, 30 cases (3.2%) from 28 families satisfied the Japanese clinical criteria of HNPCC. Using freshly frozen tissue samples, we investigated chromosomal aberration with fluorescence in situ hybridization with alpha satellite DNA probe for chromosome 17. Flow cytometric quantification of nuclear DNA content showed DNA aneuploidy in 9 of 15 patients (60.0%) with HNPCC and in 160 of 234 patients (68.4%) with SCRC, there was no significant difference between HNPCC and SCRC. The mean proportion of nuclei with aneusomy 17 (numerical chromosome aberration index: NCAI) in 14 patients with HNPCC was significantly higher than that in 42 patients with SCRC (46.8 +/- 5.0% vs 39.0 +/- 10.3%, P < 0.01). NCAI increased in proportion with the progression of the disease in SCRC (26.1% in stage I, 33.3% in stage II, 38.8% in stage IIIa, 42.7% in stage IIIb, and 46.2% in stage IV, P < 0.01), whereas NCAI in HNPCC was high in all stages (43.5%-49.2%). The proportion of patients with multiple numerical aberration of chromosome 17 was significantly higher in HNPCC (9/14) than among SCRC (11/42). Our data suggest that chromosome 17 is present in an unstable condition in HNPCC.
First Department of Surgery, Nagasaki University School of Medicine, Sakamoto, Japan.
T
T
Sawai
O
O
Sasano
T
T
Tsuji
A
A
Nanashima
H
H
Yamaguchi
T
T
Yasutake
T
T
Nakagoe
H
H
Ayabe
Y
Y
Tagawa
D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D044466:Asian People / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D015342:DNA Probes; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007564:Japan; D008297:Male; D008875:Middle Aged; D013048:Specimen Handling
D015342:DNA Probes