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Multiple genetic alterations were investigated in colorectal cancer, including changes in DNA content, mutations in ras oncogenes, and deletions involving chromosomes 5, 17, and 18. A non-random association of deletions and mitotic abnormalities by site was seen, with both types of alterations occurring significantly more frequently in distal tumours. In contrast, the frequency of c-Ki-ras mutations did not differ between proximal and distal cancers. In addition, deletions were significantly associated with each other and with change in DNA content. The data provide strong support for the hypothesis that proximal and distal colon carcinoma might differ in the genetic mechanisms in their initiation and/or progression.

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That most cytotoxic agents act specifically against actively proliferating cells is well-recognized. In this study, we attempted to correlate pretreatment S-phase fractions (SPF) measured on DNA histograms with regression of the tumor mass after the administration of neoadjuvant chemotherapy. Tumor cells were obtained from 60 previously untreated, premenopausal patients with no metastases and with noninflammatory disease by fine needle sampling without aspiration. We could evaluate DNA ploidy in all patients and SPF in 50 or 83% of them. Tumor responsiveness was significantly related to SPF. The 12 patients who had SPF of 10% or more showed demonstrable regression; six had complete responses. None of the other parameters tested, i.e., DNA ploidy, histopathologic grade, or hormone receptor content, correlated with response. We believe this information may prove valuable for clinicians as they make their decisions regarding patient therapy.

Summary Allelic losses on the short arm of chromosome 17 occur frequently in colorectal cancers. Despite the existence of other common molecular events such as loss of the long arms of chromosomes 18 and 5, it has been demonstrated that the former has the greatest prognostic significance. Of the various genes mapping to the commonly deleted sequence, the best candidate as a 'target' seems to be the p53 antioncogene. We applied our An increasing body of evidence implicates the cellular antioncogene p53 in the development of human colorectal malignancy. In parallel to the discovery of the recurrent loss of the short arm of chromosome 17 (17p) by cytogenetic analysis (Muleris et al., 1985;, allelic losses were described, with probes specific for the short arm of chromosome 17, as well as for other chromosome segments (Fearon et al., 1987;Law et al., 1988; Delattre et al., 1989;Vogelstein et al., 1989;Fearon et al., 1990). The deletions on 17p were found to encompass a common region containing the p53 gene ) and mutations have been described in a number of cancer specimens The aim of the present study was to investigate the influence of the p53 content of cancer cells on the outcome of the disease. Two monoclonal antibodies (MAbs) recognising epitopes present on the wild-type protein (pAb 421: C-terminal and 1801: N-terminal) and the mutant-specific pAb 240 were used. Immunoreactivity was assayed on nuclear suspensions obtained by dissociation of surgical specimens of colorectal cancer and on the soluble fractions using a two point ELISA. Materials and methodsThe breast cancer cell line MDA-MB231 was cultured in a 1:1 mixture of DMEM and HAM F12 with 10% foetal calf serum (FCS) and 2% glutamine. A-431 cells (squamous carcinoma of the vulva) and HeLa cells (carcinoma of the cervix) were cultured in DMEM with 10% FCS. HL-60, myeloid leukaemia cells were cultured in RPMI 1640 with 20% FCS. In all cases exponentially growing cultures were harvested as previously described (Hammel et al., 1991) and stored in liquid nitrogen.A-431 and MDA-MB231 cells, which have been shown to contain homozygous p53 mutations Chen et al., 1990), were used as positive controls, HeLa cells, in which the p53 protein has been reported to be undetectable (Matlashewski et al., 1986), and HL60 cells that do not contain p53 mRNA consecutive to large deletions in the gene (Wolf & Rotter, 1985), were used as negative controls. Seventy-eight specimens of colorectal adenocarcinoma, operated between November 1985 and December 1989 and stored in our tumour bank were included in the study. All tissue fragments from the periphery of the tumours as well as macroscopically normal mucosa were obtained immediately after operation and stored at -80'C for short term conservation or in liquid nitrogen. These included 2 stage A, 29 stage