Numerical abnormalities of chromosomes 17 and 18 in sporadic colorectal cancer: Incidence and correlation with clinical and biological findings and the prognosis of the disease.
BACKGROUND
In recent years important information has accumulated on the genetic alterations present in colorectal tumors. However, thus far few studies have analyzed the impact of numerical abnormalities of chromosomes 17 and 18, which carry the p53 and DCC plus SHAD4/DPC4 genes involved in colorectal cancer, on the clinical and biological behaviors of the disease.


METHODS
With the use of interphase fluorescence in situ hybridization (FISH), we analyzed the incidence of numerical abnormalities of chromosomes 17 and 18 in a series of malignant colorectal tumors and explored its potential association with clinicobiological behavior and the prognosis of the disease. For this purpose, 94 consecutive patients newly diagnosed with colorectal cancer were analyzed. In all cases, FISH analyses of the number of copies and nuclei of chromosomes 17 and 18 were performed in interphase nuclei with the use of double stainings. For all patients, information on age, sex, tumor size, Dukes' stage, tumor localization, DNA ploidy status, and the proportion of S-phase tumor cells was recorded. Median follow-up was 38 months.


RESULTS
Numerical abnormalities of chromosomes 17 and 18 were present in most patients with colorectal cancer (57% and 52%, respectively). Gains of chromosome 17 and monosomy 18 were found in 51% and 29% of cases, respectively, and they were the most frequent individual abnormalities for each chromosome. The simultaneous analysis of the number of copies of both chromosomes in the same cell showed that, in most cases displaying numerical abnormalities for these chromosomes, two or more different tumor cell clones were present. From a clinical point of view, numerical abnormalities of chromosome 17, especially monosomy 17, were associated with a significantly higher incidence of rectal tumors (P = 0.001) and Dukes' stage D (P = 0.02) and a lower median of disease-free survival among patients who underwent curative surgery (P = 0.05), as compared with diploid cases. In addition, cases with an altered number of copies of chromosome 17 showed a higher incidence of DNA aneuploidy (P = 0.0001) and a greater proportion of S-phase cells (P = 0.001) by flow cytometry. In contrast, no clear association was found between the presence of numerical abnormalities of chromosome 18 and clinicobiological disease characteristics, except for a higher incidence of DNA aneuploidy by flow cytometry (P = 0.001) and a lower median of disease-free survival (P = 0.06). Multivariate analysis showed that numerical abnormalities of chromosome 17, but not of chromosome 18, are an independent prognostic factor for predicting disease-free survival in patients with colorectal cancer.


CONCLUSIONS
Numerical abnormalities of chromosomes 17 and 18 were relatively common findings in patients with colorectal cancer, with chromosome 17 being associated with a higher incidence of tumors localized to the rectum and a worse clinical outcome. Cytometry Part B (Clin. Cytometry) 51B:14-20, 2003.
Garcia
Jacinto
J
Servicio de Cirugia, Hospital Universitario and Departamento de Cirugia, Centro de Investigaciones del Cancer, Universidad de Salamanca, Salamanca, Spain.
Duran
Angel
A
Tabernero
Maria Dolores
MD
Garcia Plaza
Asunción
A
Flores Corral
Teresa
T
Najera
Maria Luisa
ML
Gomez-Alonso
Alberto
A
Orfao
Alberto
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D002887:Chromosomes, Human, Pair 18; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D016163:Genes, DCC / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis