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)

MIB-1 is useful in evaluating proliferative activity and in predicting the aggressiveness in a variety of tumors. To investigate if MIB-1 immunoreactivity can add prognostic information to conventional prognostic variables in papillary thyroid carcinoma (PTC), 30 PTCs were evaluated using the MIB-1 antibody. For comparison, 10 follicular thyroid carcinomas (FTC), 8 anaplastic thyroid carcinomas (ATC), and 96 follicular thyroid adenomas (FTA) were similarly analyzed. The median MIB-1 index was 0.5% in FTA, 1.9% in PTC, 2.7% in FTC, and 16.2% in ATC. The 13 tumors from patients classified as having aggressive PTC (defined as dead from disease, persisting disease, or the occurrence of distant metastases) had significantly higher MIB-1 index (median, 5.4%) than the 17 patients with nonaggressive disease (median, 1.1%). MIB-1 index 1.85% or more was found to be an independently significant risk factor for a less favorable clinical course in PTC. Because of overlap of single values the utility of MIB-1 index as a clinical test is somewhat limited. Still, at levels where no overlap occurs (MIB-1 index 2 3.2% or ' 0.5%) the index seems to add information to the established prognostic parameters. MIB-1 index should therefore be considered in routine histopathology of PTC.
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PMID:MIB-1 index in thyroid tumors: a predictor of the clinical course in papillary thyroid carcinoma. 1281 14

We report the clinicopathologic, immunophenotypic, DNA ploidy, and MIB-1 proliferative findings of five adenomatoid tumors of the adrenal gland. All patients were male, and tumors were incidental radiologic, surgical, or autopsy findings. Mean patient age at diagnosis was 41 years (range 31-64 years). The tumors ranged from 1.2 to 3.5 cm (mean 2.8 cm; median 3.2 cm) in greatest dimension, and all originated within the adrenal gland. The tumors were composed of anastomosing variably sized tubules lined by epithelioid as well as flattened cells. Signet-ring-like cells were present in all cases. The previously described histologic patterns of adenomatoid tumor, adenoid, angiomatoid, cystic, and solid, were observed, and each tumor contained multiple histologic patterns. In three of five cases, there was extra-adrenal extension of tumor into periadrenal adipose tissue. All adenomatoid tumors infiltrated the adrenal cortex, and in four cases the adrenal medulla was involved. All tumors exhibited strong immunoreactivity for calretinin, cytokeratins AE1/AE3, and CAM 5.2, cytokeratin 7, and vimentin. Tumors showed weak and focal immunoreactivity for cytokeratin 5/cytokeratin 6 and were negative for CD15, CD31, CD34, cytokeratin 20, MOC31, and polyclonal carcinoembryonic antigen. Ploidy analysis using Feulgen-stained sections and image analysis showed that three tumors were diploid and two were tetraploid. Tumors exhibited low MIB-1 proliferative activity, ranging from 0.2% to 2.7% (mean 1.6%). In three cases with clinical follow-up, no recurrence or metastases occurred. Adrenal gland adenomatoid tumors are morphologically and immunophenotypically identical to adenomatoid tumors of the genital tract and appear benign.
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PMID:Adenomatoid tumor of the adrenal gland: a clinicopathologic study of five cases and review of the literature. 1282 89

Florid von Brunn nests may mimic the nested variant of urothelial carcinoma. We examined formalin-fixed, paraffin-embedded tissue from 21 cases of florid von Brunn nests and 11 cases of nested variant of urothelial carcinoma. Morphologic features were recorded in detail. Also, cases were stained with monoclonal antibodies against MIB-1, p53, p27, and cytokeratin 20. Percentage positivity was calculated by counting 300 to 500 cells from each case. Clinical follow-up information was also obtained. Florid von Brunn nests from the bladder were comprised of large nests with regular spacing, and all the nests extended to the same horizontal level at the base of the proliferation. Central lumen formation was often seen within florid von Brunn nests, at times with cystic dilatation, such that there was a spectrum from proliferating von Brunn nests to cystitis glandularis to cystitis cystica. Small, crowded nests with variable spacing and an infiltrative base characterized nested variant of urothelial carcinoma. Four cases showed detrusor muscle invasion on biopsy with an additional case showing detrusor muscle invasion at cystectomy. One additional patient with nested variant of urothelial carcinoma had distant metastases and another had prostatic invasion. Nine of 21 florid von Brunn nests cases were from either the ureter or renal pelvis, whereas all cases of nested variant of urothelial carcinoma arose in the bladder. The ureteral and pelvic florid von Brunn nest cases showed smaller, more variable nests with irregular spacing closely mimicking nested variant of urothelial carcinoma but had a noninfiltrative base and often areas with either a lobular or linear array. Immunohistochemical studies showed nested variant of urothelial carcinoma to have higher MIB-1 expression (8.8% vs. 2.8%, P = 0.01). Nested variant of urothelial carcinoma had nonsignificantly higher p53 positivity (4.2% vs. 1.5%, P = 0.06) and lower p27 positivity (4.7% vs. 7.8%, P = 0.22). Cytokeratin 20 staining was not discriminatory. However, staining with each antibody was widely variable. Wide variation in staining for MIB-1, p53, p27, and cytokeratin 20 was seen in both florid von Brunn nests and nested variant of urothelial carcinoma, such that except for a few cases, a specific cutoff value could not be determined for diagnostic purposes. The findings underscore the importance of morphologic assessment in the distinction of florid von Brunn nests and nested variant of urothelial carcinoma.
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PMID:Florid von Brunn nests mimicking urothelial carcinoma: a morphologic and immunohistochemical comparison to the nested variant of urothelial carcinoma. 1296 Aug 9

The adhesion molecule E-cadherin has been shown to influence malignant transformation of tumors, including local and distant metastases. We examined the expression of E-cadherin to determine its relationship to the development of metastasis in metastatic brain tumors. Immunohistochemistry for E-cadherin and Ki-67 was carried out in 76 formalin-fixed, paraffin-embedded archival specimens of metastatic brain tumors and in 14 corresponding available primary tumors from patients who received treatment for metastatic brain tumors. The primary tumors were mainly lung cancers (51.3%), followed by gastrointestinal tumors (28.9%). E-cadherin was expressed in 62 (81.5%) of 76 cases examined. In metastatic adenocarcinomas, a consistent tendency for E-cadherin expression was noted, regardless of the degree of differentiation or the extent of spread of the disease (P = 0.04). There was a direct correlation between E-cadherin expression and high MIB-1 index in all metastatic brain tumors (P = 0.0007). Pairwise analysis in 14 primary tumors and the corresponding metastatic specimens revealed high E-cadherin and MIB-1 staining in metastatic brain tumors. These results provide a unique association between E-cadherin, systemic metastasis, and proliferation potential in metastatic brain tumors.
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PMID:Immunohistochemical expression of E-cadherin in metastatic brain tumors. 1460 26

Geriatric cancer patients present special challenges for clinicians. Few large series have been published in the last 20 years on the types of neoplasms that involve the central nervous system (CNS) in older individuals. To review types of neoplasms involving the central CNS that are currently being encountered by pathologists and neurosurgeons, we identified from our databases for the years 1992-2002, inclusive, patients 75 years or older who had symptomatic lesions requiring neurosurgical interventions. Retrospective characterization of tumors by immunohistochemistry, in situ hybridization, and fluorescence in situ hybridization was performed whenever possible and relevant to tumor type. Neurosurgical procedures (n=125) on 119 patients were identified; 90 patients were diagnosed as having neoplasms, with clot evacuation or infections being the most frequent non-neoplastic conditions necessitating surgery. Tumor types included glioblastomas (36 patients), meningiomas (16), pituitary adenomas (12), lymphomas or other hematological malignancies (8), anaplastic gliomas (5), metastases (6), head and neck malignancies with direct intracranial extension (3), and other miscellaneous tumor types (4). Compared with older literature series, we encountered a larger number of elderly patients with CNS lymphomas and fewer who came to surgery for CNS metastatic disease. In the "older old", glioblastomas are the most frequent symptomatic tumors necessitating surgical intervention. Glioblastomas in this aged cohort display the signature features of the small cell phenotype (62%), high cell cycle labeling indices (mean MIB-1-labeling index=25.1%), and either amplification of epidermal growth factor receptor or gain of chromosome 7 by fluorescence in situ hybridization (93% of assessable cases).
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PMID:Neoplasms involving the central nervous system in the older old. 1465 15

Nested variant of urothelial carcinoma is characterized by confluent small nests and abortive tubules of mildly atypical neoplastic cells infiltrating the lamina propria and/or muscularis propria of the bladder. Despite its deceptively bland histomorphologic appearance, the lesion is reported to have an aggressive behavior. The collective immunohistochemical expression of suppressor genes, growth factor, and proliferation activity marker has not been previously studied in this disease. Formalin-fixed, paraffin-embedded archival tissues from 12 cases of nested variant of urothelial carcinoma were stained with monoclonal antibodies to p21, p27, p53, EGF-R, and bcl-2, as well as the proliferation marker MIB-1. The area of predominant immunoreactivity was also evaluated. The pattern of immunostaining was compared with the clinical parameters. p21 was positive in 10 of 12 cases and located at the deepest portion of the tumor in 5 of 10 positive cases. Immunoreactivity for p27 was seen in 11 of 12 cases and limited to the superficial portion of the tumor in 9 of 11 positive cases. Only 3 and 2 of 12 cases were positive for p53 and bcl-2, respectively. MIB-1 immunoreactivity ranged from 2 to 35% of the neoplastic cells, with most tumors showing a proliferation index of >15%. Follow-up ranged from 3 to 30 months (mean, 17.6 mo). All patients except one were alive, although three patients developed metastases. Nested variant of urothelial carcinoma is a deceptively benign-appearing neoplasm with potential of deep invasion and metastases. Immunohistochemically, nested variant of urothelial carcinoma shares some features with high-risk conventional urothelial carcinomas, such as loss of p27 expression and high proliferation index. Nevertheless, p53, bcl-2, or EGF-r immunoreactivity is not frequently seen.
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PMID:Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 12 cases. 1468 30

Growth hormone-secreting pituitary adenoma is usually benign, and distant metastases are extremely rare. A case of growth hormone-secreting pituitary adenoma with multiple dural metastases is reported. A 53-year-old male was initially admitted to our hospital complaining of visual loss, presenting a pituitary abnormal mass with suprasellar extension. At the initial surgery, transsphenoidal surgery was selected, and the histological finding was benign pituitary adenoma. Seven and 16 months after the initial surgery, second and third surgeries via a transcranium route were performed for recurrence of the pituitary tumor. Histological findings revealed an appearance similar to the initial tumor in both surgical specimens. After the third operation, radiation therapy (local irradiation: total; 44 Gy) was performed. Six years after the first surgery, three tumors were located in the right frontal, parietal convexity and cerebellar tentorium. The tumors were totally removed by 4th and 5th surgeries. Histological examination showed malignant transformation from the primary benign growth hormone-secreting pituitary adenoma, with dural metastasis. Immunohistochemical staining with MIB-1 antibody demonstrated a high index of 7%. The patient is still alive after more than one year since the diagnosis of distant metastasis. According to previous reviews, few patients have survived more than one year. We conclude patients with benign pituitary adenoma should be carefully followed up for fear of malignant transformation or dural metastasis.
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PMID:[Intracranial metastasis of pituitary adenoma: a case report]. 1514 3

The natural course of pheochromocytomas (PCC) cannot be predicted for certain on the basis of primary histology, their malignant character can only be confirmed by the occurrence of metastases during follow-up. Based on the recently proposed PASS score for evaluation we examined 37 adrenal (36 sporadic and one familial) and six sporadic extra-adrenal paragangliomas (all designated as pheochromocytomas) with a 'malignant histology' to find additional predictive factors. Drawing upon the follow-up (18 months to 12 years, mean 5.8 years) metastasized (n=20) and nonmetastasized (n=23) courses could be distinguished. Metastasized PCC revealed significantly (P=0.03) more copy number changes on comparative genomic hybridization (CGH) (mean 8.3) than nonmetastasized tumors (mean: 4.3). The most frequent chromosomal alterations were losses on 1p (75.6%) and 3q (44%). Both were detected with identical frequency in metastasized and nonmetastasized PCC. A gain on 17q (P=0.025) was significantly predominant in malignant courses and suggests similarities in the genetic origin and progression of PCC and neuroblastomas. The proliferative activity (MIB-1 score) of metastasized PCC (n=20) was found to be significantly higher in metastasized tumors (mean 12.8% vs mean 3.5%). In contrast, the semiquantitatively scored membrane-bound staining of CD 44-S was stronger in tumors without metastases (mean 2.1 vs mean: 0.25) during the follow-up period (P<0.01). Although the results correspond to the established weight differences the tumor weight does not appear to be an independent prognostic factor. Our study suggests that CD 44-S and MIB-1 immunostaining as well as the CGH results might complement the PASS score in predicting a metastasized course of PCC. Regardless of tumor weight, tumors with a 'malignant histology' are highly prone to metastasize when more than 5% of MIB1-positive nuclei are present or CD44-S immunostaining is negative, or both. PCC with 10 or more copy number changes on CGH must be referred to as malignant tumors.
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PMID:CGH and CD 44/MIB-1 immunohistochemistry are helpful to distinguish metastasized from nonmetastasized sporadic pheochromocytomas. 1516 35

Survivin is a novel inhibitor of apoptosis. It is detected in fetal and neoplastic adult tissue, but not in normal tissues. Several recent studies have shown that survivin not only inhibits apoptosis, but also accelerates cancer cell proliferative activity. Expression of the protein may be of prognostic significance and therapeutic relevance in many cancers. We investigated survivin expression in hepatocellular carcinoma, correlating results with proliferation (MIB-1), prognostic factors, and outcome. Paraffin-embedded sections of 72 hepatocellular carcinoma were immunostained for survivin and MIB-1 using tissue microarray technology. Expression was evaluated in nuclei and cytoplasm as intensity (0-3+), and percentage of positive cells scored on a four-tiered system with less than 10%=negative; 10-25%=1; 26-50%=2; 51-75%=3; and 76-100%=4. Frequency of nuclear survivin expression was 43%. There was a significant correlation between nuclear survivin expression and nuclear grade (P=0.0271), microvascular invasion (P=0.0064), mitotic rate (P=0.0017), and MIB-1 (P=0.0001), as well as local recurrence (P=0.0487), and disease-free survival (P=0.0098). Histologic grade (P=0.0544) and stage (P=0.0548) tended to correlate with survivin expression, which did not correlate with cirrhosis, tumor necrosis, multiple tumors, metastatic disease, or overall survival. Survivin expression correlates with poor prognostic parameters (high nuclear and histologic grade, microvascular invasion, increased proliferation (mitotic count, MIB-1)), local recurrence, and shorter disease-free survival, but does not correlate with overall survival. An important role is suggested for survivin in progression, recurrence, and treatment of hepatocellular carcinoma.
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PMID:Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome. 1519 12

This paper reviews some aspects of the application of immunohistochemistry in gynaecological pathology. The use of cytokeratins 7 and 20 are discussed with reference to applications in ovarian pathology, including metastatic disease to the ovaries. Developments in utilising MIB-1 and p16 in cervical squamous and glandular lesions are discussed. Recent assertions regarding the differential diagnosis between endocervical and endometrial carcinomas are also reviewed. Antibodies that may be of use in the diagnosis of uterine mesenchymal and ovarian tumours are highlighted, as are antibodies of use in trophoblastic lesions including the use of p57 in evaluating hydatidiform moles.
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PMID:Immunohistochemistry in gynaecological pathology: a review. 1520 46


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