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)

Malignant mesothelioma (MM) is an uncommon tumor with high mortality and morbidity rates. It arises from mesothelial cells that line the pleural, pericardial, peritoneal, and testicular cavities. This is a disease with an indolent course because tumors arise 20 to 40 years after exposure to an inciting agent. Extensive research has shown that mesothelial cells are transformed into MM cells through various chromosomal and cellular pathway defects. These changes alter the normal cells' ability to survive, proliferate, and metastasize. This article discusses the alterations that occur in transforming normal mesothelial cells into MM. It also details some of the signal transduction pathways that seem to be important in MM with the potential for novel targeted therapeutics.
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PMID:Molecular biology of malignant mesothelioma: a review. 1632 20

The presence of effusion in a patient with a history of primary malignant tumor elsewhere in the body is generally accepted as a clinical manifestation of metastatic disease. Even in those cases, it is sometimes difficult to differentiate reactive mesothelial cells from carcinoma cells. Another challenging issue especially in the field of serous effusions is the differential diagnosis between malignant mesothelioma and metastatic adenocarcinoma. The aim of this study was to evaluate the potential use of the D2-40 antibody detecting the M2A oncofetal antigen in the diagnosis of malignant serous effusions. Two hundred and ninety effusion specimens (169 ovarian carcinomas, 44 breast carcinomas, 32 malignant mesotheliomas, 6 lung carcinomas, 8 reactive specimens, and 31 tumors of other origin) were assessed. Expression in reactive mesothelial cells was additionally assessed on 145 malignant effusions. Immunohistochemical analysis using the EnVision system was performed. M2A antigen was expressed in malignant mesotheliomas and reactive mesothelial cells in all specimens. Positive membranous staining was observed in 58% of ovarian carcinomas, 33% of lung carcinomas, and 30% of breast carcinomas. Pulmonary, breast, and nonovarian gynecologic tumors usually showed weak focal membranous staining, whereas the ovarian adenocarcinomas showed an expression pattern more similar to mesotheliomas. The results from the present study suggest low specificity for D2-40 as a mesothelial marker, especially in the context of differentiating mesothelial cells from ovarian carcinoma, and argue against its inclusion in the diagnostic panel of serous effusions.
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PMID:D2-40 is not a specific marker for cells of mesothelial origin in serous effusions. 1681 31

Spindle cell tumors that arise in or metastasize to the pleura must be thoroughly evaluated to arrive at a definitive diagnosis. Malignant mesothelioma is the most common tumor arising in the pleura, but metastatic tumors to the pleura occur more frequently. Additionally, many tumors arising in the lung and surrounding tissues involve the pleura. It is crucial to arrive at a correct diagnosis since many of these neoplasms show different prognoses and require varying treatment modalities. Sarcomatoid malignant mesothelioma is a rare tumor that arises in the pleura, and can be confused with numerous tumors arising in or metastasizing to the pleura, including synovial sarcoma, metastatic sarcomatoid carcinoma, metastatic melanoma, thymoma, renal cell carcinoma, localized fibrous tumor, leiomyosarcoma, and other types of sarcoma. Desmoplastic malignant mesothelioma is a fibrous sarcomatoid variant of malignant mesothelioma, and is occasionally mistaken for chronic fibrous pleurisy. Here, we review morphological, clinical, histological, immunohistochemical, ultrastructural, and molecular methods that aid in the diagnosis of spindle cell tumors of the pleura, and we provide specific examples of patients in which this multi-modal approach proved to be helpful.
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PMID:Spindle cell tumors of the pleura: differential diagnosis. 1704 95

Mesothelioma is a rare malignant neoplasm of the serosal membranes, which can give distant metastases in various organs in advanced stages of its course. Subcutaneous tissue is an unusual metastatic site. In the literature, only one case of metastatic mesothelioma to the skin of the face has been reported. We present a case of a 60-year-old female with a prior history of peritoneal malignant mesothelioma, who 6 months after the initial diagnosis presented with a subcutaneous nodule in the lateral chest wall. Cytological examination of the material obtained by FNA from the nodule revealed metastatic mesothelioma. Although subcutaneous metastasis of malignant mesothelioma is a rare entity, one must always keep this possibility in mind and proceed to further investigation of such lesions. In these cases, FNA is a simple diagnostic procedure for the identification of metastatic disease in patients with a prior history of malignancy.
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PMID:Subcutaneous metastasis of peritoneal mesothelioma diagnosed by fine-needle aspiration. 1718 90

Malignant mesothelioma is the most common primary pleural neoplasm. Angiogenesis is an important component of a variety of pathological processes, including carcinogenesis and tumor metastases. Vascular endothelial growth factor (VEGF) is the most potent known endothelial, cell specific mitogen. The authors assessed the relation between VEGF expression and clinicopathological variables or overall survival, in malignant mesothelioma. We studied 37 patients with malignant pleural mesothelioma and found that 36 out of 37 (97.3%) malignant mesothelioma samples were stained positively for VEGF. An increased expression of VEGF was observed in the epithelioid type compared with the other histological types of malignant mesothelioma, including the biphasic and sarcomatoid types. No statistically significant association was observed between VEGF expression and gender, age, or clinical stage. Furthermore, the expression of VEGF did not impact on the survival of patients with malignant mesothelioma. Although VEGF expression might be important for tumor development and maintenance, it was not identified as a prognostic factor in malignant mesothelioma.
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PMID:Expression of vascular endothelial growth factor in malignant mesothelioma. 1721 48

As the number of long-term cancer survivors increases, secondary malignancies are becoming a greater clinical issue. Although some of these malignancies may be related to common environmental exposures, a significant number are considered to be therapy-related. Pleural malignant mesothelioma is a neoplasm that may be related to asbestos exposure or radiation exposure. Previous reports of pleural mesothelioma as a second malignancy have tended to follow radiotherapy for extra-thoracic malignancies such as Hodgkin's disease, breast cancer and Wilms' tumor. We report the case of a 66-year-old woman with no prior asbestos exposure who developed pleural mesothelioma 17 years after pneumonectomy and adjuvant radiation therapy for non-small cell lung cancer. Opacification of the lung field from prior therapy made determination of the diagnosis more challenging. Secondary malignancies such as mesothelioma should be considered in patients who develop unexplained symptoms even long after treatment of a primary tumor.
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PMID:Malignant mesothelioma following thoracic radiotherapy for lung cancer. 1747 64

The increasing number of Malignant Mesothelioma (MM) cases that arrive for expert examinations to court for compensation reasons in subjects exposed to asbestos, in many instances rely exclusively on cytological smears of pleural effusion. We evaluated the accuracy and reproducibility of cytological pleural effusions, based on morphological criteria alone. Nine pathologists and eight residents from seven institutions in north-east Italy blindly examined 45 smears of MM (17), metastases (14) and benign effusions (14), in two rounds. Diagnoses had been confirmed by immunohistochemical and clinical follow-up, and eventually at autopsy. Diagnostic accuracy, interobserver and intraobserver agreement in the distinction of benign vs malignant cases, and in the differentiation of primary from metastatic malignancies, were evaluated. The distinction of benign from malignant smears resulted rather satisfactory (k=0.514), but markedly decreased in differentiation of MM from metastases (overall agreement: k=0.343), as well as when readings from residents were analyzed (k=0.132). Cytology is a useful and reliable tool in the identification of malignancies, but when the distinction of primary from metastatic tumors is addressed morphological criteria alone are not sufficient for a definite diagnosis of MM and the use of cell blocks, immunohistochemistry (IHC) and molecular ancillary techniques are recommended.
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PMID:Accuracy and reproducibility of pleural effusion cytology. 1770 24

Using gene expression arrays, we recently showed that MUC4 expression is significantly higher in ovarian/primary peritoneal serous carcinoma (OC/PPC) compared to diffuse peritoneal malignant mesothelioma (DMPM). In the present study, we analyzed the anatomic site-related expression of MUC4 in OC/PPC and studied its prognostic role. We additionally studied the ability of MUC4 to differentiate between OC/PPC and reactive mesothelial cells (RMC). OC/PPC effusions (n = 142) and benign reactive effusions (n = 10) were immunostained for MUC4 expression. Immunoreactivity was scored in carcinoma cells and RMC and was compared with tumor cell expression in 60 previously studied primary carcinomas and solid metastases and analyzed for association with clinicopathologic parameters, including survival. MUC4 was detected in carcinoma cells in 141/142 (99%) effusions, with comparable expression in peritoneal and pleural effusions. RMC were present in 72 malignant effusions and were MUC4-negative in all specimens, as well as in the 10 reactive effusions. MUC4 expression in carcinoma cells in effusions was significantly higher than in primary carcinomas and solid metastases (P < 0.001). Higher MUC4 expression was seen in tumors from older (>60 year) patients (P = 0.049). No association was found between MUC4 expression and other clinicopathologic parameters, including survival. MUC4 is universally expressed in OC/PPC effusions and is upregulated at this anatomic site compared to primary carcinomas and solid metastases. The data in the present study, together with our earlier report, show that MUC4 is an excellent marker for differentiating OC/PPC from both benign and malignant mesothelial cells.
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PMID:MUC4 is upregulated in ovarian carcinoma effusions and differentiates carcinoma cells from mesothelial cells. 1800 38

Patients with malignant pleural mesothelioma and negative N2 stage lymph nodes may benefit from extrapleural pneumonectomy with adjuvant therapy. The objective of this study is to describe the use of EUS-FNA to determine N2 stage status in patients with mesothelioma and its impact in the management of such patients. Six patients (mean age, 62 yr; median age, 63 yr; range, 52-70 yr; 5 men; 1 woman) underwent EUS-FNA for staging of N2 lymph nodes from July 2000 to July 2006. Follow-up included operative notes, treatment summaries, and surgical pathology. Eight sites were aspirated: four subcarinal lymph nodes, three aorto-pulmonary window lymph nodes, and one paraesophageal mass. Two of 8 (25%) aspirates were positive for metastatic disease in two different patients. Two false negative EUS-FNAs were observed and were attributed to sampling error not diagnostic error. No complications were observed. EUS-FNA is a safe N2 node staging technique in patients with mesothelioma. A positive N2 lymph node by EUS-FNA may be a contraindication to definitive surgery in patients with malignant mesothelioma.
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PMID:Endoscopic ultrasound-guided fine needle aspiration is useful for nodal staging in patients with pleural mesothelioma. 1806 85

The presence of cancer cells in effusions within the serosal (peritoneal, pleural, and pericardial) cavities is a clinical manifestation of advanced-stage cancer and is associated with poor survival. Tumor cells in effusions most frequently originate from primary carcinomas of the ovary, breast, and lung, and from malignant mesothelioma, a native tumor of this anatomic site. Unlike the majority of solid tumors, particularly at the primary site, cancer cells in effusions are not amenable to surgical removal and failure in their eradication is one of the main causes of treatment failure. In recent years, we have studied the biological characteristics of ovarian carcinoma, breast carcinoma, and malignant mesothelioma cells in effusions and compared it to their counterparts in primary tumors and solid metastases. Our data show that a large number of cancer-associated molecules, including cell adhesion proteins, proteolytic enzymes, growth factor receptors, signaling molecules, and transcription factors, are differentially expressed along tumor progression and have a different prognostic value, depending on the organ sampled. In ovarian carcinoma, several of these molecules are differentially expressed in primary diagnosis (prechemotherapy) and disease recurrence (postchemotherapy) specimens, reflecting the effect of disease progression and chemotherapy, and have different prognostic significance as function of disease progression. The findings presented in this review underscore the need to take into consideration the unique biology of cancer cells in effusions if patient-tailored molecular therapy is to become a successful treatment modality in these malignancies.
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PMID:Biological characteristics of cancers involving the serosal cavities. 1829 85


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