DNA aneuploidy in colorectal adenomas

Quirke, Philip; Fozard, J. B. J.; Dixon, M. F.; Dyson, J. E.; Giles, G. R.; Bird, C. C.

doi:10.1038/bjc.1986.75

Cited by 106 publications

(48 citation statements)

References 29 publications

(30 reference statements)

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“…and histologic criteria (size, type, and degree of dysplasia), which are surely relevant for prognosis. As a n example, the incidence of adenomas smaller than 1 cm was in our case lower than in other studies (7,16). In general, one must say that much larger populations of patients would be required for correct comparative studies.…”

Section: Discussioncontrasting

confidence: 47%

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DNA flow cytometry of endoscopically examined colorectal adenomas and adenocarcinomas

Giaretti¹,

Sciallero

Bruno³

et al. 1988

Cytometry

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DNA ploidy of 64 colorectal adenomas and 49 adenocarcinomas, examined endoscopically, was studied by flow cytometry. We found DNA aneuploidy in none of the 105 normal mucosa samples (O%), in 20 adenomas (31%), and in 36 adenocarcinomas (74%). DNA ploidy of adenomas correlated with size ( P = 0.02) and degree of dysplasia ( P < 0.01) but not with histologic type. Adenomas had a 45% incidence of DNA aneuploid stem lines in the DNA index range of 0.80-1.20, compared with 8% in the case of adenocarcinomas. The distribution of the DNA index values of adenocarcinomas was approximately normal, with a mean value 1.63 f 0.28. The mean DNA index for the three cases of "carcinoma in adenoma" with invasion of the stalk of the adenoma was 1.52 f 0.18. These results, using DNA flow cytometry, provide evidence for the progression of colorectal adenoma to adenocarcinoma. The classification of adenomas according to DNA ploidy may be information of considerable practical value to the clinician in predicting risk of further adenomas andlor risk of cancer.

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Section: Discussioncontrasting

confidence: 47%

“…In the last study (241, about 20% of the polyps, associated with dysplasia, were DNA-aneuploid. The use of paraffin-embedded material appears to allow the detection of a lower incidence of DNA aneuploid cases, i.e., 6% (16) and 13% (6).…”

Section: Discussionmentioning

confidence: 99%

DNA flow cytometry of endoscopically examined colorectal adenomas and adenocarcinomas

Giaretti¹,

Sciallero

Bruno³

et al. 1988

Cytometry

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“…No increase in aneuploidy in adenomas associated with synchronous carcinoma has been described 196 . Owing to the inherent limitations of this technique, some tumours with subtle chromosomal aberrations or tumours with large chromosomal rearrangements that do not lead to changes in total DNA content, such as balanced translocations, will go undetected and be classi®ed as diploid.…”

Section: Cytometric Evidencementioning

confidence: 99%

“…The frequency of aneuploidy in adenomas is reported to be much lower 195,196 and correlates best with size (0 per cent in lesions of less than 1 cm, 16±52 per cent in lesions greater than 2 cm) and to a lesser degree with histological type (2 per cent in tubular adenomas, 11 per cent in villous adenomas) 196 . No increase in aneuploidy in adenomas associated with synchronous carcinoma has been described 196 .…”

Section: Cytometric Evidencementioning

confidence: 99%

The colorectal adenoma–carcinoma sequence

Leslie

Carey

Pratt

et al. 2002

British Journal of Surgery

597

448

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Background: It is widely accepted that the adenoma±carcinoma sequence represents the process by which most, if not all, colorectal cancers arise. The evidence supporting this hypothesis has increased rapidly in recent years and the purpose of this article is to review this evidence critically and highlight its clinical signi®cance.Methods: Medline searches were used to identify recent key articles relating to the adenoma±carcinoma sequence. Further pertinent articles were obtained by manual scanning of the reference lists of identi®ed papers.Results: The evidence supporting the adenoma±carcinoma sequence can be classi®ed as epidemiological, clinicopathological and genetic. The most recent and largest body of data relates to molecular genetic events and their cellular effects; however, many other approaches, such as cytogenetics, molecular cytogenetics and cytometry, have also yielded valuable information.Conclusion: Recent work continues to support the adenoma±carcinoma sequence, but there is a paucity of data on the interrelationship between different genetic mutations and on the relationship between molecular and other types of genetic abnormalities. The clinical utility of the observations described has yet to be fully realized and global genetic analysis of colorectal tumours may prove to be central in rational adenoma management. IntroductionColorectal cancer is the second leading cause of cancerrelated death in the Western world; in the UK there are currently around 30 000 new cases per annum and 17 000 related deaths 1 . In recent years our understanding of the cellular and molecular events underlying the development of colorectal cancer has improved immeasurably but, despite this and advances in surgery, radiotherapy and chemotherapy, the average 5-year survival rate remains around 40 per cent 1 . One of the most important fundamental concepts in colorectal cancer to emerge in recent years has been the adenoma±carcinoma sequence, a term that describes the stepwise progression from normal to dysplastic epithelium to carcinoma associated with the accumulation of multiple clonally selected genetic alterations. This concept not only provides an excellent model to study the genesis of invasive cancer, but also affords a means of preventing colorectal cancer by endoscopic removal of precursor lesions.The appropriate management of individuals with precursor adenomatous polyps (adenomas) is of the utmost importance. It is known that after removal of such polyps 30±35 per cent of patients will have further adenomas detected at 3±4 years 2±4 and this has led to a policy of endoscopic surveillance for all adenoma-bearers 5 . However, given that approximately 40 per cent of the Western population will develop adenomas 6±8 and only 3 per cent will go on to suffer from colorectal cancer, it is clear that only a small proportion of adenomas progress to malignancy. Unfortunately, there are no reliable criteria available that can predict adenoma progression or recurrence, and the important questions of which individuals...

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“…DNA flow cytometry Nuclear DNA measurements were performed on sections cut from paraffin embedded material from tumour and axillary nodes using a modification of the method of Hedley et al, (1983), as described in detail previously (Quirke et al, 1986). separated by gel electrophoresis using 0.7% agarose gels, transferred on to Hybond nylon filters and hybridised to 32P oligo-labelled probes (Feinberg & Vogelstein, 1983 (Tavassoli & Shall, 1988).…”

Section: Methodsmentioning

confidence: 99%

c-erbB-2/c-erbA co-amplification indicative of lymph node metastasis, and c-myc amplification of high tumour grade, in human breast carcinoma

Tavassoli

Quirke²,

Farzaneh³

et al. 1989

Br J Cancer

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Summary A panel of 73 samples, including 52 primary breast carcinomas, 10 normal breast tissues and 11 axillary lymph nodes, has been analysed for the presence of amplifications and gross structural alterations, in the oncogenes c-erbB-2, c-erbA, c-myc, N-myc, c-mos and c-Ha-ras. The tumours were also classified, graded and staged histopathologically and their DNA ploidy (42 samples) was determined by flow cytometry. Three breast cancer cell lines (MCF7, ZR-75-1 and T47D) were also included in the study. Amplification of c-erbB-2 was detected in 28% of the tumours, of which 91% had an increased steady-state level of c-erbB-2 mRNA. Amplification of c-erbA was found in 23% of tumours and was always associated with the amplification of c-erbB-2. Ten out of 12 (83%) tumours which had c-erbB-2 and c-erbA co-amplification had metastasised to axillary lymph nodes (P<0.006). However, the human thymidine kinase gene, which is present at the same chromosomal location as these two oncogenes (17q21-22), was amplified in only two tumours. Amplification of c-myc was detected in 21% of the tumours studied, of which 82% (P<0.005) were of histopathological grade 3 and none were of grade 1. Flow cytometry showed that 90% (P<0.01) of the analysed tumours with c-erbB-2 and c-erbA co-amplification, and 70% (P<0.1) of those with c-myc amplification were DNA aneuploid. This study demonstrates the potential value of c-myc amplification in the assessment of the tumour grade, rather than metastatic potential; and of the co-amplification of c-erbB-2 and c-erbA as a strong indicator of metastatic potential, rather than tumour grade.

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DNA aneuploidy in colorectal adenomas

Cited by 106 publications

References 29 publications

DNA flow cytometry of endoscopically examined colorectal adenomas and adenocarcinomas

DNA flow cytometry of endoscopically examined colorectal adenomas and adenocarcinomas

The colorectal adenoma–carcinoma sequence

c-erbB-2/c-erbA co-amplification indicative of lymph node metastasis, and c-myc amplification of high tumour grade, in human breast carcinoma

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