The influence of tumour cell DNA abnormalities on survival in colorectal cancer

Abstract

The cellular DNA content was measured from paraffin-embedded material in 134 colorectal cancers from patients in whom the outcome was known. Seventy-two (55 per cent) were found to contain cells with abnormal DNA (DNA aneuploid). The presence of such a population of cells was not related to pathological stage or histological grade. However, only 14 (19 per cent) patients with DNA aneuploid tumours survived 5 years compared with 27 (43 per cent) of patients with diploid tumours (chi 2 = 8.0, P = 0.005). Stepwise logistic analysis showed cellular DNA content to be an important prognostic factor in colorectal cancer, independent of pathological stage and histological grade.

Glucose starvation and acidosis: effect on experimental metastatic potential, DNA content and MTX resistance of murine tumour cells

“…Using three murine tumour cell lines (KHT, SCCVII and B16F1O) they found that transient hypoxia enhanced the metastatic potential and that this was associated with the generation of a subpopulation of overreplicated cells. Although this association is not specific, it is consistent with the finding that abnormal cellular DNA content can be associated with a reduced life expectancy in a number of human cancers (Cornelisse et al, 1987;Zimmermann et al, 1987;Armitage et al, 1985;Fordham et al, 1986;Cooke et al, 1990). It can be argued that overreplicated cells may give rise to cells with amplified genes that code for metastasis-relevant products (Ling et al, 1985) since it has been shown that cells resistant to MTX or doxorubicin due to amplification to the genes coding for DHFR or p-glycoprotein respectively were derived from overreplicated cells (Rice et al, 1987).…”

Flow cytometric DNA ploidy pattern in dysplastic mucosa, and in primary and metastatic carcinomas in patients with longstanding ulcerative colitis

“…Three of them also had aneuploid cell clones in tumour-distant flat mucosa, and these three were the only patients with metastatic disease (Table II). This is, however, interesting, since aneuploid carcinomas are associated with a worse prognosis than diploid ones (Wolley et al, 1982;Armitage et al, 1985;Rognum et al, 1987b;. The aneuploid cells in the mucosa from these three patients, all had DNA indices different from 1.7, and in two of the patients, the DNA index was the same as in the main carcinoma.…”

Ploidy as a prognostic indicator in end stage squamous cell carcinoma of the head and neck region treated with cisplatinum

“…Abnormal cellular DNA contents clearly worsen the prognosis in breast carcinoma (Cornlisse et al, 1987), bronchial carcinoma (Zimmerman et al, 1987), colorectal carcinoma (Armitage et al, 1985), prostatic carcinoma (Fordham et al, 1986) and squamous cell carcinoma at sites outside the head and neck, such as the lung (Blondal, 1981) and cervix (Jakobsen, 1984 No relationship was shown between ploidy and histological grade by Kaplan et al (1986), Johnson et al (1985 and Ensley et al (1989) but the frequency of DNA non-diploid tumours was found to correlate with a decrease in the histological grading by Holm (1982), Tytor et al (1987) and Feichter et al (1987, who also found that it was directly proportional to the percentage of cells in S-phase. We found no correlation between the degree of histological differentiation and DNA content.…”