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[Use of virtual endoscopy with computerized tomography in the identification of colorectal neoplasms. Prospective study with symptomatic patients].

INTRODUCTION: Aim of this study was to evaluate the sensitivity of virtual colonoscopy (CT colonography) in the identification of colorectal cancer and to define the limitations and the advantages of this imaging modality, as well as indications to the examination. MATERIAL AND METHODS: We examined prospectively 62 symptomatic patients aged 36 to 82 years (28 women and 34 men). All patients underwent both conventional and virtual colonoscopy on the same day; the conventional examination allowed exploration of the entire colon. RESULTS: Conventional colonoscopy identified 89 lesions 3-50 mm in diameter, namely 84 benign and 5 malignant lesions. No lesions were identified in 12 patients. CT colonography identified 52 of the 89 lesions, with 57.1% diagnostic accuracy. There were 11 false positives (82.5% positive predictive value and 52.2% specificity) and 37 false negatives (24.5% negative predictive value and 58.4% sensitivity). Sensitivity was significantly higher (85.7%) for polyps > or = 1 cm. CONCLUSIONS: Virtual colonoscopy is an imaging modality with good diagnostic yield, well tolerated by patients and with great potentials for further development. We suggest that the examination be performed in symptomatic patients who cannot undergo total colonoscopy or refuse the other imaging modalities. Further studies are warranted in larger series of patients, possibly introducing it in screening programs.

Adult↗

Immunohistochemical demonstration of altered intracellular localization of the C-Myc oncogene product in human colorectal neoplasms.

The distribution of the c-myc oncogene product p62 was examined by immunohistochemistry using the monoclonal antibody Mycl-9E10 in a series of 50 colorectal resections for carcinoma. The specimens were specially handled to ensure rapid fixation in formalin, and a significant improvement was shown in the quality and localization of staining compared with routinely handled specimens. Non-neoplastic mucosa showed the presence of nuclear staining of epithelial cells in 93 per cent of the samples, whilst all carcinomas showed cytoplasmic staining and infrequent nuclear staining. Adenomas showed an intermediate pattern, with significantly more frequent cytoplasmic distribution than non-neoplastic mucosa, but less than carcinomas. The results show that whilst fixation conditions are important in the immunolocalization of the c-myc protein product, there may be a consistent difference between non-neoplastic mucosa and carcinoma in the manner of association of p62 with the nucleus.

Carcinoma↗

Value of immunohistochemical detection of DNA mismatch repair proteins in predicting germline mutation in hereditary colorectal neoplasms.

The utility of immunohistochemistry (IHC) as a screening method for the identification of persons with mutations in the DNA mismatch repair (MMR) genes in hereditary nonpolyposis colorectal cancer (HNPCC) remains to be defined. In this study, we analyzed the value of IHC versus that of microsatellite instability (MSI) testing in predicting mutation status of the MLH1, MSH2, and MSH6 genes in colorectal carcinomas and adenomas, and explored the frequency and significance of immunohistochemical staining variability. The study samples included 83 carcinomas and 29 adenomas derived from 110 patients who had strong family histories of colorectal cancer. Our results showed that IHC correctly predicted MSI status in 76% of the cases with a specificity of 100%. The overall sensitivity of IHC in predicting a germline mutation was 79% (30 of 38) with a specificity of 89% (48 of 54), whereas that of MSI testing was 97% (30 of 31) with a specificity of 83% (35 of 42). Six of 31 analyzable cases that had a disease-causing mutation and exhibited MSI showed normal IHC. The lower sensitivity of IHC was caused mainly by its low sensitivity in detecting MLH1 gene mutation (4 of 9). Coexisting adenomas and carcinomas observed in the same slide (n=12) showed a similar or identical staining pattern for all three proteins. No significant difference was detected in the sensitivity of IHC or MSI in detecting a germline mutation between isolated adenomas and carcinomas. In IHC-positive cases, heterogeneous staining was noted in 30% to 40% of the cases with the three different antibodies, and cytoplasmic staining in 5% to 13%. Weak IHC (defined as positive staining in <10% of the tumor with weak intensity) was noted in 14 tumors: 5 for the MLH1 antibody, 1 for MSH2, and 8 for MSH6. One of the 5 MLH1 cases exhibited MSI and had an MLH1 germline mutation. Five of the 8 MSH6 cases exhibited MSI and had MSH2 germline mutations. In conclusion, our study shows that 1) IHC identifies a significant portion of colorectal tumors derived from MMR gene germline mutation carriers and can be used as an adjunct measure in the identification of HNPCC families, but IHC cannot replace MSI testing; 2) adenomas have similar MMR protein expression patterns as carcinomas and may serve as an adequate sample for screening purposes in the identification of patients with MMR mutations; 3) not all IHC-positive cases show uniform positivity throughout the tumor; and 4) weak and focal staining of an MMR protein may be associated with MSI or gene mutation or both, suggesting the need to incorporate staining intensity in further IHC studies.

Adaptor Proteins, Signal Transducing↗

Urokinase type plasminogen activator receptor expression in colorectal neoplasms.

BACKGROUND: The urokinase type plasminogen activator receptor (uPAR) may play a critical role in cancer invasion and metastasis. AIMS: To study the involvement of uPAR in colorectal carcinogenesis. METHODS: The cellular expression and localisation of uPAR were investigated in colorectal adenomas and invasive carcinomas by in situ hybridisation, immunohistochemistry, and northern and western blot analyses. RESULTS: uPAR mRNA expression was found mainly in the cytoplasm of dysplastic epithelial cells of 30% of adenomas with mild (19%), moderate (21%), and severe (47%) dysplasia, and in that of carcinomatous cells of 85% of invasive carcinomas: Dukes' stages A (72%), B (93%), and C (91%). Some stromal cells in the adjacent neoplastic epithelium were faintly positive. Immunoreactivity for uPAR was detected in dysplastic epithelial cells of 14% of adenomas and in carcinomatous cells of 49% of invasive carcinomas. uPAR mRNA and protein concentrations were significantly higher in severe than in mild or moderate dysplasia (p<0.05); they were notably higher in Dukes' stage A than in severe dysplasia (p<0.05), and significantly higher in Dukes' stage B than in stage A (p<0.05), but those in stage B were not different from those in stage C or in metastatic colorectal carcinomas of the liver. CONCLUSIONS: Colorectal adenoma uPAR, expressed essentially in dysplastic epithelial cells, was upregulated with increasing severity of atypia, and increased notably during the critical transition from severe dysplasic adenoma to invasive carcinoma. These findings implicate uPAR expression in the invasive and metastatic processes of colorectal cancer.

Blotting, Northern↗

[The role of portography with computed tomography in the diagnosis of liver metastases from colorectal neoplasms].

This study was performed to confirm the high sensitivity of CT during arterial portography (CTAP) versus US and dynamic CT in the diagnosis of liver metastases from colorectal cancer. Ninety patients with 108 colorectal cancers underwent US, dynamic CT and CTAP to investigate the presence of liver metastases. US depicted 39 metastases in 26 patients, dynamic CT 46 metastases in 29 patients and CTAP 54 lesions in 34 patients. CTAP detected 8 metastases missed at dynamic CT; 4 of them were < 1 cm in diameter, 3 ranged 1-2 cm and one metastasis > 2 cm in diameter. After preoperative investigations only 7 patients were considered for hepatic resection. At surgery, palpation and intraoperative US of the liver detected two more metastases in the same patients. Our experience, in agreement with recent studies, confirms CTAP as the most sensitive preoperative method in detecting liver metastases and its superiority to be most apparent in lesions < 1 cm in diameter. Therefore, we consider CTAP an essential imaging technique for planning the correct treatment of liver metastases.

Adult↗

Expression of EGF, EGF-receptor, p53, v-erb B and ras p21 in colorectal neoplasms by immunostaining paraffin-embedded tissues.

Immunohistochemical studies were performed to clarify the significance of the expression or overexpression of epidermal growth factor (EGF), EGF-receptor (EGFR), p53, v-erb B, ras p21 in 23 cases each of tubular adenoma and adenocarcinoma. The expression of EGF, EGFR, p53, v-erb B, and ras p21 in paraffin-embedded tissues, from 46 patients with colorectal tumors (adenoma: 23 cases; 14 mild dysplasia, six moderate dysplasia, three severe dysplasia, adenocarcinoma: 23 cases; 17 well differentiated, two moderately differentiated, three poorly differentiated, one mucinous carcinoma was analyzed immunohistochemically using anti-EGF, EGFR, p53, v-erb B and ras p21 antibodies. The EGF and ras p21 tended to express more strongly in carcinoma cases than in the adenoma cases, and in severe and moderate dysplasia than in mild dysplasia (EGF: stained positive in five adenomas [21.74%] and 17 adenocarcinomas [73.91%]; ras p21: stained positive in six adenomas [26.09%] and 14 adenocarcinomas [60.87%]. The EGFR stained positive in two adenomas (8.70%) and two adenocarcinomas (8.70%). The p53 and v-erb B showed positive staining only in the carcinoma cases (p53: stained positive in four cases [17.39%]; v-erb B: stained positive in eight cases [34.78%]). This study suggests that these factors seem to have some role in the progression of colon neoplasms. It suggests that genetic alteration is not always equal to the overexpression of protein products, but that it reflects them well, and that the staining makes some contribution to differential diagnosis in colorectal neoplasms.

Adenocarcinoma↗

DNA hypermethylation in colorectal neoplasms and inflammatory bowel disease: a mini review.

DNA hypermethylation is one of major epigenetic changes. Hypermethylation of many genes has been reported to be related with carcinogenesis and tumor progression of colorectal cancer. Some genes including estrogen receptor is associated with ageing, and changes related with ageing may be accelerated in inflammatory bowel disease. Furthermore, fecal DNA methylation will be able to be used as a marker of colorectal cancer and inflammatory bowel disease. Evaluation of hypermethylation potentially contributes diagnosis of colorectal diseases.

Animals↗

[Clinical relevance of unusual metastases from colorectal neoplasms].

BACKGROUND: The aim of the study was to evaluate the clinical relevance of isolated metastases (MII) in unusual sites (different from liver and lung), synchronous and metachronous, in patients operated on for colorectal carcinoma (CCR). METHODS: The study was performed on 655 patients who underwent surgery for CCR during the period 1985-2000. Work out for distance metastases was performed (both during preoperative evaluation and follow-up) with physical examination and other few exams (CEA, chest X-ray, abdominal US scan). Other investigations were carried out if requested by clinical features. Metastases localized in sites different from liver and lungs were considered unusual. RESULTS: Metastases in unusual sites usually are observed in patients with terminal neoplastic disease. MII was found in only 7 (1.07%) patients, all submitted to resection of the primary tumor. Sites of unusual metastases were bones (3), CNS (2), adrenal gland and anus; such lesions were easily diagnosed by clinical features or by few examinations. Curative treatment was feasible in only three patients, and actually it did improve neither survival, nor quality of life. CONCLUSIONS: Extra-abdominal MII are rare, generally they cannot be treated; therefore particular tests for early diagnosis of such lesions appear useless. Potentially curative surgery for splenic and adrenal metastases is described in the literature; anyhow these lesions are usually shown by routine investigations.

Adult↗

["Field cancerization"--an additional phenomenon in development of colon tumors? K-ras codon 12 mutations in normal colonic mucosa of patients with colorectal neoplasms].

INTRODUCTION: The c-K-ras2-gene (K-ras) encodes the p21ras protein, which participates in the transduction of mitogenic signals from the cell surface to the nucleus. About 40-50% of colorectal cancers bear a point mutation of the K-ras codon 12 within exon I, leading to activation of the K-ras oncogene. METHODS: Using a polymerase chain reaction (PCR)-based two-step restriction fragment length polymorphism (2sRFLP)-technique, we assessed the frequency of point mutations in the first or second base of K-ras codon 12 in patients suffering from colorectal carcinoma, adenoma, and their normal colon mucosa, respectively. RESULTS: Similar to other investigators, we found mutations in 7 out of 17 (41%) colorectal carcinomas and 1 out of 4 (25%) adenomas. Using this very sensitive 2sRFLP technique (detection level = 0.2% of mutated cells), we were able to find K-ras codon 12 mutations in normal mucosa in 4 out of 18 (22.2%) patients with colorectal neoplasia. CONCLUSIONS: This result can be explained by the phenomenon of "field cancerization" or by a local micrometastasis of K-ras-positive tumor cells.

Adenocarcinoma↗