Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-small-cell lung cancer (NSCLC) prognosis is strictly related to well-established clinicopathological parameters which have unfortunately become insufficient in the prognostic evaluation of this type of cancer. As p53 and bcl-2 gene deregulations are frequently involved in several types of epithelial malignancies, we investigated the Bcl-2 and p53 protein expression in 91 and 101 cases of NSCLC respectively. The expression was then compared with established indicators of prognosis and biological behaviour of the tumours. No relationship was observed between Bcl-2 and either clinicopathological or biological parameters such as histology, grading, tumour status, nodal metastasis and proliferative activity evaluated by scoring proliferating cell nuclear antigen expression and Ki-67 immunoreactivity. However, the mean Bcl-2 expression was significantly lower in patients who developed metastasis during follow-up or died of metastatic disease (P = 0.006 and P = 0.01 respectively). Moreover, survival probability was higher in patients who expressed the Bcl-2 protein (P = 0.0002). In contrast with this, p53 protein accumulation was observed in tumours with metastatic nodal involvement (P = 0.02) or in patients who developed metastasis during follow-up (P = 0.01), although no correlation was found between p53 expression and overall survival. An inverse relationship was also found between Bcl-2 and the anti-oncogene protein product p53 (P = 0.01). Thus, a high proportion of NSCLCs express p53 and Bcl-2 proteins and their expression may have prognostic importance.
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PMID:Bcl-2 protein: a prognostic factor inversely correlated to p53 in non-small-cell lung cancer. 773 90

Cytologic specimens (FNA) from 42 primary invasive ductal breast carcinomas and 22 matched specimens of cancer tissue were tested for EGFR status, PCNA index and vimentin expression by immunocytochemical staining, using an Extravidin-Biotin method, and their relationship with various prognostic factors was investigated. EGFR positivity, high PC10 score and vimentin positivity were significantly correlated with high histologic grade. The coordinate expression of EGFR, PCNA and vimentin was significantly associated with ER-negative breast carcinomas. A positive trend was observed between high proliferating tumours and EGFR expression. EGFR status and PCNA index were not correlated with axillary lymph node involvement, tumour size, age and menopausal status. Vimentin was preferentially expressed in tumours, with lymph node metastases. Co-expression of EGFR, PCNA and vimentin was determined in most cases. These data suggest that EGFR status, PCNA index and vimentin expression may be important for the prediction of biologically aggressive tumours.
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PMID:Relationship of epidermal growth factor receptor (EGFR), proliferating cell nuclear antigen (PCNA) and vimentin expression and various prognostic factors in breast cancer patients. 773 97

DNA nuclear content and PCNA index (proportion of PCNA reactive cells) have been studied by flow cytometry in eight pancreatic lesions producing hyperinsulinemic hypoglycemia to assess DNA ploidy and tumoral growth fraction. Adult nesidioblastosis had a diploid DNA index, two adenomas were near diploid, and four of the adenomas and the carcinoma were aneuploid. The median value of PCNA index (6.056% +/- 6.76) was significantly correlated (P < 0.05) with the mean tumor diameter (2.43 cm +/- 1.96). Tumors with a PCNA index < 6.056% showed a diameter less than the mean tumoral diameter and a benign clinical course. Tumors with PCNA index > 6.056% generally displayed a diameter bigger than the mean tumoral diameter, being associated with lymph node metastases in one case. The authors conclude that nuclear DNA and PCNA index cytometric studies are useful parameters to assess the biological behavior of pancreatic lesions producing hyperinsulinemic hypoglycemia.
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PMID:DNA ploidy and PCNA index in pancreatic lesions producing hyperinsulinemic hypoglycemia. 774 70

Although patients with superficial bladder cancer (Ta, T1) have a generally good prognosis, those of them who have tumours invading muscle or metastatic disease will have a poor clinical prognosis. In the current study, 41 patients undergoing complete transurethral resection for superficial transitional cell cancer of the bladder were investigated for different clinical and biological characteristics as possible prognostic factors: age, sex, previous instillation therapy, immunohistochemical determination of mutational inactivation of p53 tumour suppressor gene (monoclonal antibody pAb 1801) and proliferation rate determined immunohistochemically by staining for PCNA (proliferating cell nuclear antigen; monoclonal antibody PC 10). After a median follow-up of 54 months 7 of 8 patients (87.5%) with more than 20% of cells positive for p53 had disease recurrence, as against only 1 of 33 patients (3%) negative for p53 detection (P < 0.01; Chi-square test). During univariate analysis histological grade (G1 vs G2; P = 0.007), positivity for PCNA (> 60% of cells; P = 0.003) and positivity for p53 (P = 0.001) were significant prognostic factors for disease progression (log rank test), while during multivariate analysis only positivity for p53 was a significant predictor for relapse of bladder cancer (P = 0.0035; multivariate Cox regression analysis).
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PMID:[Value of the proliferation status (PCNA) and p53 immunohistochemistry as a prognostic factor for the clinical course of superficial cancer of the urinary bladder]. 775 87

Based upon a group of 108 consecutive mammary carcinomas a comparative analysis of morphological parameters, DNA-ploidy and indicators of proliferation activity was made. A correlation between Bloom-Richardson scale, mitotic index, PCNA-labeling index and DNA-index was shown. The ploidy of mammary carcinomas was significantly related to the values of proliferative fraction, as well as to PCNA-labeling index. Among patients with axillary metastases the tumor size and the value of PCNA-labeling index were significantly higher than those in patients with negative lymph nodes.
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PMID:Relationship of histology, DNA-values and proliferative activity in unselected breast cancer patients (a preliminary study). 778 Jun 93

Robson stage I or II renal carcinomas have a heterogenous clinical outcome. A variety of morphologic features and other parameters have been proposed as prognostically useful. The authors measured the DNA content and PCNA expression of 47 stage I or II renal carcinomas, and assessed the association of these measures with pathologic stage, nuclear grade, and clinical course. Approximately 56% of stage I neoplasms and 40% of stage II neoplasms were diploid. Five of 9 neoplasms in which multiple samples were analyzed manifested both aneuploid and diploid regions. PCNA expression was noted in 20 of 32 stage I neoplasms and 9 of 15 stage II neoplasms, and varied greatly among the neoplasms. Neither ploidy nor PCNA expression is associated with clinical behavior in these data. These results are different from some of those previously reported by others. These discrepancies are likely to be due to differences in methodology and the fact that there were only eight cases of metastatic disease. No single parameter will serve as a completely accurate prognostic indicator. Most individuals with these neoplasms will do well because all of the tumor has been excised.
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PMID:DNA and PCNA content of renal cell carcinoma and prognosis. 781 36

Although patients with superficial bladder cancer (Ta, T1) have a generally good prognosis, those patients who develop muscle-invasive tumours or metastatic disease at recurrence do poorly clinically. In the current study 69 patients undergoing complete transurethral resection for superficial transitional cell cancer of the bladder were investigated for different clinical and biological characteristics as possible prognostic factors: age, sex, performance of instillation therapy and immunohistochemical determination of mutational inactivation of p53 tumour-suppressor gene (monoclonal antibody PAb 1801) as well as immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating cell nuclear antigen) (monoclonal antibody PC 10). After a median follow-up of 45.8 months, 12 of 14 patients (85.7%) with more than 20% of cells positive for p53 had disease progression with muscle-invasive growth compared with only one of 55 patients (1.8%) negative for p53 (P < 0.01, chi 2 test). During univariate analysis histological grade (G1 vs G2) (P = 0.0373), positivity for PCNA (> 60% of cells) (P = 0.0033) and positivity for p53 (P < 0.001) were significant prognostic factors for disease progression (log-rank test), while during multivariate analysis only positivity for p53 was a significant predictor for relapse of bladder cancer (P = 0.0029) (multivariate Cox regression analysis). The immunohistochemical detection of mutations of the p53 gene has been demonstrated to be a reliable, easily performed and thereby widely available technique for the investigation of fresh-frozen or paraffin-embedded tumour specimens. The results demonstrate the important role of the p53 tumour-suppressor gene protein in the development and for the progression of bladder cancer. If the high prognostic value of p53 mutations in superficial bladder cancer is confirmed in larger prospective trials, more aggressive therapeutic strategies could be discussed for patients with p53 mutations in their tumour specimens.
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PMID:p53 immunohistochemistry as an independent prognostic factor for superficial transitional cell carcinoma of the bladder. 781 40

In this study we investigated 56 renal cell carcinomas immunohistochemically for the expression of proliferating cell nuclear antigen (PCNA) and tumour suppressor protein p53. We also analyzed for the presence of human papilloma virus (HPV) DNA subtypes 6, 11, 16, 18, 31 and 33 by in situ hybridization. In carcinomas which showed more than 10% of PCNA positive nuclei there were significantly more cases with invasion (P = 0.032) or metastatic disease (P = 0.047). Nine out of 22 grade III-IV tumours (40.9%) but only six out of 30 grade I-II tumours (20%) showed more than 10% of PCNA positive cells (P = 0.097). Patients with 10% or more PCNA positive cells in kidney tumours had more advanced disease at the time of diagnosis than those showing less PCNA positive cells (P = 0.05). Six p53 positive cases were found among 56 tumours (11%), but only one case had more than 10% positive cell nuclei. The presence of HPV DNA was found in 29 out of 56 cases (52%). Multiple subtypes were found in 19 cases (34%). The most commonly occurring subtypes were 18 and 33. There was no association between PCNA, p53 and the presence of HPV DNA subtypes. Because of the association of PCNA with invasion and metastatic disease, it would be worth while to study PCNA further as a possible marker for aggressiveness of renal carcinomas. Both this study and those concentrated on mutational analysis suggest that p53 is generally not important for the development of renal cell carcinoma. On the other hand, the presence of HPV DNA in these tumours implicates HPV viral infection in the aetiology of renal cancer.
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PMID:Proliferating cell nuclear antigen but not p53 or human papillomavirus DNA correlates with advanced clinical stage in renal cell carcinoma. 783 39

An increasing body of evidence suggests that in addition to conventional histopathologic tumor characteristics, DNA content measurements, cell kinetic data, and investigations of tumor suppressor gene expressions might be of valuable information in breast cancer patients. Against this background we investigated immunohistochemically overexpression of the interphase associated protein proliferating cell nuclear antigen (PCNA) and the mutant p53 protein in routinely paraffin-embedded surgical specimens from 180 breast cancer patients with known nuclear DNA profiles. The mean clinical follow-up was 16 years (range 13-20 years). The percentage of PCNA immunoreactive tumor cell nuclei ranged between < 5% and 60% (mean 13.59 +/- 10.85%). There was a direct association between high levels of PCNA expression (> 20%) and p53 protein overexpression (p = 0.001), high histologic tumor grade (p = 0.009), and DNA aneuploidy (p = 0.019). Mutant p53 protein overexpression was found in 44 of 180 (24%) cases and was significantly related to high histologic tumor grade (p = 0.004), DNA aneuploidy (p = 0.001), and high levels of PCNA expression (p = 0.001). Patients with highly proliferative carcinomas (> 20% PCNA expression) had a shortened distant metastases-free survival when their neoplasms overexpressed p53. In contrast, the distant metastases-free survival of patients with highly proliferative, p53-negative tumors was significantly longer (p = 0.03). Immunohistochemical p53 protein overexpression thus appears to be indicative of an increased malignant potential in breast cancer patients. Highly proliferative tumors composed of p53 immunoreactive neoplastic cells clinically seem to behave more aggressively than the highly proliferative p53-negative tumors.
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PMID:Association of immunohistochemical p53 tumor suppressor gene protein overexpression with prognosis in highly proliferative human mammary adenocarcinomas. 784 4

To examine the malignant potential of submucosal invasive colorectal carcinoma, the relationship between proliferating cell nuclear antigen (PCNA) expression and clinicopathologic risk factors for lymph node metastasis was studied in 149 patients with submucosal invasive colorectal carcinoma. The depth of submucosal invasion was classified as scanty or massive. Histologic subclassification at the submucosal deepest invasive portion was done as follows: well differentiated (W), moderately well differentiated (Mw), moderately poorly differentiated (Mp) or poorly differentiated (Por). Tumor growth was divided into polypoid growth and nonpolypoid growth. The PCNA expression (labeling index, LI) was examined at the submucosal deepest invasive portion. The PCNA-LI of tumors showing lymph node metastasis (mean, 56.5 +/- 19.0%) was significantly higher than that of tumors without lymph node metastasis (mean, 41.5 +/- 19.3%; p < 0.01). The PCNA-LI of Mp tumors (mean, 57.7 +/- 16.5%) was significantly higher than that of W (mean, 38.5 +/- 19.0%; p < 0.05) and Mw (mean, 43.7 +/- 19.1%; p < 0.05) tumors. The PCNA-LI of tumors without adenomatous features (mean, 47.9 +/- 20.5%) was significantly higher than that of tumors with such features (mean, 37.1 +/- 17.1%; p < 0.05). The PCNA-LI was not correlated with other risk factors for lymph node metastasis, such as lymphatic invasion, depth of submucosal invasion, macroscopic type, and growth pattern. These results indicate that the PCNA-LI may be useful marker for predicting the potential metastases to lymph nodes in submucosal invasive colorectal carcinoma, while the proliferative activity of cancer cells correlates with the degree of the differentiation in the area of deepest invasion.
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PMID:Proliferating cell nuclear antigen expression correlates with the metastatic potential of submucosal invasive colorectal carcinoma. 785 73


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