Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The APC/MCC gene (Familial Adenomatous Polyposis) at 5q21 plays a role in colon cancer carcinogenesis. LOH at this locus has also been described in gastric cancer and preneoplastic lesions. The APC locus has been recently related to a cell surface adhesion molecule and its alteration may favour metastatic dissemination. LOH at 5q21 has been associated with poor prognosis in other tumors such as lung cancer. Thirty-six gastric cancers were evaluated for LOH at 5q21 with 2 polymorphic markers from microdissected paraffin-embedded material. All tumors were classified by stage, histologic type, degree of differentiation and survival rates. In 4 cases, intestinal metaplasia cells in the adjacent mucosae were also microdissected. Six cases of moderate-severe gastric dysplasia were also added to the study. LOH was determined in 84% of the informative cases of GC, affecting both early and advanced stages of disease. Genomic instability was assessed in 5 cases, 3 of them associated with LOH. The only case of gastric cancer that did not show LOH or instability at 5q21 was a stage II, poorly differentiated intestinal carcinoma without evidence of recurrence after a 36 month follow-up period (the mean survival rate in our series was 28.3% at 36 months). We also found LOH in 2/6 dysplastic lesions and 1/4 intestinal metaplasias. Our data show that LOH at 5q21 is frequent in gastric cancer and is also present in intestinal metaplasia and dysplastic lesions. LOH at this locus is not a prognostic factor in GC in our study, due to the high incidence of LOH that we found.
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PMID:LOH at the APC/MCC gene (5Q21) in gastric cancer and preneoplastic lesions. Prognostic implications. 918 90

Because of its propensity to spread along epithelial surfaces, colonic adenocarcinoma can mimic other neoplasms. For example, colonic adenocarcinoma can grow along the surface of the urinary bladder and can simulate primary bladder neoplasia, and metastatic colonic adenocarcinoma can grow along alveolar walls and can mimic primary lung neoplasia. Intraepithelial spread along bile ducts, however, is not a well-recognized behavior of hepatic metastases. Indeed, dysplastic change in the epithelium lining the biliary tract is sometimes used to discriminate primary biliary neoplasms from metastatic adenocarcinoma. We report on eight cases of colonic adenocarcinoma metastatic to the liver that demonstrated prominent spread throughout the biliary tree along intact basement membranes. Morphologically, this pattern closely resembled high-grade dysplasia (i.e., carcinoma in situ) of the extrahepatic and intrahepatic bile ducts. Clinically, two of the tumors were mistaken for primary biliary neoplasia because of the common radiologic finding of intrabiliary masses with distended bile ducts. A definite diagnosis of metastatic carcinoma was established by careful attention to the medical history, thorough evaluation of the morphologic features, and histologic comparison with the primary colon cancer. For patients with a history of colonic adenocarcinoma, consideration of a liver metastasis is appropriate even when certain histologic and radiographic features point to a neoplasm of biliary origin.
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PMID:Intrabiliary growth of metastatic colonic adenocarcinoma: a pattern of intrahepatic spread easily confused with primary neoplasia of the biliary tract. 929 79

Neoplastic progression in patients with chronic ulcerative colitis is characterized by the development of epithelial dysplasia, which is accompanied by genetic alterations. This study determined the time of onset of p53 and Ki-ras mutations as well as DNA aneuploidy during histological progression towards carcinoma. In all, 278 samples of 7 colectomy specimens were analyzed by flow cytometry, histology and single-strand conformation polymorphism analysis. Of the samples, 22% (61/278) were dysplastic and 43% (122/278) aneuploid, while 25% (71/278) showed p53 and 4% (11/278) Ki-ras mutations. The correlation between aneuploid status and p53 mutations varied among the patients. A strong correlation was noticed between histological progression from low-grade dysplasia to carcinoma and p53 mutations as well as DNA aneuploidy. Ki-ras mutations were found in 40% (2/5) of the carcinomatous samples. The correlation between p53 mutations and the histological status of the samples suggest the involvement of this genetic event in the development of colon cancer in patients with ulcerative colitis. In contrast to Ki-ras mutations, the appearance of p53 mutations is an early event. Therefore p53 analysis might be helpful in the classification of indefinite dysplasia and in the identification of patients at risk for cancer development. Further studies are necessary to detect the additional genetic alterations preceding the development of DNA aneuploidy.
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PMID:Comparative analysis of histology, DNA content, p53 and Ki-ras mutations in colectomy specimens with long-standing ulcerative colitis. 953 53

The prognostic value of quantitative pathological features in rectosigmoid adenomas was investigated, in search of more precise identifiers of adenoma-bearing patients at high risk of metachronous colorectal cancer. In a "nested case-control study" design, 21 cases with metachronous colon cancer during an average follow-up time of 16 years (range 3-30 years) after polypectomy and 67 controls were selected from a cohort of 1618 patients. The most advanced adenoma of each patient was analysed. Cases were matched with up to three controls simultaneously for size, grade of dysplasia, histological type, and number of adenomas, as well as for duration of follow-up. The patients did not undergo any post-polypectomy surveillance. Geometric characteristics of tumour nuclei, the arrangement of nuclei in the epithelium, and glandular changes were measured, and mitoses were counted. Several quantitative features measuring nuclear polymorphism and crowding showed significant prognostic value, while those measuring glandular changes and mitotic activity did not. A multivariate combination of the average distance between nuclei and the standard deviation of nuclear area discriminated an unfavourable group (n = 44) with 17 metachronous cancers from a favourable group (n = 44) with four metachronous cancers (P = 0*001, RR = 6*3). With the optimum cut-off, 28 patients without any metachronous cancer were discriminated from a group of 60 patients with 21 metachronous cancers. In conclusion, in the present study, quantitative pathological features assessed in rectosigmoid adenomas showed prognostic value additional to traditional measures. These features may therefore be useful in guiding post-polypectomy surveillance.
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PMID:Predicting the risk of metachronous colorectal cancer in patients with rectosigmoid adenoma using quantitative pathological features. A case-control study. 958 29

Some recent studies of the effects of chemopreventive agents have begun to use new rodent models to improve the analysis of stages of colonic preneoplasia, and how chemopreventive agents modify progressive abnormal cell development. In one of the models of inherited predisposition to colon cancer, mice carrying a truncated Apc allele with a nonsense mutation in exon 15 have been generated by gene targeting and embryonic stem cell technology (Apc1638 mice). These mice develop multiple gastrointestinal lesions, including adenomas and carcinomas, focal areas of high-grade dysplasia (FAD), and polypoid hyperplasias with FADS. The incidence of inherited colonic neoplasms has now been modulated by a chemopreventive regimen. Colonic lesions significantly increased in Apc1638 mice on a Western-style diet, which has higher fat content and lower calcium and vitamin D compared to the same mice on AIN-76A diet. In another rodent model, Min mice were treated with sulindac, which markedly reduced the incidence of intestinal tumors. A third new rodent model containing a targeted mutation in the gene Mcc (mutated in colorectal cancer) recently became available for chemoprevention studies. These mice develop multiple types of neoplasms including adenocarcinomas, focal areas of gastrointestinal dysplasia, papillomas of the forestomach, and tumors in other organs including lung, liver, and lymphoid tissue. Feeding a Western-style diet to the Mcc mutant mice also resulted in significantly increased gastrointestinal lesions. These nutrient modifications also have been given to normal mice, demonstrating without any chemical carcinogen that a Western-style diet induced colonic tumorigenesis. Western-style diets also have now induced modulation of cell proliferation in other organs including mammary gland, pancreas, and prostate. These findings help develop new preclinical rodent models to aid the analysis of genetic and environmental factors leading to neoplasia, as well as new methods for evaluating the chemopreventive efficacy of specific nutrients and pharmacological agents.
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PMID:New rodent models for studies of chemopreventive agents. 958 60

The transforming growth factor-beta (TGF-beta) type II receptor (RII) is a colon cancer suppressor gene that is inactivated by mutation in 90% of human colon cancers arising via the microsatellite instability (MSI) pathway of carcinogenesis. To determine the pathophysiological consequence of RII mutations, we have determined the timing of their onset among 22 MSI human colon adenomas of varying stages. No RII mutations were detected in any early MSI adenoma, including all those with simple tubular or villous histology. The earliest RII mutation detected was in a region of high-grade dysplasia but was absent from the surrounding simple adenoma. Six additional RII mutations were all found in highly progressed adenomas that contained regions of frankly invasive adenocarcinoma. These RII mutations were detected in both the advanced adenomas and their adjacent regions of carcinoma. RII mutation is a late event in MSI adenomas and correlates tightly with progression of these adenomas to cancer.
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PMID:Mutation of the type II transforming growth factor-beta receptor is coincident with the transformation of human colon adenomas to malignant carcinomas. 967 77

The cotton-top tamarin is a nonhuman primate noted for susceptibility to juvenile onset colitis and subsequent colon cancer. About 80% develop colitis in captive environments outside the tropics. The aim was to determine the prevalence of colitis and colorectal cancer in tamarins living wild in their tropical habitat. Endoscopic biopsy was used to compare severity of colitis, inflammatory/immune cell densities, mucosal dysplasia, and occurrence of cancer in wild tamarins in a tropical habitat with tamarins living captive in a temperate climate. Six colon biopsies from each of 69 captives showed severe colitis in 64.5% of biopsies and moderate colitis in 19.5%. Severe colitis was not found in 88 wild tamarins; 13% had moderate colitis. Densities of polymorphonuclear leukocytes, plasma cells, and mononuclear cells in the lamina propria were related directly to the severity of four grades of colitis (normal, mild, moderate, and severe). Histologic or gross signs of carcinoma were detected in 12 captives and low- or high-grade dysplasia in 15. Neither cancer nor dysplasia was found in any of the wild tamarins. The observations suggest that colitis and cancer in the tamarin model are linked to environmental factors.
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PMID:Colitis and colon cancer in cotton-top tamarins (Saguinus oedipus oedipus) living wild in their natural habitat. 969 Mar 78

We analyzed somatic mutation and loss of heterozygosity (LOH) in the serine/threonine kinase 11 (STK11)/Peutz-Jeghers syndrome gene in 49 colorectal tumors in three different stages of a dysplasia-carcinoma sequence. We detected LOH in 10 of 19 (52.6%) informative colorectal cancers at loci D19S886 and/or D19S883, but no LOH was observed in 25 informative adenomas. We detected a total of 9 somatic mutations [7 of 13 (53.8%) left-sided colon cancers and 2 of 7 (28.6%) left-sided adenomas with high-grade dysplasia], but no mutations were detected in right-sided colon tumors. Of the nine mutations, one was a frameshift mutation (the same mutation detected in Peutz-Jeghers syndrome family previously), and the other eight were missense mutations. This results indicate that STK11 is a tumor suppressor gene and that genetic changes of STK11 play an important role in left-sided colon cancer carcinogenesis.
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PMID:Frequent somatic mutations in serine/threonine kinase 11/Peutz-Jeghers syndrome gene in left-sided colon cancer. 973 85

Functional inactivation of the p16INK4a gene has been reported to be involved in the development of a variety of human malignancies. Recent evidence shows that transcriptional silencing as a consequence of hypermethylation of CpG islands is the predominant mechanism of p16INK4a gene inactivation in sporadic colon cancer. This study sought to identify the significance of p16INK4a methylation in the colonic epithelium of patients with long-standing ulcerative colitis. A total of 89 tissue samples was retrieved from three colectomy specimens. A methylation-specific PCR assay was applied. The methylation status was compared with histological findings and the flow cytometrically determined DNA index. Hypermethylation of the p16INK4a promoter region was detected in 12.7% of samples that were negative for dysplasia. However, 70.0% of samples with dysplasia and all of the samples with carcinomatous lesions revealed hypermethylation. Hypermethylation of the p16INK4a gene promoter was detected already in 40% of specimens with lesions indefinite for dysplasia and in 13.7% of samples with exclusively diploid cell populations. These results suggest that hypermethylation of the p16INK4a promoter region is a frequent and early occurring event during the process of neoplastic progression in ulcerative colitis.
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PMID:Hypermethylation of the p16INK4a promoter in colectomy specimens of patients with long-standing and extensive ulcerative colitis. 973 6

A patient with ulcerative colitis, extensive dysplasia, multifocal colon cancer, and an appendiceal cystadenoma is described. A 48-year-old man with a 26-year history of ulcerative colitis (UC) had extensive dysplasia involving nearly the entire colon and four dysplasia-associated mass lesions (DALMs). Four invasive adenocarcinomas were present. This case is the first documentation of a DALM (mucinous cystadenoma) arising in the appendix in the setting of UC. The genetic alterations present in the various lesions were analyzed. The molecular profiles of the neoplastic lesions differed. Mutations were found in p53 and ras genes, and one site showed microsatellite instability in a single genetic locus. These molecular abnormalities develop before invasive cancer develops, and may undergo clonal expansion to create large mucosal patches containing certain cells with genetic alterations. The diversity of the early changes suggests that the recurrent inflammation characteristic of long-standing UC randomly damages genes known to participate in colon carcinogenesis and that it affects multiple target genes. The findings also support a multiclonal origin of synchronous tumors because the molecular phenotypes of the preinvasive lesions differed at various sites.
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PMID:Multifocal neoplasia involving the colon and appendix in ulcerative colitis: pathological and molecular features. 983 86


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