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)

Mutations in the p53 tumour suppressor gene, with consequent accumulation of the p53 protein, are frequently observed in non-small cell lung cancer (NSCLC). Little is known, however, about the timing of their appearance or their maintenance through cancer progression and metastatic spread. We have examined the normal epithelium and a panel of bronchial lesions, including dysplastic, neoplastic, and metastatic lesions, for p53 immunoreactivity and for expression of proliferating cell nuclear antigen (PCNA). No p53 immunoreactivity was found in normal and hyperplastic epithelium, nor in squamous metaplastic lesions. Twenty out of 30 invasive tumours and 13 out of 17 in situ carcinomas adjacent to an invasive tumour showed p53 immunoreactivity. There was a strict correlation between the level of p53 expression in the non-invasive and the invasive components of the tumours. Five out of eight pairs of primary tumours and matching metastases expressed p53, at identical levels in both compartments. These data indicate that p53 overexpression can occur in the earliest recognized phase of NSCLC and that the alteration is maintained during progression from in situ to invasive carcinoma and metastatic spread. PCNA expression increased from early to advanced phases of NSCLC. High PCNA immunoreactivity was observed in tumours expressing high p53 levels. A significant association was observed for PCNA expression between preinvasive and invasive lesions.
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PMID:Human non-small cell lung cancer: p53 protein accumulation is an early event and persists during metastatic progression. 767 94

Head and neck squamous cell carcinoma has a relatively good prognosis but treatment may be at the expense of function and quality of life. Various host and tumour parameters have been studied in an attempt to predict the course of the disease but without success. It has been hoped that laboratory based methods, particularly those based on molecular biology, may prove more useful. Cell kinetic parameters are studied in this paper. The present study includes 75 patients with a proven squamous cell carcinoma of the head and neck at various sites and undergoing various forms of treatment. The patient's mean age was 62 years and the median survival rate 45 months. Immunohistochemical techniques using Ki67 and PCNA were compared with flow cytometric analysis which included the BRDU labelling index, the duration of S phase, ploidy and potential doubling time. The median PCNA index was 560 and the Ki67 index 298. These indices varied between 980 and 150 for PCNA and 808 and 110 for Ki67. The BRDU labelling index measured by flow cytometry was 8.9 with a range from 25 to 1.6 and the duration of S phase was 14.8 hours. The PCNA index failed to correlate with any host or tumour factors and this failure was also seen in Ki67 indices and also in the flow cytometric parameters. There was a strong correlation between PCNA and Ki67 expression (p < 0.0001). Neither PCNA nor Ki67 values were significantly different between irradiated and nonirradiated tissues nor in sites or in patients who later developed lymph node metastases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparison of cellular proliferation markers in squamous cell carcinoma of the head and neck. 798 34

The concept of cellular schwannoma as an unusual benign tumor is well established for peripheral nerves but has never been tested in neurosurgical series. In order to test the validity of this concept in cranial nerves and spinal roots we performed an analysis of the clinical and morphological characteristics of 12 cellular and 166 classical benign schwannomas. Immunohistochemical detection of antigen expression in Schwann cells including proliferating cell nuclear antigen (PCNA) was also performed. This study shows that cellular schwannomas in neurosurgical series manifest at a lower age than the classical benign variant and occur mainly in the spinal roots. Mitotic activity and sinusoidal vessels appear more frequently in cellular schwannomas and constitute with high cellularity, the most valuable criteria separating both entities. The postoperative course in both types of tumors was free of metastases or sarcomatous changes. Immunoexpression of S-100 protein, vimentin, epithelial membrane antigen and glial fibrillary acidic protein is not statistically different between the two variants. In contrast, PCNA is more highly expressed in cellular schwannomas. These These results confirm the concept that cellular schwannomas are a clinico-pathological variant of benign schwannomas and provide significant support for the introduction of this entity in neurosurgical oncology.
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PMID:Cellular schwannomas of the intracranial and intraspinal compartment: morphological and immunological characteristics compared with classical benign schwannomas. 809 64

Immunohistochemical detection of the nuclear antigen recognised by the monoclonal antibody Ki67, DNA polymerase alpha, and the proliferating cell nuclear antigen (PCNA), and histochemical staining for the argyrophilic proteins associated with the nucleolar organizer regions (AgNOR) were carried out on histological sections from 107 colorectal adenomas containing invasive carcinoma (ACIC), including 7 with regional lymph node metastases. Separate evaluations were made for fields corresponding to adenoma with low-grade dysplasia, adenoma with high-grade dysplasia and early cancer. The same techniques were also employed in 20 cases of normal mucosa and 20 advanced carcinomas. The mean percentages of Ki67, DNA polymerase alpha, and PCNA-positive nuclei and the number of AgNOR per nucleus progressively increased along the sequence from normal mucosa via low-grade and high-grade dysplasia adenoma to advanced cancer, whereas the early cancer values were not significantly different from those in the low-grade dysplasia areas. No significant difference in PCNA positivity and number of AgNOR were noted in ACIC with and without lymph node metastases. It is suggested that the decrease in proliferative activity thus revealed in early cancer may be due to changes in the submucosa microenvironment caused by invasion, and that the metastatic potential of an early colorectal cancer cannot be correlated to such activity.
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PMID:Cell proliferation in colorectal adenomas containing invasive carcinoma. 809 91

One-hundred and sixty-four patients with gastric carcinomas, who underwent gastrectomy during 1979-1985, were studied. Sixty-five of these cases were early gastric carcinomas, and the others were advanced gastric carcinomas, and the others were advanced gastric carcinomas. The nuclear DNA contents were measured by cytofluorometry, and immunohistochemical study on the expression of c-erbB-2 protein was performed using a monoclonal antibody against the c-erbB-2 oncogene product. Furthermore, immunohistochemical detection of proliferating cell nuclear antigen (PCNA) was performed using a monoclonal antibody against the PCNA. The rates of positive invasion beyond submucosal layer, lymphatic invasion, and vascular invasion in aneuploid cases were significantly higher than those in diploid ones, and the patients with aneuploid tumor had a significantly worse prognosis than those with diploid tumor. The rates of positive lymph node metastases and invasion beyond submucosal layer in the group with positive staining of the c-erbB-2 protein was significantly higher than in the negative group, and the group with positive staining for c-erbB-2 had a significantly worse prognosis than the negative one. PCNA indices showed a significant correlation with lymph node metastasis, and the group with higher PCNA indices had a worse prognosis. The patients with tumor showing both aneuploid and positive staining for c-erbB-2 protein, had the worst prognosis. There is a relationship between c-erbB-2 tissue status and PCNA indices, but no correlations were found among c-erbB-2 tissue status, PCNA indices and DNA contents. From these results, it can be concluded that DNA ploidy, c-erbB-2 protein, and PCNA may reflect the malignant potential of gastric carcinoma.
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PMID:[Correlation of DNA ploidy, c-erbB-2 protein tissue status, level of PCNA expression and clinical outcome in gastric carcinomas]. 809 98

p53 is a tumor suppressor gene, located in the short arm of chromosome 17, which encodes for a nuclear protein involved in the control of cellular growth. Mutations in p53 gene are the most common genetic alterations in a several human cancers, including Non Small Cell Lung Cancer (NSCLC). However, up to now, the role of p53 in the tumour's behaviour and its progression has not been completely clear. We performed immunohistochemical staining for mutated p53 using two monoclonal antibodies, PAb1801 and PAb240, in fresh tumour specimens from 103 consecutive patients who underwent surgery for resectable NSCLC. PAb1801 detects both the normal and mutant form of p53, while PAb240 is specific only for the mutant form and recognizes a denaturation-resistant epitope located between aminoacids 156-335. Both antibodies showed a mainly nuclear staining in neoplastic cells but not in surrounding uninvolved lung tissues. 68 out of 100 (68%) and 37 out of 103 (35.9%) of the cases were positive with PAb1801 and with PAb240, respectively. Tumours from patients with hilar-mediastinal lymph node involvement showed a higher p53 expression, detected by PAb1801, than those without nodal metastases (p = 0.04). Moreover, tumours expressing more than 60% of positive cells with both antibodies showed a significant increase of nodal involvement (p = 0.1; p = 0.03). Furthermore, p53 expression was significantly related to post-surgical stage (p Tumor Stage) (p = 0.04). In addition, we did not find any correlation between p53 expression and proliferating activity evaluated by PCNA, Ki-67 and DNA flow cytometric cell cycle. In conclusion, the evaluation of p53 oncogene expression may identify individuals whose resectable NSCLCs have a more aggressive tumour behaviour.
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PMID:p53 expression in non small cell lung cancer: clinical and biological correlations. 810 Apr 13

Expression of proliferating cell nuclear antigen, a DNA polymerase delta auxiliary protein, was studied in 20 specimens from 20 patients with conjunctival malignant melanoma by means of the total number of cells that showed immunoreactivity per square millimeter. The countings were shown to be reproducible with minimal intraobserver variability. In a multifactor analysis of variance (ANOVA) that adjusted for possible confounders, patients who subsequently died of metastatic disease had significantly higher counts of cells that were positive for proliferating cell nuclear antigen per square millimeter (P = .0011) than patients with a minimum survival of five years without clinical signs of metastatic disease. A multivariate Cox regression model confirmed the independent prognostic value (P = .048) of the cell counts. Individual hazard ratios were estimated in a final Cox model and two groups of patients with low and high hazard ratios were formed. Five-year cumulated survival proportions of the two groups were 90% and 60%, respectively. The total count of cells displaying immunoreactivity for proliferating cell nuclear antigen per square millimeter may be used as a prognostic indicator in patients with conjunctival melanoma.
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PMID:Cell proliferation as a prognostic indicator in conjunctival malignant melanoma. 810 Oct 47

Clinicopathological and immunohistochemical analyses were performed on ten samples of gastrointestinal carcinoids resected in Ishikawa Prefectural Central Hospital. All samples showed positive reaction to chromogranin A. Serotonin was detected in 8 samples, somatostatin in 4 samples, gastrin in 2 samples. Glucagon/Glicentin in 1 sample, and PYY production in 2 samples. CEA production was detected in 8 samples, and microvascular invasion was observed in 6 of these 8 patients. The PCNA/cyclin labeling index (L.I.) of the cases with metastases was significantly higher than those without metastases. In conclusion, the expression of CEA and the PCNA/cyclin L.I. may be useful markers of the malignant potential of carcinoid tumors.
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PMID:Immunohistochemical analysis of gastrointestinal carcinoids. 810 55

Morphologic studies of gastric stromal tumors (GSTs) indicate that mitotic counts (MCs) and tumor size are major discriminants predictive of biologic behavior. The authors evaluated the tumor proliferation of GSTs with anti-proliferating cell nuclear antigen (PCNA; DAKO clone PC10, DAKO Corporation, Carpinteria, CA) for correlation with MCs, histologic cell type, and clinical outcome. Fifty-eight tumors ranging from 1.5 to 45 cm in size were selected for clinicopathologic assessment. Mitotic activity was counted per 50 high-power fields (MC). For this study, combined parameters of MC and tumor size were used to categorize tumors into three groups: (1) benign: MC less than 5, tumor smaller than 5 cm; (2) borderline: MC less than 5, tumor larger than 5 cm; and (3) malignant: MC greater than 5, tumor any size. The PCNA tumor proliferation index (TPI) was assessed from evaluation of 200 tumor cells per case and expressed as the percentage of cells with positive results. Clinical follow-up was available in 45 cases. None of the 19 benign or 16 borderline tumors recurred or metastasized, whereas 7 of 10 malignant tumors metastasized and 1 of 10 recurred. The mean PCNA TPI values among benign (11.2%), borderline (16%), and malignant (34.5%) tumors were significantly different (P = 0.0002, Kruskal-Wallis test). When the pathologic tumor categories were compared, the mean TPI of benign tumors was significantly different from that of borderline tumors (P = 0.0306, Kruskal-Wallis), and the TPI of borderline tumors was different from that of the malignant tumors (P = 0.0060, Kruskal-Wallis test). The Spearman rank correlation showed a significant relationship between the MC and PCNA TPI (P = 0.0003, r = 0.4543). Logistic regression analysis showed that the TPI, independent of MC and size, contributed significantly (P = 0.00295) to the prediction of outcome. In the malignant group, the mean TPI for malignant tumors with metastases (43.6%) was significantly different (P = 0.0411, Kruskal-Wallis test) from that of malignant tumors without metastases (including the case with probable recurrence) (11.83%). No correlation was found when PCNA TPIs for epithelioid GCTs were compared with those of spindle cell GSTs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prognostic value of proliferating cell nuclear antigen index in gastric stromal tumors. Correlation with mitotic count and clinical outcome. 810 76

The aim of this study was to evaluate the power of quantitative pathology in improving the accuracy of prognosis in ductal infiltrating breast carcinoma. Ninety tumours were studied, with a diameter < or = 2.5 cm; positive (metastatic) axillary lymph nodes were found in 48 of the 90 cases; no patient had systemic metastases. Surviving patients had a mean follow-up of 106 months (minimum 69 months). At the end of the study, 45 patients were alive, 45 deceased. The histopathologic study of tumour nuclei and nucleoli included: a) geometric features, i.e., the mean and standard deviation of nuclear area, perimeter, diameter and form factor, nucleolar area and nucleolar/nuclear ratio, measured with a Kontron-IBAS automatic image analyser; b) immunohistochemical features, i.e., the percentage of PCNA (Proliferating Cell Nuclear Antigen)-positive nuclei, the expression (positive or negative) of vimentin (as a marker of tumour dedifferentiation), and the nuclear protein p53. Statistically significant differences were found between surviving and decreased patients for most features; multivariate analysis gave 92.2% accuracy in predicting outcome. Among the classes defined with multivariate analysis, it was possible to distinguish subsets of patients with bad prognosis by studying the expression of vimentin and p53, although these markers were positive in a small number of cases: 5 out of 6 patients with vimentin positivity and 4 out of 8 with p53 positivity died within 24 months of the diagnosis.
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PMID:Multivariate quantitative histopathological assessment of prognostic factors in ductal infiltrating breast carcinoma. 810 96


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