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)

We report here a case of ectopic pituitary adenoma with malignant transformation after repeated relapses. First, an ectopic pituitary adenoma producing follicle-stimulating hormone was found in the nasal cavity extending to the frontal cranial fossa. Despite repeated surgical resections of the tumor, it recurred three times in 2 years. The tumor gradually showed cellular atypia, mitosis, and necrosis. Immunohistochemical analyses revealed that the expressions of proliferating cell nuclear antigen and MIB-1 increased progressively. Moreover, the expression of p53 was detected at the second recurrence. Finally, at the third recurrence the tumor showed dissemination to the subarachnoid space and multiple metastases in the brain. The patient died of the tumor 10 months after the last resection. These findings indicate that the ectopic pituitary adenoma became malignant. To our knowledge, this is the first report on malignant transformation of ectopic pituitary adenoma. It is important to know that ectopic pituitary adenomas show malignant transformation and that the above parameters (proliferating cell nuclear antigen, MIB-1, and p53) may be useful indicators of the malignant potential of both ectopic and sellar pituitary tumors.
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PMID:Ectopic pituitary adenoma with malignant transformation. 1217 97

Few studies have examined the role of cell proliferation and apoptotic markers in chordomas. This study retrospectively reviews the clinicopathologic features of 26 chordomas and examines MIB-1, p53, bcl-2, and cyclin D1 immunoreactivity in these neoplasms. Patients ranged in age from 34 to 78 years (mean, 60.7 years) and included 14 females. The most common presentations included lower back pain (N = 15) and headaches (N = 10). Sixteen tumors arose in the lumbosacral region and 10 in the clivus. Initial surgery included biopsy (N = 17), subtotal resection (N = 4), and gross total resection (N = 5). The single highest mitosis count per 10 high power fields ranged from 0 to 6 (mean, 1). Marked nuclear pleomorphism was identified in seven tumors. Marked hypercellularity was seen in two tumors. Focal necrosis was identified in seven tumors. MIB-1 labeling indices (LI) in 22 tumors ranged from 0 to 3.8 (mean, 0.5). Cyclin D1 LI ranged from 0 to 82.4 (mean, 35.6). Seven tumors had positive p53 immunostaining and three demonstrated focal positive staining with bcl-2 antibody. Five tumors locally recurred; two patients developed metastatic disease. Thirteen patients received adjuvant chemotherapy and/or radiation therapy. At last known follow-up, seven patients died with tumor (12 to 132 months follow-up). Five additional patients died, two without tumor at 36 and 72 months follow-up and three patients in whom the tumor status at death was not known. Seven patients were alive with evidence of tumor (1 to 120 months) and five patients were alive without evidence of tumor (12 to 84 months). Clinical follow-up was not available in one patient. In conclusion, the low MIB-1 LIs and the lack of p53 and bcl-2 staining is in keeping with the low-grade nature of most chordomas. High cyclin D1 LIs may be reflective of a tendency to accumulate cyclin D1 protein; however, there appears to be a block in the effect of cyclin D1 on cell proliferation in these tumors. Cyclin D1, MIB-1, p53, and bcl-2 immunostaining does not appear to improve one's ability to predict behavior versus routine light microscopy.
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PMID:Apoptotic and proliferative markers in chordomas: a study of 26 tumors. 1217 Apr 53

Nodal nevi represent a potential diagnostic pitfall in the analysis of lymph nodes. They may be confused with metastatic melanoma or carcinoma. Although several morphologic guidelines exist for the recognition of nodal nevi, on occasion immunohistochemical studies may be helpful for diagnosis, especially when melanocytes extend into the lymph node parenchyma. To learn more about the immunohistochemical profile of nodal nevi we examined 15 nodal nevi for the expression of S-100 protein, gp100 (HMB-45), Melan-A/MART-1 (A103), and tyrosinase (T311), and we studied the expression of Ki-67 (MIB-1) in nodal nevi and 40 melanoma metastases (35 lymph node and five cutaneous metastases). All nodal nevi were homogeneously immunoreactive for S-100 protein, tyrosinase, and Melan-A/MART-1. Two nodal nevi were focally positive for gp100. Fourteen of 15 nodal nevi were completely negative for Ki-67. One large cellular nodal nevus showed nuclear labeling in <0.2% of melanocytes. All metastases showed MIB-1 labeling. However, the percentage of labeled tumor cells varied widely, ranging from 2% to 80%. These results demonstrate that MIB-1 and HMB-45 are helpful reagents for the distinction of nodal nevi from melanoma. Immunohistochemistry for S-100 protein, Melan-A/MART-1, or tyrosinase facilitates the recognition of melanocytes but does not distinguish between nodal nevus and metastatic melanoma.
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PMID:Expression of melanocyte differentiation antigens and ki-67 in nodal nevi and comparison of ki-67 expression with metastatic melanoma. 1236 50

It is important to identify T1-substage breast carcinomas (BCs) which are inherently aggressive, so that these can be managed more assertively. The purpose of this study was to distinguish those T1 BCs with the potential to metastasize to axillary lymph nodes from those lacking that ability by multiparametric analysis of several clinicopathologic features. The authors studied 197 patients with invasive BC who had undergone modified radical mastectomy; 161 tumors were ductal and 26 were lobular BCs. The study group was stratified by age into two groups: </=34 years (n = 34) and 35-84 years (n = 153). Pathologic lymph node status was correlated with estrogen receptor (ER) and progesterone receptor (PR) tumor positivity, MIB-1 proliferation index, and immunoreactivity for mutant p53 protein. These factors were studied immunohistologically using standard methodology and microwave-mediated epitope retrieval. Statistical analyses employed accepted techniques. Women in this study ranged from 22 to 84 years of age; 39 (21%) had positive lymph nodes. ER-positive tumors comprised 73% of the total; similarly, 65% were PR positive. The MIB-1 index was greater than 10% in 44% of lesions, and 14% demonstrated labeling for mutant p53 protein. Using crude odds ratio data, the MIB-1 index was the only indicator found to predict lymph node metastasis significantly (p < 0.001). Moreover, even when adjustments were made for patient age, logistic regression analysis confirmed the utility of MIB-1-values of greater than 10% in this context, with a 4.4 greater likelihood of metastasis (p < 0.001). MIB-1 indices of greater than 10% are associated with a risk of lymph node metastasis from T1 BCs, independent of patient age. Hormone receptor status and immunohistologic p53 status are not predictors of nodal involvement in this specific setting.
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PMID:Predictors of lymph node metastasis in T1 breast carcinoma, stratified by patient age. 1239 Mar 57

The current classification system of renal tumors is based on morphologic criteria, as supported by genetic findings. We present a group of previously unclassified tumors with similar morphologic and genetic features, suggesting a new entity within renal neoplasms. Seven renal tumors from five patients (ages 31-67 years) were analyzed. All cases were stained with periodic acid-Schiff, Hale's colloidal iron (HCI), and Alcian blue (AB) at pH 2.5/1.0 with and without hyaluronidase (HA) digestion. Immunohistochemical (IHC) stains were performed for CK8, CK18, CK19, vimentin, villin, Tamm-Horsfall protein (THP), renal cell carcinoma marker (RCC), epithelial membrane antigen (EMA), ulex europaeus agglutinin (UEA-1), soy bean agglutinin (SBA), peanut agglutinin (PNA), and MIB-1. Comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) studies were performed on all cases. All tumors showed circumscribed growth, a tubular growth pattern with focal solid areas, no significant nuclear atypia and absence of necrosis, desmoplasia, or inflammation. Abundant extracellular mucin was present. Immunohistochemistry stains support collecting duct origin (EMA+, PNA+, SBA+/-, CK 8/18/19+, vimentin+/-, UEA-1-, RCC-, villin-, THP-). The proliferative rate was low (<1%). CGH showed multiple consistent chromosomal losses (-1,-4, -6, -8, -9, -13, -14, -15, -22). Clinical outcome was favorable, with recurrences but no known distant metastases or death of disease. These findings are distinct from all previously classified renal neoplasms. Our data suggest the presence of a unique tumor entity within tumors of probable collecting duct origin: tubular-mucinous renal tumors of low malignant potential.
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PMID:Low-grade tubular-mucinous renal neoplasms: morphologic, immunohistochemical, and genetic features. 1242 95

Five cases of acral myxoinflammatory fibroblastic sarcoma that occurred in the distal extremities within the subcutaneous tissue are described. In one case, recurrence and metastases were recognized rather rapidly, only 3 months after the first excision. There have been no reports of early recurrence or metastases, especially the latter. The predominant type of constituent cells, cellularity of the neoplastic cells and density of inflammatory cells varied microscopically among cases. However, characteristic ganglion-like cells, Reed-Sternberg-like cells, round mononuclear cells and myxoid stroma, sometimes only seen focally, were found in all cases. Positive immunoreaction for vimentin was present in all cases. There was no correlation between positivity of MIB-1 or p53 for the primary tumor and presence of recurrence or metastases. In conclusion, we should be more cautious about the possibility of recurrence or metastases in earlier phases of acral myxoinflammatory fibroblastic sarcoma. Identification of the atypical bizarre fibroblastic component as the manifestation of the malignant nature of this lesion is vital to correct diagnosis, and it is important to attend to the myxoid and hyalinized zones, the inflammatory infiltrate, the presence of ganglion-like cells and acral location as features of acral myxoinflammatory fibroblastic sarcoma.
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PMID:Acral myxoinflammatory fibroblastic sarcoma: a report of five cases and review of the literature. 1253 11

Angiogenesis, which is the formation of new blood vessels from preexisting capillaries, plays an important role in tumor growth and metastasis. In this review, the focus is on angiogenesis in pituitary adenomas. Angiogenesis of pituitary adenomas has been assessed by studying tumor microvessel density using specific immunohistochemical markers to clarify the relationship between angiogenesis and tumor behavior. Unlike other organs, pituitary adenomas have significantly lower vascular densities as compared to nontumorous adenohypophysis, suggesting that the lack of significant angiogenesis may play a role in the slow pace of pituitary tumor growth and rarity of metastases. In addition, the relationship between microvessel density and various factors in pituitary adenomas is reviewed, including tumor types, age and sex, invasiveness, malignancy, several proliferative markers (MIB-1 or Ki-67). However, further studies will be needed, since many studies have reached opposite conclusions. Angiogenesis is a complex multistep process and several factors are found to be involved in each step of neovascularization, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and various other cytokines. VEGF and bFGF (or FGF-2), which are the most potent angiogenesis inducers among them, have been studied by immunohistochemistry, in situ hybridization, or in vitro studies in normal or adenomatous pituitaries and these results are also discussed in this review.
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PMID:Angiogenesis in pituitary adenomas. 1253 78

Histologically confirmed local recurrence of the rare entity of a granular cell tumor of the vulva was diagnosed in a 55-year-old patient with no signs of distant metastasis. Intraoperatively (local excision of mons pubis and inguinal lymphnodes), widespread regional metastasis with retroperitoneal lymphnode metastases were found. Postoperative restaging detected pulmonary, hepatic and skeletal metastases and the patient died of her disseminated disease within 4 months. Early diagnosis of the malignant phenotype of granular cell tumor using expression of S-100-protein, MIB-1, vimentin and p53 is suggested. Once a malignant granular cell tumor is diagnosed histologically, thorough staging procedure should be performed to exclude disseminated disease. If this is the case, radical surgery should be tried due to the lack of efficiency of radiotherapy and of systemic treatments.
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PMID:Recurrence and rapid metastasis formation of a granular cell tumor of the vulva. 1255 96

The clinical and histopathological distinction between benign and malignant pheochromocytomas and paragangliomas is difficult, and reliable diagnostic markers are lacking. Here we have evaluated the prognostic value of human telomerase reverse transcriptase (hTERT) gene expression detected by reverse transcription PCR (RT-PCR); telomerase activity (TA) measured by TRAP (telomeric repeat amplification protocol) assay; immunohistochemical staining for Ki-67/MIB-1; and the mRNA expression of matrix metalloproteinase (MMP)-2 and EMMPRIN (extracellular matrix metalloproteinase inducer) analyzed by in situ hybridization in 32 primary pheochromocytomas or abdominal paragangliomas. hTERT was expressed in 7/11 malignant tumors (defined as presence of metastasis and/or extensive local invasion) as compared with in 2/21 benign tumors. All of the benign tumors showed <1% proliferative activity, as measured by Ki-67/MIB-1 staining. In all three patients with malignant tumors who developed metastases and/or invasive local recurrence during follow-up, the tumors were positive for either hTERT expression or Ki-67/MIB-1 immunoreactivity. TA was not a significant discriminator between benign and malignant tumors, and the value of EMMPRIN and MMP-2 as predictive markers was limited. In conclusion, the findings imply that the combined use of Ki-67/MIB-1 and hTERT, in addition to histopathology, provides a highly specific tool to identify benign pheochromocytoma and abdominal paraganglioma cases that are not at risk of developing recurrent or metastatic disease.
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PMID:KI-67 AND hTERT expression can aid in the distinction between malignant and benign pheochromocytoma and paraganglioma. 1264 Jan 5

We report five silent corticotroph carcinomas of the pituitary gland. They represent 0.05% of adenohypophyseal tumors surgically treated at Mayo Clinic during a 20-year period and about 5% of all reported pituitary carcinomas. The patients (three females and two males), ranging in age from 26 to 58 years (mean 39 years, median 35 years) presented with symptoms of mass effect; none had Cushing's disease. All tumors were initially invasive macroadenomas, recurred locally, and metastasized, three outside the central nervous system. The follow-up period ranged from 2 to 23 years (mean 10.6 years). All patients died, four of disseminated tumor and one of myocardial infarction. Histologically, three of the primary lesions were indistinguishable from an ordinary benign adenoma. Two were initially diagnosed as atypical adenomas as they featured nuclear pleomorphism, prominent nucleoli, mitotic activity, high MIB-1 labeling indices, and p53 overexpression. For the purpose of comparison, 17 silent corticotroph adenomas were also investigated. In addition, the clinicopathologic features of the silent carcinomas were compared with those of a meta-analysis of published Cushing's disease-associated pituitary carcinomas. The silent adrenocorticotropin carcinomas showed a propensity for extraneural dissemination and an outcome similar to those of the Cushing's disease-associated carcinomas. The two patients with initial atypical tumors died with metastases outside the central nervous system at 2 and 4 years, whereas the three patients with tumors lacking atypia died 16, 18, and 23 years after initial sellar surgery.
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PMID:Silent corticotroph carcinoma of the adenohypophysis: a report of five cases. 1265 32


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