Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serrated adenoma has been proposed to be a distinct entity among colorectal neoplasms. Progression to frank carcinoma has been suggested in individual cases, but the prevalence of carcinomas originating from serrated adenomas and their clinico-pathological characteristics are not known. In the present study, a large series of colorectal cancers was analysed for the occurrence of serrated adenoma in association with carcinoma and clinico-pathological features were compared in cases with and without serrated adenoma. Specimens from 466 colorectal carcinoma patients undergoing operations between 1986 and 1996 were re-evaluated for the presence of juxtaposed serrated adenoma and carcinoma. Clinico-pathological features such as location, Dukes' stage, histological grade, mucinous differentiation, and prognosis were evaluated. Twenty-seven carcinomas (5.8%) were found in association with an adjacent serrated adenoma. Eight of the patients were male and 19 were female. All of these adenocarcinomas showed a serrated appearance resembling that of serrated adenomas. Nine (33%) cases were mucinous and a mucinous component was present in 11 (41%) additional cases. The majority of the tumours were located either in the caecum (14 cases; 51%) or in the rectum (9 cases; 33%). DNA microsatellite instability was more common in carcinomas associated with serrated adenoma (37.5%) than in other carcinomas (11.0%). It is concluded that carcinoma associated with serrated adenoma is a distinct type of colorectal neoplasm, accounting for 5.8% of all colorectal carcinoma cases in this study. Predilection for the caecum and the rectum may reflect their aetiological factors. Female preponderance is contrary to that reported for hyperplastic polyps and serrated adenomas.
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PMID:Colorectal carcinoma associated with serrated adenoma--prevalence, histological features, and prognosis. 1124 5

Proteolytic enzymes, such as type IV collagenases (MMP-2 gelatinase A, 72-kD type IV collagenase and MMP-9 gelatinase B, 92-kD type IV collagenase) play an important role in tumor invasion and metastasis. In the present study the levels of MMP-2 antigenic concentration and immunohistochemical staining were compared in paired colorectal tumor (n = 64) and background colon tissue of the same patients with clinical and pathological staging. The antigenic concentrations were found to be statistically significantly higher in cancer tissue (mean 11.29 ng/mg protein) than in corresponding normal mucosa (10.23 ng/mg protein) (p = 0.008). There was also a positive correlation between MMP-2 antigenic concentration and clinicopathologic parameters such as grade (p < 0.001) and Dukes' stage (p = 0.001), but not with lymph node involvement. Immunohistological localization of MMP-2 was observed in tumor as well as in stromal cells. Staining intensity increased from adenoma to adenocarcinoma. The degree of staining was associated with grade (p < 0.001), Dukes' stage (p < 0.001) and lymph node involvement (p < 0.001).
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PMID:Expression of gelatinase-A (MMP-2) in human colon cancer and normal colon mucosa. 1178 32

Despite the advances in the medical care of colorectal carcinoma patients, the prognosis has improved only marginally over recent decades. Thus, additional prognostic indicators would be of great clinical value to select patients for adjuvant therapy. In the present study, the antigen levels of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1, and their immunohistochemical staining were compared in paired colorectal tumor (n = 64) and background colon tissue of the same patients with clinical and pathological staging. The antigen levels, measured with an ELISA method, were found to be significantly higher in cancer tissue (mean 1.92 ng/mg protein for uPA and 7.08 for PAI-1) than in corresponding normal mucosa (0.29 ng/mg protein for uPA and 1.11 ng/mg protein for PAI-1). There was a positive correlation between uPA and PAI-1 antigen levels and clinicopathological parameters such as grade (p < 0.001 and p = 0.01, respectively), while for Dukes' stage, only PAI-1 correlated positively (p = 0.018). Nodal status correlated positively with uPA but not with PAI-1 antigen levels. Immunohistochemical localization of both antigens was observed mainly in cancer cells and much less in stromal cells. Staining intensity increased from adenoma to adenocarcinoma. The degree of staining was associated with grade, Dukes' stage and nodal status for uPA (p < 0.001, p = 0.002, p < 0.001, respectively) and only with grade for PAI-1 (p = 0.007).
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PMID:Significance of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 (PAI-1) expression in human colorectal carcinomas. 1221 97

Activation of the RAS/RAF/extracellular signal-regulated kinase-mitogen-activated protein kinase/extracellular signal-regulated kinase/mitogen-activated protein kinase pathway by RAS mutations is commonly found in human cancers. Recently, we reported that mutation of BRAF provides an alternative route for activation of this signaling pathway and can be found in melanomas, colorectal cancers, and ovarian tumors. Here we perform an extensive characterization of BRAF mutations in a large series of colorectal tumors in various stages of neoplastic transformation. BRAF mutations were found in 11 of 215 (5.1%) colorectal adenocarcinomas, 3 of 108 (2.8%) sporadic adenomas, 1 of 63 (1.6%) adenomas from familial adenomatous polyposis (FAP) patients, and 1 of 3 (33%) hyperplastic polyps. KRAS mutations were detected in 34% of carcinomas, 31% of sporadic adenomas, 9% of FAP adenomas, and no hyperplastic polyps. Eight of 16 BRAF mutations were V599E, the previously described hotspot, and none of these was associated with a KRAS mutation in the same lesion. The remaining eight mutations involve other conserved amino acids in the kinase domain, and 62.5% have a KRAS mutation in the same tumor. Our data suggest that BRAF mutations are, to some extent, biologically similar to RAS mutations in colorectal cancer because both occur at approximately the same stage of the adenoma-carcinoma sequence, both are associated with villous morphology, and both are less common in adenomas from FAP cases. By contrast, colorectal adenocarcinomas with BRAF mutations are associated with early Dukes' tumor stages (P = 0.006) and no such relationship was observed for KRAS mutations. The presence in some colorectal neoplasms of mutations in both BRAF and KRAS suggests that modulation of the RAS-RAF-extracellular signal-regulated kinase-mitogen-activated protein kinase/extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway may occur by mutation of multiple components.
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PMID:Similarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia. 1243 34

Angiogenic cytokines in the plasma and serum of cancer patients may serve as 'surrogate' markers of tumour neoangiogenesis. Serum VEGF correlates with disease stage in colorectal cancer (CRC), but the role of bFGF in CRC is uncertain. This study aimed to assess plasma bFGF levels in CRC patients before treatment, during chemoradiotherapy and at one-year follow-up. Plasma samples were taken from 124 CRC patients, 26 polyp patients and 55 controls, and bFGF levels were measured by ELISA. 19 patients underwent pre-operative chemoradiotherapy. One-year follow-up samples were available from 48 disease-free patients and 18 patients with progressive disease. There were no detectable differences between plasma bFGF levels in polyp, Dukes' A or B patients (4.55, 5.77, 4.25 pg/ml, respectively), but there was a significant increase in metastatic CRC patients [Dukes' C and D (7.42 and 6.6 pg/ml; P = 0.004 and 0.048, respectively)], relative to median control levels of 4.14 pg/ml. At follow-up, there was a significant fall in plasma bFGF levels in disease-free patients (pre-op 6.09 and follow-up 3.45 pg/ml, P = 0.0004), but a non-significant rise in 18 patients with progressive disease (pre-treatment 5.90 and follow-up 9.99 pg/ml, P = 0.33). Pre-treatment plasma bFGF in patients receiving chemo-radiotherapy was similar in those with responsive and non-responsive tumours. There were no detectable changes in plasma bFGF through the adenoma-carcinoma sequence or patient groups with non-metastatic cancers. Elevated plasma bFGF was, however, associated with metastatic spread. The significant fall in bFGF in disease-free patients following therapy suggests that bFGF may be useful in clinical practice.
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PMID:Plasma basic fibroblast growth factor levels in colorectal cancer: a clinically useful assay? 1255 80

Tumor angiogenesis, a crucial step in tumor growth and progression, is regulated by an increasing number of angiogenic factors. One of those is platelet-derived endothelial cell growth factor, recently shown to bethymidine phosphorylase (TP), which reversibly catalyzes the phosphorylation of thymidine to deoxyribose-1-phosphate and thymine. TP overexpression in tumors has been reported, but the differential expression of this enzyme in the colorectal adenoma-carcinoma sequence has not been examined in detail. In this study we analyzed 16 hyperplastic polyps, 37 solitary tubular and tubulovillous adenomas (ranging from 1 to 7.5cm, median 3.2cm), and 47 cases of colorectal carcinomas arising on the basis of pre-existing adenomas (25 cases were Dukes' A, 10 Dukes' B and 12 Dukes' C). Non-neoplastic colonic mucosa was also examined separately from all the above carcinoma cases. All samples were stained for TP and assessed for vascularity. Normal mucosa, hyperplastic polyps, and all but three adenomas and the adenomatous parts of the invading tumors did not show any epithelial cell positivity, and only occasional macrophages and fibroblasts showed weak cytoplasmic immunoreactivity for TP. Neoplastic cells in the carcinomatous part of the tumors were positive for TP in 18 out of 47 (36%) cases. Both nuclear and cytoplasmic staining was detected but in a few cases only one of these was present. There was a highly significant difference between TP expression in neoplastic epithelial cells in adenomas compared with carcinomas (p=0.0001). The same was true when the immunoreactivity of the stromal cells was compared (p=0.0001). Areas with high angiogenesis such as those at the invading edge of the tumor showed intense epithelial, endothelial and stromal TP immunoreactivity. These results show up-regulation of a major angiogenic pathway in both the tumor epithelium and stromal cells with progression from adenoma to carcinoma, and suggest TP may be a candidate target for therapy.
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PMID:Neoplastic stroma and epithelium show up-regulation of platelet-derived endothelial cell growth factor/thymidine phosphorylase in colorectal carcinomas but not adenomas. 1451 75

Most colorectal carcinomas (CRCs) arise from adenomas through an archetypal pathogenic pathway, the adenoma-carcinoma-metastasis sequence. Aberrant expression of beta-catenin, p16, E-cadherin and c-myc appears to have played important roles in the development and/or progression of CRC, but their precise distribution pattern and associations in different pathologic loci along CRC's pathogenic pathway have not been thoroughly examined. In this study, a tissue microarray (TMA) containing 85 advanced CRCs in different Dukes stages was constructed. In each of 85 cases, tissue specimens from normal mucosa and primary carcinomas in different layers of the bowel wall were included in the TMA. Tissue specimens from matched adenoma, lymph node metastases and distant metastases were obtained from 22, 21 and 21 cases, respectively. Expression patterns of beta-catenin, p16, E-cadherin and c-myc were evaluated by immunohistochemistry. The results revealed that nuclear expression of beta-catenin, p16 and c-myc was quantitatively increased from normal mucosa to premalignant adenoma, primary carcinoma and lymph node metastatic carcinoma; the frequency of nuclear overexpression of beta-catenin and p16 in lymph node metastases was significantly higher than that in distant metastases (p < 0.05). These results suggest an association between nuclear overexpression of beta-catenin and/or p16 and CRC lymph node metastasis but not distant metastasis. The results also showed that correlative high nuclear expression of beta-catenin and c-myc was observed in primary carcinomas involving the serosa and lymph node metastases (p < 0.05) but not in other pathologic regions of CRCs, suggesting that the tumor microenvironment in different pathologic loci of colorectal tumorigenesis and progression may influence c-myc responsiveness to beta-catenin/Tcf activation.
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PMID:Heterogeneous expression and association of beta-catenin, p16 and c-myc in multistage colorectal tumorigenesis and progression detected by tissue microarray. 1460 Oct 48

The aim of this study was to evaluate the potential application of 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) for colorectal cancer screening in asymptomatic individuals. The subjects consisted of 3210 physical check-up examinees (1736 men, 1474 women; mean age +/- SD, 53.2 +/- 8 y) with non-specific medical history. In the control group, 12 patients who had gastrointestinal symptoms with biopsy-proved colon carcinoma were recruited. Whole-body FDG PET was performed on all patients. Focal hypermetabolic areas with an intensity equal to or exceeding the level of FDG uptake in the brain and bladder were considered abnormal and interpreted as intraluminal neoplasia. Among the 3210 FDG PET examinations, advanced neoplasm was present in 20 examinations, including 2 tubular adenomas larger than 1 cm, 12 villous adenomas and 6 cancers. Of 6 examinees diagnosed with cancer, one had a Dukes stage A lesion, four had Dukes stage B lesion and one had a Dukes stage C lesion. In the control group, of 12 patients with biopsy-proved carcinoma followed by FDG PET scan, six had a Dukes stage B lesion, four had Dukes stage C lesion and two had a Dukes stage D lesion. The mean and standard deviation of standard uptake value (SUV) in colonic adenoma and carcinoma is 3.56 +/- 0.68 and 5.74 +/- 2.26, respectively. The sensitivity of using FDG PET in the detection of primary colorectal cancer is high. Primary colorectal cancer can be detected with FDG PET in a resectable stage. FDG PET could detect large size (> 0.7 cm) and pre-malignant change of colonic adenoma. It is possible to differentiate adenoma from carcinoma of colon by an increased rate of glycolysis (SUV) in carcinoma.
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PMID:Colorectal cancer screening in asymptomatic adults: the role of FDG PET scan. 1466 51

Two panning strategies have been used to isolate phage antibody clones that recognise an intracellular epitope of CD43. Firstly, a naive scFv library was panned against a 15-mer CD43 synthetic peptide (RGGKRNGVVDAWAGP), and secondly the naive library was panned against native CD43, isolated from whole cell lysate of Colo205 cells, followed by selection with the synthetic CD43 peptide. Four phage antibodies (HapE8, F2, G9 and G11) were isolated and used in a preliminary immunohistochemistry study of CD43 expression on frozen colorectal adenoma and carcinoma tissue. The three antibodies HapE8, F2 and G11 showed a similar reactivity pattern, staining all adenomas and Dukes' A carcinomas, but only 2/4 Dukes' B and 1/9 Dukes' C. Antibody HapG9 similarly bound to 5/5 adenomas, but only 1/5 Dukes' A carcinoma and no tumours of a more advanced stage. No reactivity with normal colonic epithelium was observed but cross-reactivity with stromal lymphocytes was seen. These new anti-CD43 antibodies are likely to prove useful as screening tools in the detection of colorectal adenomas.
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PMID:Novel CD43 specific phage antibodies react with early stage colorectal tumours. 1471 63

Lysosomal proteinases, cathepsin B (CB) and cathepsin D (CD) have been implicated in the progression of several human tumors. In the present study, the antigen levels of CB and CD, and their immunohistochemical staining were compared in paired colorectal tumors (n =64) and background colon tissue of the same patients with clinicopathological staging. The antigen levels, were found to be significantly higher in cancer tissue (mean 35.79 ng/mg protein for CB and 3.97 ng/mg protein for CD) than in corresponding normal mucosa (24.62 ng/mg protein for CB and 2.69 ng/mg protein for CD). CB antigen levels were positively correlated with differentiation grade and Duke's stage (P < 0.001 and P = 0.041, respectively), but not correlated with nodal status. CD antigen levels were not correlated with the previous parameters. Staining intensity for both antigens increased from adenoma to adenocarcinoma. The degree of staining for CB and CD was associated with differentiation grade (P = 0.004 and 0.001, respectively), Dukes' stage (P = 0.002 and 0.001, respectively) and lymph node involvement (P = 0.002 and P < 0.001, respectively).
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PMID:Cathepsin B and cathepsin D expression in the progression of colorectal adenoma to carcinoma. 1503 66


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