Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Telomerase is a ribonucleoprotein enzyme which appears to play an important role in carcinogenesis. Telomerase reactivation seems to be associated with immortalization and malignancy. Using a PCR-based assay, we examined telomerase activity in 50 breast tissue specimens, prospectively obtained from 37 women undergoing elective breast surgery. The specimens examined included normal breast (n=13), benign breast lesions (n=5), ductal carcinoma in situ (n=8) and infiltrating ductal carcinoma (n=24). All normal breast, benign breast and DCIS specimens lacked telomerase activity. Sixteen (67%) of 24 infiltrating carcinomas. In infiltrating ductal cancer, there was a statistically significant association between telomerase activity and nodal metastasis. The present results indicate that telomerase activity is associated with acquisition of invasive malignancy in the human breast and may have a role in complementing cytopathological diagnosis. Telomerase activity as a prognostic marker should be included in future validation studies. In DCIS, telomerase activity may be a late event associated with invasion of the basement membrane.
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PMID:Telomerase activity in the human breast. 1473 43

An immunohistochemical study was performed of changes in the expression of adhesion molecule CD44 in 32 adjacent non-tumour epithelia (ANTE) to lingual carcinomas and in the tumour tissue, using anti-CD44 monoclonal antibody DF1485. The aim was to evaluate the importance of these changes as an early event in lingual carcinogenesis. The ANTE was histologically normal in 22 cases (68.8%) and presented epithelial dysplasia in 10 (32.2%). Three cases of normal and dysplastic ANTE, respectively, were CD44- (9.4%). Negative CD44 expression was significantly more frequent in tumours with lower percentages of CD44+ cancer cells, both in normal (P=0.014) and dysplastic (P=0.033) ANTE. The expression in normal ANTE was also significantly associated with clinical stage (P=0.040) and presence of extracapsular nodal spread (P=0.013). Therefore, loss of CD44 expression in ANTE can be considered an early event in lingual carcinogenesis and a marker of major alterations of CD44 expression in the derived tumour tissue.
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PMID:Adhesion molecule CD44 expression in non-tumour epithelium adjacent to tongue cancer. 1474 59

Cbl proteins play important roles in downregulation of growth factor receptors by acting as ubiquitin ligases and multi-adapter proteins. Ligand-induced desensitization of the epidermal growth factor receptor (EGFR) has been shown to be controlled by Cbl. In the present study, we examined the expression of Cbl in gastric carcinomas and studied the correlation of Cbl expression with clinicopathological characteristics as well as EGFR expression. Cbl protein was expressed in 67% (82/122) of gastric carcinomas, and diffuse expression of Cbl was detected in 29% (35/122) of the cases. The incidence of cases with diffuse expression of Cbl was significantly higher in advanced cases (28/70, 40%) than in early cases (7/52, 14%) (P=0.0010). Diffuse expression of Cbl was significantly associated with metastasis of tumor cells in lymph nodes (P=0.0318). Diffuse expression of EGFR was significantly associated with depth of invasion (P=0.0057), lymph-node metastasis (P=0.0371) and tumor stages (P=0.0278). As the grades of Cbl expression became stronger, the cases with diffuse EGFR expression increased, the positive correlation being significant (P=0.049). All the cases with diffuse expression of Cbl and EGFR were found to show nodal metastasis and to be at an advanced stage. Moreover, the prognosis of the patients with synchronous diffuse expression of Cbl and EGFR was significantly poorer than that of the patients negative for Cbl and focal or negative for EGFR (P=0.0086). The expression of Cbl protein was clearly induced in gastric carcinoma cell lines by transforming growth factor-alpha treatment. These results suggest that Cbl in connection with the EGFR system may be associated with stomach carcinogenesis, invasion and metastasis. Cbl may serve as a novel molecular marker for aggressive gastric carcinoma.
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PMID:Expression of Cbl linking with the epidermal growth factor receptor system is associated with tumor progression and poor prognosis of human gastric carcinoma. 1499 3

In colorectal tumors, S-phase kinase-associated protein 2 (Skp2) still has numerous important questions unanswered: its expression in adenomas, its correlation with key clinicopathological indices, its association with patient prognosis, its variation in lymph node metastases, and its association with many cell-cycle regulators. To answer these questions in colorectal tumors, Skp2, cyclin A, cyclin B1, cyclin E, CDK2, and Ki67 were immunohistochemically stained in 12 normal mucosa, 36 adenomas, 11 carcinomas in adenomas, 102 primary carcinomas, and 12 paired lymph node metastases; and Skp2 was examined by Western blot in 8 pairs of normal mucosa and carcinomas. Situated in nuclei, Skp2 expression significantly increased from normal mucosa through adenoma to primary carcinoma (p<0.0001), from mild through moderate to severe dysplasia in adenomas (p=0.038), from peripheral adenoma to paired central carcinoma (p=0.0033), and from primary carcinoma to lymph node metastasis (p=0.015), and these increases were confirmed by Western blot. Expression, however, relatively declined significantly in the primary carcinomas showing deep invasion (p=0.0113), lymph nodal metastases (p=0.0268), and poor prognosis for all (p=0.0104) or stage III patients (p=0.0119). High Skp2 was also significantly linked with elevated cyclin A, cyclin B1, cyclin E, CDK2 (in primary carcinomas only), and Ki67 in both adenomas and primary carcinomas. Thus, overexpression of Skp2 is associated with colorectal carcinogenesis and late metastasis to lymph nodes, whereas relative reduction of Skp2 is correlated with local invasion of primary carcinoma.
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PMID:Correlation of Skp2 with carcinogenesis, invasion, metastasis, and prognosis in colorectal tumors. 1520 93

E2F-1 is a pivotal transcription factor that integrates signals from a variety of G1/S phase regulators and modulates diverse cellular functions, such as DNA synthesis, repair, mitosis, and apoptosis. Its role in cellular proliferation and apoptosis, as depicted from experimental models and limited reports in human malignancies, remains a matter of debate. Recently, in non-small cell lung cancer, it was observed that E2F-1 overexpression was associated with tumour growth, implying an 'oncogenic' effect. To clarify further the role of E2F-1 in carcinogenesis, the investigation was expanded in four of the most common human malignancies by examining its expression status and putative impact on tumour kinetics. These issues were addressed by immunohistochemical and molecular means in 52 breast carcinomas, 42 prostate adenocarcinomas, 58 colon adenocarcinomas, and 77 superficial bladder transitional cell carcinomas (TCCs). The following results were found: (i). in breast carcinomas, E2F-1 expression correlated with proliferation (p < 0.001) and growth index (p = 0.001); (ii). in prostate adenocarcinomas, absence of E2F-1 was noted, in contrast to its expression in normal and hyperplastic glands; (iii). in colon adenocarcinomas, E2F-1 expression was inversely related to growth index (p = 0.001), being expressed in lesions with increased apoptosis (p = 0.001) and low proliferation (p < 0.001); and (iv) in superficial TCCs, E2F-1 expression correlated with proliferation (p = 0.002). Taken together, these results suggest that E2F-1 has a growth-promoting effect in breast carcinomas and superficial TCC, whereas the opposite seems to be the case for colon and prostate cancer. To interpret the above findings, the status of the pRb and p53 tumour suppressor pathways, which are known to affect E2F-1 activity, was further investigated. The results suggest that the actions of E2F-1 are mainly dependent on the functionality of these pathways. Nevertheless, the data also imply that p53-independent pathways may play a nodal role in the function of E2F-1 in colon cancer.
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PMID:Distinct expression patterns of the transcription factor E2F-1 in relation to tumour growth parameters in common human carcinomas. 1522 33

The epidermal growth factor receptor (EGFR) family plays an important role in breast carcinogenesis. Much interest has been focused recently on its members because of their potential role as prognostic indicators in breast cancer and their involvement in cancer therapy. We have evaluated more than 1500 cases of invasive breast carcinoma immunohistochemically using tissue microarray technology to examine the expression of EGFR family receptor proteins. We have found that 20.1 and 31.8% of cases were positive for EGFR and c-erbB-2, respectively, and 45 and 45.1% of tumours overexpressed for c-erbB-3 and c-erbB-4, respectively. The expression of either EGFR or c-erbB-2 was associated with other bad prognostic features and with poor outcome. Neither c-erbB-3 nor c-erbB-4 had any association with survival. c-erbB-2 had an independent prognostic effect on overall and disease-free survival (DFS) in all cases, as well as in the subset of breast carcinoma patients with nodal metastases. Several hetero- and homodimeric combinations have been reported between the EGFR members. Those dimers can evoke diverse signal transduction pathways with variable cellular responses. We stratified cases according to their co-expression of receptors into distinct groups with different receptor-positive combinations. Patients whose tumours co-expressed c-erbB-2 and c-erbB-3, as well as those whose tumours co-expressed EGFR, c-erbB-2 and c-erbB-4 showed an unfavourable outcome compared with other groups, while combined c-erbB-3 and c-erbB-4 expression was associated with a better outcome. In cases showing expression of one family member only (homodimers), we found a significant association between c-erbB-4 homodimer-expressing tumours and better DFS. In contrast, patients with c-erbB-2 homodimer-expressing tumours had a significant poorer DFS compared with other cases. These data imply that the combined profile expression patterns of the four receptor family members together provide more accurate information on the tumour behaviour than studying the expression of each receptor individually.
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PMID:Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma. 1548 Apr 34

The routine multidisciplinary management of colon cancer is based mainly on tumor staging, histology, grading and vascular invasion. In this approach, important individual information derived from molecular characteristics of the tumor may be missed, especially since significant heterogeneity of molecular aberrations in cancer cells has been observed, and recognition of every of relationships between them may be of value. K-RAS, C-MYC and C-ERBB2 are protooncogenes taking part in carcinogenesis and tumor progression in the colon. They influence cell proliferation, differentiation and survival. K-RAS point mutation, as well as amplification of C-MYC and C-ERBB2 were searched in 84 primary colon adenocarcinomas resected with curative intent. Multiplex polymerase-chain reaction and restriction fragment length polymorphism were performed to assess codon 12 K-RAS point mutation. Amplification of C-MYC and C-ERBB2 genes was evaluated by densitometry after agarose gel separation of the respective multiplex PCR products. No relation was found among mutated and/or amplified genes, and between searched molecular aberrations and pathoclinical features. In multivariate analysis, nodal status appeared to be the only independent prognostic indicator. In colon adenocarcinoma, codon 12 K-RAS point mutation and amplification of C-MYC and C-ERBB2 seem to occur independently in the process of tumor progression. Amplification of C-ERBB2 tends to associate with more advanced stage of disease. Concomitant occurrence of codon 12 K-RAS mutation, C-MYC and C-ERBB2 amplification was of no prognostic value in respect to survival.
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PMID:K-RAS point mutation, and amplification of C-MYC and C-ERBB2 in colon adenocarcinoma. 1549 79

The B-type Raf kinase (BRAF) protein is a serine/threonine kinase that has an important role in cellular proliferation, differentiation, and programmed cell death. The BRAF gene has been recently found to be mutated in human carcinomas, predominantly in malignant melanoma. The aim of this study was to investigate the frequency of the BRAF mutation in papillary thyroid carcinoma (PTC) of Koreans through direct DNA sequencing of the polymerase chain reaction (PCR)- amplified exon 15 with clinicopathological features. Seventy paraffin-embedded conventional papillary carcinomas in the thyroid gland were evaluated. The BRAF missense mutation at V599E was found in 58 of 70 PTCs (83%). The frequency of our series was much higher than the frequencies of other PTC series (36 - 69%). The frequency of nodal metastasis was also significantly higher in the BRAF mutation group (p= 0.048). These results suggest that the BRAF mutation is involved in the carcinogenesis in most conventional PTCs, especially those occurring in Koreans, and this is a potentially valuable marker for the evaluation of prognosis of patients with PTC. These findings support the specific inhibitors of BRAF being promising targets for the disease outcome.
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PMID:Mutations of the BRAF gene in papillary thyroid carcinoma in a Korean population. 1551 91

While HER2/neu receptor tyrosine kinase is involved in various malignancies, studies on colorectal adenocarcinoma (CRC) remain controversial. To try to clarify the role played by HER2/neu in CRC, sixty-seven CRC patients in Taiwan were analyzed. For this analysis, we used normalized dual-color fluorescence in situ hybridization (FISH) and Photoshop-aided immunohistochemistry (IHC) between cancers and their autologous non-neoplastic epithelia. The results revealed that HER2/neu status was unrelated to age, sex, location and positive-nodal percentage. Intramucosal carcinomas had earlier HER2/neu protein upregulation than regional stromal invasion within Dukes' A, and had a gene level that had not risen yet. Both gene gains and protein increases were significant in later stages in regards to volumetric progression and nodal-metastatic Dukes' stage. Overall, there were 1.53-fold (gene) and 1.81-fold (protein) increases from non-neoplastic enterocytes to CRCs. The upregulating directions of gene (88%) and protein (88%) presented symmetric agreement. Most CRCs exhibited low to intermediate levels of HER2/neu overexpression with double-minute gene amplicons and cytosolic HER2/neu proteins. Normalized FISH and IHC showed high cubic-regression correlation, especially in Dukes' C. According to the correlation curve, the points with IHC index >2.41 and FISH ratio >1.22 defined the area where gene-amplification-dependent HER2/neu overexpression was present. Eleven (16%) patients had values above the cut-off point (IHC = 2.41 and FISH = 1.22), including 7 (10%) cases in cytosolic and 4 (6%) cases in membranous HER2/neu overexpressions. The results suggest that HER2/neu plays a crucial role in CRC tumorigenicity with gene-amplification-independent transcriptional activations early in the carcinogenesis, and gene-amplification-dependent overexpression later in the advanced stages. This indicates that HER2/neu can be a good biological marker for selecting patients that may improve under therapies that employ adequate HER2/neu-targeting strategies.
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PMID:Clinicopathological relevance of HER2/neu and a related gene-protein cubic regression correlation in colorectal adenocarcinomas in Taiwan. 1575 87

ID4 gene is a member of the inhibitor of DNA-binding (ID) family, which inhibits DNA binding of basic helix-loop-helix transcription factors. Certain human primary breast cancers reportedly have low or no expression of ID4 protein, but its role in carcinogenesis and cancer progression is unknown. To determine its possible role, we examined epigenetic inactivation of ID4 gene by promoter hypermethylation in human breast cell lines and T1 breast cancer tissues. Methylation status of ID4 promoter CpG island was assessed by methylation-specific PCR (MSP); ID4 mRNA level was assessed by quantitative real-time RT-PCR. Of eight cell lines, two were fully methylated, four were partially methylated, and two were not methylated. ID4 mRNA level was suppressed in fully methylated cell lines. ID4 hypermethylation was observed in 16 of 24 (67%) node-positive and seven of 36 (19%) node-negative T1 primary breast cancers matched by patient age and tumor diameter. It was a significant risk factor for nodal metastasis (OR 13.1, P=0.0004). ID4 mRNA level was suppressed in hypermethylated cancer specimens (P=0.014). ID4 may play an important suppressive role in tumor progression, and its silencing by hypermethylation may increase the risk of regional lymph node metastasis.
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PMID:Aberrant hypermethylation of ID4 gene promoter region increases risk of lymph node metastasis in T1 breast cancer. 1589 10


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