Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1326912 (tumorigenesis)
 57,481 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship of tumor size, status of disease in the TNM classification, and stage of disease to ras oncogene expression was studied in human non-small cell lung cancer materials immunohistochemically using monoclonal antibody rp-35 against ras 21. Materials of adenocarcinoma and squamous cell carcinoma obtained from primary sites larger than 30 mm in diameter exhibited intensely positive reactions with rp-35 significantly more frequently than those with primary sites, 30 mm in diameter or smaller (p less than 0.01). Furthermore in the TNM classification, cases with T2 (with primary sites larger than 30 mm in diameter) or T3 (with direct extension to adjacent structures) showed significantly higher reaction with rp-35 than those with T1 (with primary sites 30 mm in diameter or smaller) (p less than 0.01), although N and M status did not correlate with ras p21 expression. These results suggest that ras oncogene may play a significant role in growth or tumorigenesis at the primary site in human non-small cell lung cancer.
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PMID:The relationship of clinical classification to ras p21 expression in human non-small cell lung cancer. 284 11

Alterations in the p53 tumor suppressor gene are the most frequent genetic abnormalities in human cancers. The p53 protein is present in normal cells, and is assumed to induce G1 arrest or apoptosis in the presence of DNA lesion. The mutant protein lacks this property. Squamous cell carcinomas of the head and neck (SCCHN) are related to carcinogens in tobacco and alcohol, and provide a good model of multiple-step carcinogenesis in association with DNA damage and p53-related tumorigenesis. Stabilization of the mutant p53 protein allows immunohistochemical analyses (IHC) to be routinely used to demonstrate the mutant p53 protein in tissue samples, whereas normal p53 protein is undetectable. Ninety-nine squamous cell carcinomas, 8 in situ carcinomas, 31 preneoplastic lesions and 79 normal carcinogen-exposed mucosas of the head and neck from a total of 107 patients were examined for the expression of p53 tumor suppressor gene protein. Samples were collected before treatment, and stained with p53 specific mono- and polyclonal antibodies (DO-7, Pab 1801 and 240, CM1) using an indirect immunoperoxidase technique. Proliferating cell nuclear antigen (PCNA) provided semiquantitative estimates of proliferation. The main localizations were the pharynx (64/107) and the larynx (21/107). Positive IHC detection of p53 was observed in 9% of normal-appearing carcinogen-exposed mucosas, 37% of hyperplasias, 68% of dysplasias, 75% of in situ carcinomas, and 56/99 (56.5%) of primary tumor samples. Mucosas from 15 control patients under 10 years of age were negative. There was no correlation between p53 IHC and localization, differentiation or TNM staging.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunohistochemical detection of p53 protein in preneoplastic lesions and squamous cell carcinoma of the head and neck. 761 Aug 36

Cyclin D3, a cell cycle regulator, is encoded in the 6q21 chromosome region. Abnormalities of this gene and its protein product have not been found in normal tissues or in malignancies from human subjects. The expression of cyclin D3 was studied immunohistochemically in archival formalin-fixed, paraffin-embedded specimens from normal organs obtained from three autopsy cases and 237 human primary pulmonary carcinomas. In normal organs, nuclear positivity for cyclin D3 was observed in reactive type-2 pneumocytes, islets of Langerhans, lymphocytes from lymph nodes, superficial cells of transitional epithelium, epithelium of oesophagus, stomach, small intestine and gallbladder, endothelium, smooth muscles, and brain. Proliferating cells such as lymphocytes in the germinal centres and non-proliferating cells such as neurons both demonstrated cyclin D3 immunoreactivity. Cyclin D3 showed obvious nuclear immunoreactivity in 168 pulmonary carcinomas (71%). The proportion of tumour cells that were cyclin D3-positive ranged from 1% to 73% (median, 16%). There was no relationship between cyclin D3 immunoreactivity and histological typing, tumour differentiation, or pathological TNM staging. In pulmonary carcinomas, distinct expression of the cyclin D3 protein is unlikely to be implicated in tumorigenesis, because of its expression in only a small fraction of cancer cells. It may relate to cancer progression. The distribution of cyclin D3 reactivity in the normal tissues suggests that cyclin D3 affects other processes than cell cycle regulation in a lineage-specific manner.
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PMID:Immunohistochemistry of cyclin D3 in pulmonary carcinomas. 868 70

Previous studies have shown increasing evidence that TGF-alpha, a ligand for the often overexpressed EGF-receptor may be important for the oncogenesis and autocrine stimulation of the proliferation in head and neck cancers. The occurrence of TGF-alpha and its relation to the EGF-receptor still remain unclear. Twenty six specimens (primaries and metastasis) of oropharyngeal squamous cell carcinomas were investigated for the presence of transforming growth factor alpha (TGF-alpha), epidermal growth factor (EGF) and the EGF-receptor using a tissue extraction method and a "sandwich" immuno absorbent assay. In 77% of the specimens we found TGF-alpha, all had a significant amount of EGF-receptors, no EGF was found. No significant difference was noted for metastasis and primaries. No correlation was seen to the TNM stage and to the histological grading. There was an inverse statistical correlation between the TGF-alpha and the EGF-receptor concentration. High TGF-alpha concentrations were associated with low EGF-receptor concentration. Interestingly, even high TGF-alpha concentrations showed a lower limit of EGF-receptor concentrations which could not be passed. The present investigation gives a quantitative determination of the EGF-receptors and TGF-alpha in oropharyngeal carcinomas. The results indicate that a EGF-receptor/TGF-alpha complex could be functionally important for autocrine/paracrine stimulation.
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PMID:Correlation of transforming growth factor alpha and epidermal growth factor receptor in oropharyngeal carcinomas. 879 Jul 52

Apoptosis is considered to play a critical role in tumorigenesis. In order to clarify the significance of apoptosis in breast cancers, we quantitated apoptotic cells by light microscopy in 126 patients with invasive breast cancers. The expression of bcl-2, and p53, as regulators of apoptosis, was immunohistochemically analyzed. Apoptotic index (AI) detected in the patients ranged from 0 to 48 per mm2 of breast cancer cells (mean +/- SE, 11.0 +/- 0.97). Significantly highly AI was found for the tumors with grade 3 (p < 0.0001), high mitotic index (p < 0.0001), and bcl-2 negatively (p = 0.004) compared with those with grade 1 or 2, low mitotic index, and bcl-2 expression, respectively. Moreover, high AI was associated with larger tumor size (p = 0.008), positive lymph nodes (p = 0.01), p53 positivity (p = 0.01), and advanced TNM stage (p = 0.03). In survival analysis, we found that low AI, like bcl-2 and other conventional prognostic indicators, was significantly predictive of better prognosis in terms of both disease-free survival (DFS) and overall survival (OS) (each, p < 0.0001). In multivariate analysis, AI failed to retain an independent significant value for DFS or OS. Our results indicate that low AI is related to a number of clinicopathologic and biologic parameters known to predict a lower risk of recurrence and is associated with a favourable survival in invasive breast cancer. However, it was not an independent prognostic factor for clinical outcome in this patient series.
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PMID:Apoptotic index correlates to bcl-2 and p53 protein expression, histological grade and prognosis in invasive breast cancers. 967 55

The expression and coexpression of EGFR, c-erbB-2 and c-erbB-3 in 21 gastric cancers and 20 chronic gastritis was examined using immunohistochemistry on fresh frozen tissues considering clinicopathological variables. Generally, gastric cancer patients showed a higher incidence of EGFR, c-erbB-2 and d-erbB-3 overexpression than the group with chronic gastritis (81% and 43%; 38% and 45%; 35% and 20%, respectively), however, statistically significant differences were found only for EGFR expression (p = 0.01). No association between immunoreactivity of all growth factor receptors and the histopathological structure of gastric cancer was observed. EGFR and c-erbB-3 proteins were detected more frequently in patients with III/IV than in I/II of TNM stages, while c-erbB-2 overexpression was higher in I/II vs. III/IV stages. In chronic gastritis with intestinal metaplasia and or coexisting carcinoma lesions, a higher frequency of the expression of studied proteins was observed in comparison with chronic gastritis without those alternations; however, these differences were statistically insignificant. The percentage of positive cases with coexpression of two proteins was comparable in gastric cancer and chronic gastritis (33% and 35%) but the simultaneous expression of all three receptors was evident only in gastric cancer (19%). Our results indicate that at least one or two members of EGFR related receptors could appear in the early stages of gastric tumorigenesis. The enhancement of c-erbB-2 and c-erbB-3 reactivity seems to cooperate with EGFR activation in the gastric cancer development. Our results indicate the promotional rather than direct transformational role for EGFR supergene family in gastric carcinogenesis.
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PMID:Expression of epidermal growth factor receptor family proteins (EGFR, c-erbB-2 and c-erbB-3) in gastric cancer and chronic gastritis. 970 36

The cyclin-dependent kinase inhibitor p21/waf1 is regulated by p53-dependent and p53-independent pathways. In addition, mdm2 is an oncogene which forms an auto-regulatory loop with the normal p53 protein and its role has been implicated in oncogenesis. To determine whether a correlation exists between the expression of these gene products, tumor differentiation, tumor staging and radiation therapy, we investigated the expression of p21, p53 and mdm2, and cellular proliferation by Ki-67 (MIB1) labeling index using immunohistochemistry in 88 human oral squamous cell carcinoma (SCC) samples from 56 patients. Tumor expression of all nuclear proteins was scored according to the percentage of positive cancer nuclei, both with the cancer tissue as a whole as well as in different epithelial compartments of differentiation. Positive p21, p53, mdm2 and MIB1 staining was present in 82.4, 67.8, 25.9 and 98.8% of the SCC samples. The staining in different epithelial compartments of differentiation varied: those of p21 and mdm2 present predominantly in suprabasal and upper regions of the tumors: those of p53 and MIB1 in basal and suprabasal regions. Higher levels of p21 expression were seen in actively proliferating tumors (P = 0.025). p21 expression positively correlated with mdm2 expression but not with p53 expression. Moreover, the level of p21 expression was higher in older patients (P = 0.024) and female patients (P = 0.008). There was no significant association among p53, mdm2 and MIB1. Expression of p53 was higher in tumors with poorer cellular differentiation and in younger patients (P = 0.038 and 0.028). There was no association between tumor stage by TNM classification and the expression of any of these gene products or proliferation index. Radiation therapy did not alter the expression of any of these. To conclude, p21 protein was overexpressed in oral SCCs, and this overexpression was related to cell proliferation index and mdm2 expression but independent of p53 protein alteration. Overexpression of p21 alone appeared to be insufficient to suppress tumor progression.
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PMID:Expression of p21/waf1 in oral squamous cell carcinomas--correlation with p53 and mdm2 and cellular proliferation index. 1021 12

Molecular genetic studies have revealed mutations in a number of oncogenes and tumor suppressor genes in lung cancer. The bcl-2 gene product (bcl-2 protein) is implicated in oncogenesis by its ability to prolong cell death through the inhibition of apoptosis. We investigated expression of bcl-2 in 84 resected human non-small cell lung cancers (NSCLC) and correlated this phenomena with clinicopathology and survival. Immunohistochemical analysis with a monoclonal antibody specific for bcl-2 (Clone 124; Dako) was used to detect the protein in tumor samples. Overall, bcl-2 was detectable in 39 of 84 (46%) NSCLC. The percentage of bcl-2 positive cases varied according to the histological type. Positive bcl-2 immunostaining was observed in 27 of the 46 squamous cell carcinomas (59%), 7 of the 25 adenocarcinomas (28%) and 5 of the 13 large cell carcinomas (38%). The frequency of positive bcl-2 expression in squamous cell carcinomas was significantly higher than that in other histological two types (p = 0.037). Statistical comparisons between the patients' clinical characteristics and bcl-2 status revealed no significant differences in the frequency of bcl-2 expression with respect to sex, T and N factors, as well as TNM stage. The relationship between bcl-2 protein expression and postoperative survival was analyzed in 84 patients. Patients with bcl-2 negative tumors showed significantly shorter survival times than those with bcl-2 positive tumors. In univariate analysis of various potential prognostic factors only TNM stage and bcl-2 test were significant prognostic factors (p < 0.009 and p < 0.008, respectively). In multivariate analysis (Cox proportional hazard model), bcl-2 status (negative test) was independent unfavorable prognostic factor (p = 0.017). In conclusion, this set of observations suggests that assessment of the expression status of bcl-2 by tumors may provide prognostic information on the clinical behavior of NSCLC.
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PMID:Expression of bcl-2 protein in non-small cell lung cancer: correlation with clinicopathology and patient survival. 1035 30

In order to optimize the management of patients with renal cell carcinoma (RCC) it is important to define the genetic risk for metastatic disease. In this study we performed comparative genomic hybridization (CGH) on metastatic tumors aiming at the identification of genetic alterations associated with metastatic disease. We analyzed 46 renal tumors along with their metastases, and 15 non-metastatic renal tumors. Tumors were classified pathologically according to the Heidelberg classification of RCC, and staged according to the TNM-system. Standard CGH was performed using microdissected archival tissues and DOP-PCR. The average numbers of chromosomal aberrations per tumor were 3.0, 2.1 and 3.9 in patients without metastasis, in patients who developed metastases after a two-year latency period (late onset of metastatic disease) and in patients who developed metastases within two years after therapy of the primary tumor (early onset of metastatic disease). CGH revealed chromosomal aberrations in 91% of primary metastatic tumors. Deletions or losses of chromosomes 9 (26% vs 6%), 10 (21% vs 6%) and 18 (23% vs 0) and 17 (28% vs 7%) occurred more often in metastatic tumors than in non-metastatic tumors. Furthermore, these aberrations were more common in patients with early metastases. CGH analysis of 40 pairs of primary RCCs and their corresponding metastasis revealed similar aberrations in 70% of cases. In 30%, however, metastases showed additional chromosomal aberrations not detected in the corresponding primary tumors. In conclusion, we identified genetic alterations associated with metastatic disease in RCC which could be useful for predicting prognosis. Genetic changes leading to metastases occurred early in tumorigenesis of metastatic tumors.
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PMID:Genetic alterations in metastatic renal cell carcinoma detected by comparative genomic hybridization: correlation with clinical and histological data. 1102 90

Cyclin D1 is a set of periodic protein which governs G1 progression. Cyclin D1 gene is localized on chromosome 11q13 which encodes a 295-aa protein. Overexpression of cyclin D1 leads to abnormal cellular proliferation. Which underlies processes of tumorigenesis. In this paper twenty-five fresh specimens of laryngeal carcinomas were examined by means of immune flurescence technique. Overexpression of cyclin D1 was found in 9 of 16 laryngeal carcinomas (37%). There was no statistical correlation between overexpression of cyclin D1 and TNM staging, differentiation grading (P > 0.05). Normal tissue adjacent to tumors lacked any detectable cyclin D1 expression or rare scattered positive cells. It was likely that cyclin D1 overexpression wasn't an early event in processes of tumorigenesis and tumor progression. Follow-up investigation demonstrated that tumors recurred in 4 of 9 primary tumors overexpressing cyclin D1. But only 1 of 16 that expressed cyclin D1-negative. There was statistical significance between them, so overexpression of cyclin D1 could serve as a new prognostic marker.
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PMID:[Overexpression of cyclin D1 in laryngeal carcinomas]. 1118 54


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