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)

To evaluate the prognostic significance of immunohistochemically detected p53 and Bcl-2 proteins in colorectal cancer, tissue sections from 238 paraffin-embedded colorectal carcinomas were immunostained for p53 (MAb DO-7 and CM-1 antiserum) and Bcl-2 (MAb Bcl-2:124). Staining patterns were assessed semiquantitatively and correlated with each other and with sex, age, tumour site, Dukes' classification, tumour differentiation, mucinous characteristics, lymphocyte and eosinophilic granulocyte infiltration, and patient survival. In our series, 35% of carcinomas showed no nuclear staining and 34% (DO-7) to 40% (CM-1) showed staining in over 30% of tumour cell nuclei. A majority of carcinomas that had been immunostained with CM-1 showed cytoplasmic staining, but this was not observed with DO-7. With respect to Bcl-2, 51% of tumours were completely negative, 32% displayed weak and 15% moderate staining; only 3% showed strong positive staining. No evidence was found for reciprocity between Bcl-2 expression and nuclear p53 accumulation. From 13 cases containing tumour-associated adenoma, four were Bcl-2 negative in premalignant and malignant cells, in another four cases these cells showed similar staining intensities and in the remaining cases only the malignant colorectal cells were Bcl-2 negative. Therefore, our data indicate that Bcl-2 is dispensable in the progression towards carcinoma. Except for an association between nuclear p53 accumulation and mucinous tumours (P = 0.01), no significant correlation was found between the clinicopathological parameters mentioned above and immunostaining pattern of (nuclear or cytoplasmic) p53 or Bcl-2.
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PMID:Immunohistochemical detection of p53 and Bcl-2 in colorectal carcinoma: no evidence for prognostic significance. 966 56

Our aim was to study the relationship between the level of positivity of the Hemoccult colorectal cancer screening test and the positive predictive value on one hand, and the characteristics of the screened neoplasms on the other. This study focuses on four successive colorectal cancer screening campaigns in a population of 45,642 subjects born between 1914 and 1943. There were 1 or 2 positive slides in 50.1% of cases, 3 or 4 in 30.7% of cases and 5 or 6 in 19.2% of cases. The positive predictive value was 11.1% for cancer, 17.4% for adenoma > or = at 1 cm and 10.1% for adenoma < 1 cm. For a cancer or adenoma > or = at 1 cm, the positive predictive value varied between 18.6% when there were 1 or 2 positive slides, and 52.5% when there were 5 or 6 positive slides. Dukes A cancers are less likely to have 5 or 6 positive slides than more advanced cancers. On the contrary, neither cancer localisation nor characteristics of adenomas > or = at 1 cm (localisation, size, degree of dysplasia) influenced the number of positive slides. Owing to intermittent colorectal cancer bleeding, it seems necessary to take several successive samples. Two samples per stool over three successive stools seem like a good compromise. The informative value of the test increases with the number of positive slides.
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PMID:[Informative value of Hemoccult test according to the number of positive slides in mass screening of colorectal cancer]. 991 57

High mobility group I(Y) [HMGI(Y)] proteins are architectural factors abundantly expressed during embryogenesis, and their overexpression is known to be closely associated with neoplastic transformation of cells. This study was performed to investigate whether determination of HMGI(Y) expression level could assist in (a) differential diagnosis between colorectal carcinoma, adenoma, and normal tissue and (b) determination of the prognosis of patients with colorectal cancer. To this end, HMGI(Y) expression was determined at both the protein and mRNA levels in 30 colorectal carcinomas, 26 adenomas, and 23 normal mucosa samples, and further correlations between the protein expression levels and various clinicopathological parameters, such as depth of tumor invasion, lymphatic and/or venous involvement, regional lymph node metastasis, and Dukes' stage, were determined in 30 carcinoma cases. The expression of HMGI(Y) proteins was significantly increased in carcinoma and adenoma with severe atypia compared with that in adenoma with less atypia and normal colorectal mucosa. This increase in HMGI(Y) protein expression was found to be because of an increase in its mRNA expression by RNA in situ hybridization analysis. Clinicopathological analysis revealed that the level of HMGI(Y) protein expression was significantly correlated with parameters known to be indicative of a poor prognosis in colorectal cancer patients. These findings indicate that the determination of the HMGI(Y) protein expression level could be a potential marker for the diagnosis of colorectal neoplasias and can be of great value in predicting the prognosis of patients with colorectal cancer.
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PMID:Determination of high mobility group I(Y) expression level in colorectal neoplasias: a potential diagnostic marker. 1009 41

This study investigated the combined immunoexpression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in colorectal adenocarcinomas and correlated expression patterns with tumour stage and grade. Paraffin sections from 98 cases of colorectal adenocarcinomas were stained by immunohistochemistry for p53, p21, bcl-2, bax, Rb and MIB-1 (Ki67) proteins. In addition, 12 cases of colorectal adenomas and normal colorectal mucosa were studied in parallel. P53, p21, bcl-2, bax, Rb and Ki67 proteins were detected in at least 5% of tumour cells in 63/98, 72/98, 52/98, 96/98 and 98/98 adenocarcinomas, respectively. Comparative study of the normal-adenoma-carcinoma tissues revealed abrogation of the normal immunotopography in adenomas and adenocarcinomas, and considerable modifications, increase or reduction, of the expression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in adenocarcinomas when compared with normal mucosa and adenomas. Statistically significant correlations were found between low bax expression and Dukes C stage of carcinomas, Ki67 expression and carcinoma grade, and Ki67 and Rb expression. P53, p21, bcl-2 and Rb immunoexpression did not correlate with tumour stage or grade. Our findings show that low bax immunoexpression is frequently related to colorectal adenocarcinomas with lymph node metastases suggesting that low levels of bax expression play a role in late stage colorectal cancer. The correlation between Ki67 and Rb expression, in view of previous data that the hyperphosphorylated inactive Rb protein is frequently increased in colorectal adenocarcinomas, suggests that Rb protein is somewhat ineffective in inhibiting the cell-cycle progression in these malignancies. Furthermore, our findings provide immunohistochemical evidence that the abrogation of the normal immunotopography and the modifications of the expression of p53, p21, bcl-2, bax, Rb and Ki67 proteins reflect important events in colorectal oncogenesis.
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PMID:Expression of p53, p21/waf, bcl-2, bax, Rb and Ki67 proteins in colorectal adenocarcinomas. 1038 39

Regular administration of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the incidence of colorectal cancer by targeting cyclo-oxygenase-2 (Cox-2), a key enzyme in arachidonic acid metabolism. To evaluate the role of Cox-2 in sporadic colorectal cancer development, Cox-2 expression was investigated by immunohistochemistry in 85 adenomas, 53 carcinomas, 34 hyperplastic lesions and 104 samples of histologically normal mucosa adjacent to adenoma or carcinoma. In addition, Cox-2 mRNA expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) in six adenomas and 14 carcinomas with paired grossly normal mucosa. Immunohistochemistry for the proliferation-associated antigen Ki-67 and in situ end labelling for demonstrating apoptotic bodies were also used to analyse the associations between Cox-2 expression and proliferation and apoptosis. Cox-2 protein expression was increased in 76/85 (89.4 per cent) adenomas and 44/53 (83.0 per cent) carcinomas compared with normal mucosa. Cox-2 protein expression was unrelated either to the degree of dysplasia or to the size of the adenomas (p > 0.50, p > 0.10, respectively) or to differentiation, Dukes stage or lymph node metastasis of carcinomas (all p > 0.50). Interestingly, 20/34 (58.8 per cent) hyperplastic lesions adjacent to adenomas or carcinomas displayed expression higher than in normal mucosa (18.3 per cent) (p < 0.0001) but lower than in adenomas or carcinomas (p < 10(-5), p < 0.001, respectively). There were no correlations between Cox-2 protein expression and proliferative or apoptotic index in either adenomas or carcinomas (all p > 0.25). Cox-2 mRNA expression was significantly increased in adenomas and carcinomas compared with normal mucosa (p < 0.005, p < 0.001, respectively). There were no differences between adenomas and carcinomas in either protein or mRNA levels (p > 0.25, p > 0.90, respectively). These data indicate that enhanced expression of Cox-2 occurs early during colorectal carcinogenesis and may contribute to tumour formation.
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PMID:Early expression of cyclo-oxygenase-2 during sporadic colorectal carcinogenesis. 1039 82

The enzyme, thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF), which acts as a potent angiogenic factor. The present study immunohistochemically examined the expression of dThdPase in human colorectal mucosa, adenomas and carcinomas, as well as six cultured colorectal carcinoma cell lines, in terms of intratumoral microvessel density (IMVD) and P53 expression. Thymidine phosphorylase was observed in lymphocytes, fibroblasts and macrophages, as well as smooth muscle cells and Schwann cells in the peripheral nerve fibers. The dThdPase-positive stromal cells apparently outnumbered the normal epithelial cells, adenoma and carcinoma cells with dThdPase. Weak but obvious cytoplasmic immunoreactivity was noted in a few normal colonic epithelia, predominantly the upper surface area, while a few adenoma cells showed weak nuclear immunostaining for dThdPase in six (24%) of the 25 colonic adenomas. Expression of dThdPase was noted in 33 (73.3%) of the 45 Dukes A and B, 14 (51.9%) of the 27 Dukes C and 14 (56.0%) of the 25 Dukes D carcinomas. The mean IMVD was 84.0 +/- 26.2 in the 36 dThdPase-negative carcinomas and 97.9 +/- 31.6 in the 61 dThdPase-positive carcinomas, the value being significantly higher in the latter group (P < 0.05). The frequency of dThdPase expression was significantly lower in the P53-negative carcinomas than in the positive carcinomas (P < 0.05). Western blot analysis showed the highest expression of dThdPase in LoVo carrying the wild-type p53 gene, followed by Colo201, Colo320, DLD-11 and WiDr carrying the mutated gene. These results indicate that: (i) the main source of dThdPase is stromal cells, including lymphocytes and macrophages in both colorectal normal and carcinoma tissues; (ii) dThdPase may take part in the induction of intratumoral microvessels, regardless of tumor stage; and (iii) expression might be modulated by not only P53 but also other molecules.
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PMID:Thymidine phosphorylase expression in human colorectal mucosa, adenoma and carcinoma: role of p53 expression. 1046 91

The expression of S100A6 (also known as Calcyclin/2A9/ 5B10/PRA) in surgically resected human colorectal adenocarcinomas was examined to investigate whether S100A6 plays a role in the malignancy of human tumor cells. Western blot analysis using the lysates from colorectal adenocarcinomas and adjacent normal mucosa from 10 patients revealed that the average S100A6 level of adenocarcinomas was significantly higher (about 2.4-fold) than that of normal mucosa. Immunohistochemical analysis using formalin-fixed paraffin-embedded surgical specimens and monoclonal anti-S100A6 antibody (mAbA6) demonstrated that 2(5%) of 42 normal mucosa and 6 (46%) of 13 adenoma specimens were mAbA6-positive and showed granular staining localized at the supranuclear regions of epithelial cells, whereas 23 (55%) of 42 adenocarcinomas and 13 (100%) of 13 carcinoma cells that metastasized to the liver were mAbA6-positive and showed diffuse cytoplasmic staining. A significant correlation between S100A6 expression and Dukes' tumor stage or lymphatic permeation but not with other clinicopathological factors was shown. S100A6 was stained more intensely in peripheral portions than in central portions of adenocarcinomas, whereas Ki-67 (a growth marker) was stained equally in these two portions. These results suggest that S100A6 may be involved in the progression and invasive process of human colorectal adenocarcinomas.
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PMID:Increased expression of S100A6 (Calcyclin), a calcium-binding protein of the S100 family, in human colorectal adenocarcinomas. 1065 47

The overexpression of three growth factor receptors: epidermal growth factor receptor (EGFR), ERB B2 and ERB B3 was evaluated immunohistochemically in 77 malignant and 15 benign colorectal neoplasms considering clinicopathological variables (histological structure, grade of differentiation, tumor localization, clinical stage of the disease). The relationship between the coexpression of EGFR-related proteins in individual patients was also evaluated. EGFR expression was revealed in comparable percentages of colorectal adenoma and in adenocarcinoma cases (80% and 70%) while ERB B2 expression was detectable more frequently in adenoma than in adenocarcinoma cases (87% and 54%). The presence of ERB B3 was observed in a higher percentage of adenocarcinoma than adenoma cases (65% and 40%). There was no correlation between the expression of studied tyrosine kinase receptors and histological grade or Dukes' clinical stage and localization (proximal or distal) of colorectal adenocarcinoma. The incidence of EGFR and ERB B2 expression was higher in tubulovillous (100% for both receptors) than in tubular adenomas (63% and 75%), while the ERB B3 receptor was revealed more frequently in tubular than in tubulovillous neoplasms (50% and 28%). These differences appeared to be statistically nonsignificant. The concomitant expression of two growth factor receptors was observed in a higher percentage of colorectal adenomas than adenocarcinomas, and the coexistence of three growth factors was revealed in comparable percentages in malignant and benign colorectal tumors. Our results support the promotional rather than direct transformational role for the EGFR supergene family in colorectal tumorigenesis. The frequently observed coexpression of more than one EGFR-related protein in colorectal neoplasms indicates the possible cooperation of these receptors in mitogenic signaling transduction, facilitating the development and maintenance of the malignant phenotype.
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PMID:Expression of the tyrosine kinase activity growth factor receptors (EGFR, ERB B2, ERB B3) in colorectal adenocarcinomas and adenomas. 1068 40

Solid tumours require neovascularisation for growth and metastasis. Vascular endothelial growth factor (VEGF) has been shown to be an important regulator of tumour angiogenesis. To examine the relevance of VEGF in the neoplastic transformation of human colon, we analysed protein expression in a total 30 polyps and 145 colorectal carcinomas by immunohistochemistry. All adenoma specimens, regardless of histological differentiation, and normal colonic mucosa did not express VEGF. Amongst 90 patients with non-metastatic colorectal cancer, VEGF expression was observed in 43 (48%) cases, whilst 29 of the 55 patients (53%) with metastases expressed the angiogenic factor. Both the proportion and intensity of VEGF expression were positively associated with the progression of colon carcinogenesis. Tumours with the highest VEGF expression tended to correlate with patients' survival, although VEGF expression did not emerge as an independent risk factor in a multivariate analysis. After exclusion of the patients with distant metastases, both univariate and multivariate analysis did not indicate any prognostic value for the tissues with the highest VEGF expression. Our results suggest that VEGF may play a role in the progression of colon cancer, although evaluation of this angiogenic phenotype did not provide additional prognostic information compared with that obtained from Dukes' staging of the tumours.
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PMID:Prognostic value of vascular endothelial growth factor expression in colorectal cancer patients. 1076 47

Matrix metalloproteinases are considered to play an important role in tumor invasion and metastasis. To elucidate the involvement of MMP-1 in human colorectal carcinoma, we performed immunohistochemical analysis on tissues from 20 colorectal adenomas and 142 colorectal adenocarcinomas, including 27 intramucosal carcinomas and 115 invasive carcinomas. MMP-1 was not expressed in any of the 20 cases of colorectal adenoma examined. In contrast, 108 of 142 cases (76.1%) with colorectal adenocarcinoma showed immunoreactivity for MMP-1 in the carcinoma cells themselves. Expression of MMP-1 was also identified in stromal cells around the carcinoma. We investigated the relationship between pathological features in colorectal carcinoma and MMP-1 immunoreactivity of the tumor cells. MMP-1 expression was less frequent in intramucosal carcinomas and weaker than that in invasive carcinomas (P < .0001). Among the 115 cases of invasive carcinomas, MMP-1 immunoreactivity was significantly correlated with the depth grading of tumor invasion (P < .05), tumor growth pattern (P < .05), the presence of lymphatic invasion (P < .05), venous invasion (P < .05), neural invasion (P < .05), lymph node metastasis (P < .005), hepatic metastasis (P < .05), and increasing stages of Dukes' classification (P < .05). In situ hybridization, using an MMP-1 oligonucleotide probe, confirmed the presence of MMP-1 mRNA in colorectal carcinoma cells themselves. Expression of MMP-1 mRNA was detected by the reverse transcription polymerase chain reaction method in cultured human colorectal carcinoma cell lines and colon carcinoma tissue obtained at surgery. These findings suggest that the expression of MMP-1 is one of the important factors related to tumor invasion and metastasis in colorectal carcinoma.
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PMID:Expression of matrix metalloproteinase-1 in human colorectal carcinoma. 1100 31


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