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)

The aim of this study is to investigate the predictive value of proliferative activity assessment and E-cadherin expression by means of immunohistochemistry in identifying patients with laryngeal squamous cell carcinoma at a high risk for occult node metastasis. Thirty consecutive patients treated for laryngeal carcinoma with false clinically negative nodes (occult metastases, pN+) between the years 1980 and 1990 were selected for this study. A group of 30 cases with negative cervical lymph nodes (pN-) having a similar anatomic site and tumor size distribution was used as control. In each case, several histological parameters, including grade, pattern of invasion, number of mitosis (x10 high-power field), tumor inflammatory infiltrate, and tumor sclerosis, were assessed. Proliferative activity was determined using immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and MIB-1. Other putative prognostic factors investigated at the immunohistochemical level were the cell adhesion molecule E-cadherin and two oncoproteins, p53 and c-erbB-2. In pN+ cases, the expression of PCNA and MIB-1 was significantly higher than in the pN- group. Moreover, a significant loss of E-cadherin expression was observed in carcinomas with occult metastases. No differences in p53 and c-erbB-2 oncoproteins were found between pN+ and pN- cases. Among the other pathological parameters examined, only histological grade was significantly associated with the presence of occult metastases, but on multivariate analysis, this relationship was lost. We conclude that PCNA, MIB-1, and E-cadherin are independent predictors of occult nodal disease in laryngeal squamous cell carcinoma, and their immunohistochemical determination could be useful in identifying patients with clinically negative lymph nodes who are at considerable risk for occult metastases and who may benefit from elective neck dissection.
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PMID:Prediction of occult neck metastases in laryngeal carcinoma: role of proliferating cell nuclear antigen, MIB-1, and E-cadherin immunohistochemical determination. 981 33

Immunohistochemical detection of cell proliferation-associated antigens was investigated in 28 cases of adenoid cystic carcinoma (ACC) and 20 cases of pleomorphic adenoma (PA), using antibodies against DNA topoisomerase type II alpha (topo-II) (Ki-S1) and Ki-67 (MIB-1). The correlation of staining indices with clinicopathological data, histological features and prognosis was also studied. The topo-II value was significantly higher in ACC than in PA (P<0.0001), and highest in the solid growth pattern of ACC. In addition, significant relationships were found between topo-II values and clinical features such as local recurrence, surgical margins, and distant metastases. By log-rank test, the topo-II index was also correlated significantly with patient survival (P<0.01). The values of topo-II index paralleled those of Ki-67 index in ACC, and a correlation coefficient of 0.97 was obtained. Topo-II may be considered an additional marker for estimating the proliferating fraction of cells and for predicting the short-term prognosis for patients with salivary gland tumors.
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PMID:Immunohistochemical detection of DNA topoisomerase type II alpha and Ki-67 in adenoid cystic carcinoma and pleomorphic adenoma of the salivary gland. 1006 42

The proliferative index detected immunohistochemically by monoclonal antibody MIB-1 from pre-treatment biopsy tissues of 33 patients with esophageal squamous cell carcinoma who underwent preoperative concurrent chemoradiotherapy was evaluated in relation to clinicopathologic features and chemoradiotherapeutic responses. The response to chemoradiotherapy was assessed both endoscopically and pathologically and classified as complete or partial response. Higher MIB-1 LI was significantly associated with lymph node metastases, suggesting that detection of MIB-1 LI from biopsy tissues may contribute to pre-treatment staging of tumors and prediction of persistence of lymph node involvement after chemoradiotherapy, which would permit the optimization of systemic treatment for individual patients. Statistically, significant correlation existed between higher MIB 1-LI and poor overall survival, implicating the prognostic significance of the MIB-1 LI in patients undergoing multimodality treatment. No significant relationship was found between the MIB-1 LI and either endoscopic or pathologic responses, although a trend for tumors with lower MIB-1 LI to have better responses was observed.
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PMID:The utility of the proliferative index in pretreatment biopsy specimens of esophageal squamous cell carcinoma. 1007 1

The stomach is the most common gastrointestinal site of mesenchymal tumors which traditionally have been designated as smooth muscle tumors. However, with increasing analytic tools most investigators were unable to demonstrate true myogenic differentiation. Furthermore, the biological behavior of gastrointestinal stromal tumors (GIST) is difficult to predict. The aim of this study was to evaluate MIB-1 and p53 as additional prognostic markers, as well as myogenic differentiation immunohistochemically in GIST. 43 gastric stromal tumors were reviewed, 19 were classified as benign, and 10 as malignant. 14 tumors were considered indeterminate for biological behavior. In addition to MIB-1 and p53, immunohistochemistry was also performed for sm-actin, desmin and S 100-protein (ABC). 41 patients had a clinical follow-up of more than 2.5 years, 5 patients had metastases. Mean proliferation rates defined as percentage of MIB-1 positive tumor cells in 3 HPF were as follows: typical leiomyoma: 0.2%; benign GIST, spindle cell type: 1.8%; benign GIST, epithelioid cell type: 2.4%; borderline GIST, spindle cell type: 2.1%; borderline GIST, epithelioid cell type: 2.5%; malignant GIST, spindle cell type: 4.9%; and malignant GIST, epithelioid cell type: 7.3%. All 5 metastasizing tumors had a proliferation index > 4% (p < 0.0001). 4/5 metastasizing tumors had p53 positive cells (p < 0.05). 36/43 tumors were sm-actin positive, 7 of which were positive for desmin as well. Classification of gastric mesenchymal tumors as GIST is appropriate because only a small percentage show true smooth muscle differentiation. A MIB-1 proliferation index above 4% might indicate a more aggressive course, as well as p53 positivity.
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PMID:[Prognostic factors of gastrointestinal stromal tumors of the stomach]. 1009 44

Purpose of our study was to develop a reliable model to define clinical stage I nonseminomatous germ cell tumors (NSGCT) being at low risk and at high risk for occult retroperitoneal metastases based on pathohistological and immunohistochemical parameters in order to stratify the therapeutic approach. 3-5 paraffin-embedded formalin fixed tissue blocks of 149 clinical stage I NSGCT were available from all patients and were analyzed for histopathological features associated with pathological stage: presence/absence of vascular invasion, presence/absence of tunical invasion, percentage of each histological cell type present in the primary tumor. Immunohistochemical expression of MIB-1, p53, bcl-2, cathepsin D and e-cadherin was evaluated using a semiquantitative scoring ystem. Statistical analysis was performed by univariate and multivariate logistic regression models. Percentage of embryonal carcinoma [%EC (p < 0.001)] and presence of vascular invasion [VI (p < 0.0001)] were the most significant independent risk factors associated with pathological stage II disease. Combination of %EC and VI allowed correct prediction of final pathological stage in 88% of patients. Cut-off values including both variables identified correct pathological stage in 131/149 patients (88%). Less than 45% EC and absence of VI correctly identified pathological stage I disease in 91.5%; more than 80% EC and presence of VI correctly predicted pathological stage II in 88% of the patients. %EC and presence/absence of VI appear to be reliable prognosticators to identify both patients at high risk and at low risk for occult retroperitoneal disease. P53, bcl-2, MIB-1, cathepsin D and e-cadherin did not appear to be of prognostic value in clinical stage I NSGCT.
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PMID:[Histopathologic and biological prognostic factors of clinical stage I non-seminomatous germ cell tumors. Implications for risk-adjusted therapy]. 1023 39

Within the past 5 years, research has increasingly addressed molecular alterations in prostate cancer (CaP). Mutations of tumor suppressor gene p53 have been found in a variety of cancers, including urologic neoplasms. Several studies have been conducted on CaP specimens, citing frequencies of p53 alterations in localized cancers ranging from 4 to 60% and with more advanced hormone refractory disease, as high as 94%. The majority of studies have revealed a low percentage of p53 abnormalities in early-stage (clinically organ-confined) CaP. The overwhelming bulk of evidence suggests that the frequency of p53 abnormalities does increase with disease progression and is highest in tissues from patients with hormone-refractory prostate cancer. More recently, our group and others have found that focal p53 expression in the primary tumor by immunohistochemistry is predictive of cancer recurrence after radical prostatectomy. bcl-2 is an oncogene critically involved in the apoptosis, or programmed cell death. Overexpression of bcl-2 protein by immunohistochemistry has been commonly detected in advanced hormone refractory CaP. Our group recently has also shown that bcl-2 protein expression in primary CaP is a predictor of cancer recurrence after radical prostatectomy. Furthermore, the combination of p53 and bcl-2 protein expression were both independent predictors of recurrence after surgery. Most recently, we have shown that even though p53 and bcl-2 are predictive biomarkers when sampling the radical prostatectomy specimen, they are not useful to predict postoperative recurrence when sampling the pretreatment needle biopsy. Ki-67 is an antigen of cellular proliferation. Immunohistochemical staining for Ki-67 in archival material can be performed using the MIB-1 antibody. Unlike our results with p53 and bcl-2, Ki-67 protein expression by immunohistochemistry using MIB-1 was not an independent prognostic marker for cancer recurrence after radical prostatectomy although it may have clinical utility in subsets of patients. Assessment of MIB-1 staining in CaP needle biopsy samples is underway. Tumor neovascularity, or angiogenesis, is necessary for cancers to grow and metastasize. Angiogenesis in CaP as a prognostic marker has received recent attention. Most studies have used factor VIII immunohistochemical staining and increased angiogenesis has been suggested as a staging and prognostic marker. Our group has recently conducted a large study of radical prostatectomy patients and used CD34 antigen immunohistochemistry to assess neovascularity. We did not find that this biomarker assessment was an independent prognostic marker of cancer recurrence after radical prostatectomy. Further work is being conducted in needle biopsy samples. More research is needed to assess new biomarkers and, most importantly, to standardize the methodology for sampling and assaying biomarkers in heterogeneous and multifocal prostate cancer.
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PMID:Angiogenesis, p53, bcl-2 and Ki-67 in the progression of prostate cancer after radical prostatectomy. 1032 96

The protein MMP-2 (type IV collagenase) belongs to the family of metalloproteinases. Its function is related to cellular matrix degradation including basement membrane type IV collagen. Its presence in the neoplastic cells might enhance its capacity for dissemination. To find out some of its clinico-pathological and immunohistochemical behavior, 98 adenocarcinomas of the stomach were immunohistochemically studied, in search for MMP-2 in neoplastic cells. The results showed a correlation between MMP-2 with parietal depth of infiltration (p = 0.03) and with metastases in regional lymph nodes (p = 0.05). On the other hand, no correlation was found with sex, gastric localization, size of the tumor, histological type or grade neither with expression of MIB-1, c-erbB-2 nor p53 proteins, recurrence nor 5 year survival or no recurrency.
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PMID:[MMP-2 expression (type IV collagenase) in gastric cancer]. 1034 87

Fewer than 20 cases of primary pulmonary meningioma have been reported. Most of these cases have been histologically and clinically benign. We report an unusual case of primary pulmonary malignant meningioma with atypical histologic features and malignant behavior. A computed tomography scan of the head did not show evidence of tumor. The right upper lobe mass was resected and showed features of an atypical meningioma with loss of architectural pattern, mild nuclear pleomorphism, increased mitotic counts (up to 15 mitotic figures per 10 high power fields), and focally prominent nucleoli. Focally, cells with rhabdoid features were identified. The tumor's immunohistochemical and ultrastructural profiles were consistent with a meningioma. The tumor stained negative for estrogen and focally positive for progesterone receptors and had a MIB-1 labeling index (marker of cell proliferation) of 9.2%. Approximately 5 months after the initial resection, the patient experienced a tumor recurrence with multiple lymph node metastases, spread to the middle and lower lobes of the right lung, and metastasis to the diaphragm. Rarely, primary pulmonary meningiomas may present as high-grade malignant lesions.
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PMID:Primary pulmonary malignant meningioma. 1036 56

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

In a study based on formalin-fixed paraffin-embedded material from 86 patients with primary synovial sarcoma located in the extremities or on the trunk wall, the prognostic importance of MIB-1 index, p53-expession and tumour size was analysed. Multivariate analysis identified two metastatic risk factors: increasing tumour size and MIB-1 > 9%. The 5-year metastasis-free survival-rate for patients with tumour size < or = 5 cm + MIB-1 < 10% was 0.83 (95% confidence interval (CI) 0.64-0.92) compared to 0.31 (95% CI 0.11-0.53) in cases with tumour size > 5 cm + MIB-1 > or = 10%. Our study shows that metastatic disease in synovial sarcoma is closely related to MIB-1 index. Using our model based on tumour size and MIB-1 index, cases with good and poor prognosis can easily be discriminated. Therefore our model can be used to identify patients who should be considered for adjuvant chemotherapy.
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PMID:Ki-67 is strongly prognostic in synovial sarcoma: analysis based on 86 patients from the Scandinavian Sarcoma group register. 1046 1


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