Simultaneous monitoring of P53 protein and dna content of colorectal adenocarcinomas by flow cytometry

Remvikos, Yorghos; Laurent‐Puig, Pierre; Salmon, Rémy; Frelat, G.; Dutrillaux, Bernard; Thomas, Gilles

doi:10.1002/ijc.2910450313

Cited by 75 publications

(42 citation statements)

References 22 publications

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“…Baker et al (1989) has demonstrated mutation of the p53 gene in two tumours associated with increased mRNA production. Remvikos et al (1990) found a significant association between elevated p53 and the presence of DNA aneuploidy but not Dukes' stage. They did not however investigate cell proliferation or prognosis.…”

Section: Discussionmentioning

confidence: 80%

p53 in colorectal cancer: clinicopathological correlation and prognostic significance

Scott

Sagar²,

Stewart³

et al. 1991

Br J Cancer

214

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Summary p53 protein was detected by immunohistochemistry in 42% of 52 colorectal adenocarcinomas. Positive tumours were significantly more frequent in the distal colon, and demonstrated a higher rate of cell proliferation. No correlation was found with tumour grade, Dukes' stage, presence of DNA aneuploidy or patient survival. The role of p53 in colorectal carcinogenesis is discussed with particular reference to differences between proximal and distal large bowel cancers. p53 is a 53kD nuclear protein, highly conserved in vertebrates, which is believed to regulate entry into and progression through the normal cell cycle (Mercer et al., 1984). Like c-myc it is induced during transition from Go to G, phase (Milner & Milner, 1981;Reich & Levine, 1984), and is present at low levels in most normal fetal and adult tissues (Rogel et al., 1985). Studies of p53 expression in cultured cells suggest that increased levels are associated either with an abnormal mutated protein (Finlay et al., 1988), or stablisation of the protein in a complex with viral antigens, e.g. SV40 large T antigen (Lane & Crawford, 1979). Point mutations occurring in a highly conserved region of the gene are known to activate p53 in the primary rat embryo fibroblast transfection assay for dominant oncogenes , whereas the wild type protein has a tumour suppressor action . The presence of increased levels of protein may therefore provide a marker for mutated p53.Elevated p53 expression has been described in a number of human tumours including carcinoma of the breast (Crawford et al., 1984;Cattoretti et al., 1988;Thompson et al., 1990), colorectum (Crawford et al., 1984), and lung (Iggo et al., 1990). Colorectal cancer is characterised by frequent deletion of chromosome 17p close to the p53 locus (Vogelstein et al., 1988), and elevated protein levels have been found by radioimmunoassay in 44% of tumours (Crawford et al., 1984). These studies suggest that in some tumours hemizygous deletion of one p53 allele is accompanied by mutation and overexpression of the other. Recently van den Berg et al. (1989) described the immunohistochemical detection of p53 in 55% of 29 colorectal cancers. However no information was given regarding the relationship of p53 expression to clinico-pathological variables several of which are believed to correlate with the biological aggressiveness and stage of progression of a tumour. The aim of the present study was to assess these relationships in a larger series and investigate the value of the immunocytochemical detection of p53 as a prognostic indicator. Materials and methodsFresh tumour tissue was obtained from 52 adenocarcinomas of the large bowel from 52 patients. A single 4 p frozen section was cut from each tumour, air dried overnight, and fixed for 15 min in acetone at 4'C.In five cases tissue was available from up to five different areas of the same tumour. These were included in the main series in order to assess the effect of intra-tumour heterogeneity on the detection of p53.Sections were incubated with Pab421, ...

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Section: Discussionmentioning

confidence: 80%

p53 in colorectal cancer: clinicopathological correlation and prognostic significance

Scott

Sagar²,

Stewart³

et al. 1991

Br J Cancer

214

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“…Statistical analysis of follow-up data of 47 patients with gastric carcinoma (20 with p53 positive and 27 with p53 negative tumours) and of 80 patients operated on for colorectal cancer (36 with p53 positive and 44 with p53 negative tumours), revealed that p53 overexpression in both carcinomas is significantly associated with early relapse and death (P<0.001). Thus,18 (Crawford et al, 1984;Remvikos et al, 1990;Rodrigues et al, 1990;Scott et al, 1991;Campo et al, 1991 (Fielding & Priestman, 1986;Preece et al, 1986). The prognosis is worse for cancers which originate in the upper third of stomach or in the rectum.…”

Section: Resultsmentioning

confidence: 99%

“…It also has been demonstrated that colorectal carcinomas of the fungating type metastasised less frequently than ulcerative tumours (Fielding & Priestman, 1986 There is no published data on the prognostic significance of p53 protein in gastric cancer and little is known about its role in determining prognosis in colorectal carcinoma. Remvikos et al (1990), investigated 41 colorectal tumours and found a significant association between elevated p53 and the presence of DNA aneuploidy, a factor connected with poor prognosis but not with Dukes stage. They suggested that evaluating p53 expression may prove useful in determining different biological subgroups of colorectal cancer.…”

Section: Resultsmentioning

confidence: 99%

Prognostic significance of p53 overexpression in gastric and colorectal carcinoma

Starzyńska

Bromley²,

Ghosh³

et al. 1992

Br J Cancer

209

106

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The p53 gene mapped on chromosome 17p is an important negative regulator of normal cell growth and division (Finlay et al., 1989;Chen et al., 1990;Diller et al., 1990;Isaacs et at., 1991). Alteration or inactivation of p53 by mutation can allow a cell to escape from normal into uncontrolled growth leading to cancer development. p53 mutations are a very common genetic change in a variety of human tumours Takahashi et al., 1989;Nigro et al., 1989;Bartek et al., 1990a;Marks et al., 1991;Tamura et al., 1991). The majority of the mutations alter the conformation of the nuclear protein product, encoded by the p53 gene (Gannon et al., 1990;Bartek et al., 1990b; Rodrigues et al., 1990). In normal cells and tissues the p53 protein has a very short half-life (Oren et al., 1981) and attains such a low level that it is not detectable histologically (Gannon et al., 1990). The mutant forms have an extended half-life (Finlay et al., 1988) and being overexpressed are readily detected by immunohistochemistry. Elevated p53 levels have been described in different human neoplasms (Crawford et al., 1984;Cattoretti et al., 1988;Bartek et al., 1990a;Iggo et al., 1990;Davidoff et al., 1991a;Marks et al., 1991

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“…Mutations in this gene constitute some of the most frequently occurring genetic changes at human malignancies and are thought to be late development in the adenoma -carcinoma sequence in CRC (Fearon and Vogelstein, 1990). Mutations in this gene increase the protein half-life and are often associated with protein overexpression in the nucleus (Remvikos et al, 1990). Mutations most commonly occur in the highly conserved region (exons 5 -8), which encodes the DNAbinding domain (Zhang et al, 1997).…”

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confidence: 99%

Genetic and epigenetic changes in primary metastatic and nonmetastatic colorectal cancer

et al. 2006

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Colorectal cancer (CRC) develops as multistep process, which involves genetic and epigenetic alterations. K-Ras, p53 and B-Raf mutations and RASSF1A, E-Cadherin and p16INK4A promoter methylation were investigated in 202 CRCs with and without lymph node and/or liver metastasis, to assess whether gene abnormalities are related to a metastogenic phenotype. K-Ras, B-Raf and p53 mutations were detected in 27, 3 and 32% of the cases, with K-Ras mutations significantly associated with metastatic tumour (P ¼ 0.019). RASSF1A, E-Cadherin and p16INK4A methylation was documented in 20, 44 and 33% of the cases with p16INK4A significantly associated with metastatic tumours (P ¼ 0.001). Overall, out of 202 tumours, 34 (17%) did not show any molecular change, 125 (62%) had one or two and 43 (21%) three or more. Primary but yet metastatic CRCs were prevalent in the latter group (P ¼ 0.023) where the most frequent combination was one genetic (K-Ras in particular) and two epigenetic alterations. In conclusion, this analysis provided to detect some molecular differences between primary metastatic and nonmetastatic CRCs, with K-Ras and p16INK4A statistically altered in metastatic tumours; particular gene combinations, such as coincidental K-Ras mutation with two methylated genes are associated to a metastogenic phenotype.

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Simultaneous monitoring of P53 protein and dna content of colorectal adenocarcinomas by flow cytometry

Cited by 75 publications

References 22 publications

p53 in colorectal cancer: clinicopathological correlation and prognostic significance

p53 in colorectal cancer: clinicopathological correlation and prognostic significance

Prognostic significance of p53 overexpression in gastric and colorectal carcinoma

Genetic and epigenetic changes in primary metastatic and nonmetastatic colorectal cancer

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