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Malignant Mesothelioma (malignant + mesothelioma)

Distribution by Scientific Domains

Medical Sciences	96%

Distribution within Medical Sciences

Pathology	63%
Oncology & Radiotherapy	16%

Selected Abstracts

Mesothelioma in a worker who spun chrysotile asbestos at home during childhood

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 4 2009
Eiji Yano MD
Abstract Background Malignant mesothelioma has a long latency period and more commonly found in those exposed to amphibole than chrysotile asbestos. Method A 35 years old asbestos worker in an asbestos textile plant in Chongqing, China, developed mesothelioma after only 4 years of employment. He was born and bred in a company residence of an asbestos plant and manually spun asbestos thread during school age. In the plant, not amphibole but only chrysotile has been used. Results Diagnosis of malignant mesothelioma was confirmed by comprehensive approaches including gross appearance, histology, histochemistry, and immunocytochemistry. In the lung and tumor tissues, huge number of tremolite with exceptional chrysotile was observed despite the reverse proportion in the work environment. Discussion Residential exposure and home spinning of asbestos seemed contributed to the early development of mesothelioma in this subject. Although only chrysotile was used and contamination of tremolite was low in the work environment, chrysotile seemed to be cleared leaving tremolite remain in the tissue. Conclusion Chrysotile with little contamination of tremolite can lead to early development of malignant mesothelioma when heavily exposed from childhood at a company residence with household exposure. There can be several mechanisms for tremolite to remain in the lung tissue, far exceeding chrysotile in number. Am. J. Ind. Med. 52:282,287, 2009. © 2009 Wiley-Liss, Inc. [source]

Mesothelioma in blood related subjects: Report of 11 clusters among 1954 Italy cases and review of the literature

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 5 2007
Valeria Ascoli
Abstract Background Malignant mesothelioma is a sporadic tumor related to asbestos. Its occurrence in blood relatives raises the question of potential contribution of predisposing factors. Methods The study analyses the features of mesothelioma in blood relatives that might explain the disease clustering. Data sources of familial clusters were three population-based Mesothelioma Registries in Italy (Veneto and Apulia Regions, Brescia province; 1978,2005) and Medline, Toxline, and Oshline/Hseline databases for a review of the literature (1968,2006). Results Eleven clusters (22 cases) were identified among 1954 Italy mesothelioma cases, and 51 clusters (120 cases) were extracted from 33 studies. The proportion of Italy familial cases was 1.4 per 100 mesothelioma cases; the ratio between the number of familial clusters and the number of non-familial mesothelioma cases was 1:148. The mesothelioma profile in consanguineous is the same as in non-consanguineous subjects (male prevalence; pleural site; age at diagnosis >50 years; asbestos exposure). Most clusters occurred in asbestos workers (shipyard, asbestos-cement production/processing, and insulation) and household-exposed blood relatives. Others were related to asbestos-cement factory pollution, asbestos-in-place, and handling asbestos-contaminated textiles. Two clusters were without any known exposure. Cancer family history revealed lung cancer cases in eight clusters. Conclusions Available data support asbestos exposure as the main risk factor in mesothelioma cases among blood relatives. Our finding of a low proportion of familial cases would not suggest the influence of a large genetic component for mesothelioma in blood relatives. Am. J. Ind. Med. 50:357,369, 2007. © 2007 Wiley-Liss, Inc. [source]

Malignant mesothelioma in Australia, 1945,2000,

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 3 2002
James Leigh MB
Abstract Background Australia has maintained a total national malignant mesothelioma case register since 1980. There has been a marked increase in the incidence of mesothelioma in the last 20 years. Currently 450,600 cases are notified annually in a population of 20 million. While the history of the Wittenoom (Western Australia) crocidolite mine and its aftermath is well known, these cases comprise only 5% of the total. This study describes the incidence of mesothelioma in Australia from 1945 to 2000. Methods Using register data, time trends in mesothelioma incidence were calculated. Analyses of incidence are reported by age, sex, anatomical site, and state of notification. Associations with occupational and environmental asbestos exposure histories are described. Lung fiber content measurements were made on a subset of cases. Results Australia has had 6,329 cases of mesothelioma from 1 January 1945 to 31 December 2000. (A further 620 cases were notified in the period from 1 January 2001 to 31 October 2001.) Annual incidence rates for Australia per million population ,,20 years (1997) were: male, 59.8; female, 10.9; total, 35.4. Incidence rates have been continually increasing and are the highest reported national rates in the world. While Western Australia has the highest rate (1997 total rate, 52.8), most cases arise from the two most populous eastern states, New South Wales and Victoria. In 88% (male 90%, female 61%) of cases, a history of asbestos exposure was obtained. Exposures occurred in a wide variety of occupational and environmental circumstances. In 80% of cases with no history of exposure, TEM lung asbestos fiber counts >,200,000 fibers >,2 ,m length per gm dry lung were obtained, suggesting unrecognized exposure. Conclusions Australia's high incidence of mesothelioma is related to high past asbestos use, of all fiber types, in a wide variety of occupational and environmental settings. The number of cases in total is expected to be about 18,000 by 2020, with about 11,000 yet to appear. Am. J. Ind. Med. 41:188,201, 2002. © 2002 Wiley-Liss, Inc. [source]

Molecular characterization of tumour heterogeneity and malignant mesothelioma cell differentiation by gene profiling

THE JOURNAL OF PATHOLOGY, Issue 1 2005
Xiaojuan Sun
Abstract Malignant mesothelioma is an aggressive tumour, characterized by a variable differentiation pattern and poor prognosis. At present, the clinical outcome in patients with malignant mesothelioma is mainly predicted by the morphological phenotype of the tumour. However, this conventional clinicopathological parameter is of limited value, partly because of the biological heterogeneity of this tumour and poor understanding of the regulatory mechanisms underlying the various patterns of growth. To elucidate the intrinsic molecular programmes that determine tumour differentiation, oligonucleotide arrays were used in an in vitro model of mesothelioma differentiation. The analysis of 2059 genes detected 102 genes that were significantly deregulated. Clustering of these genes into functional categories showed distinctive patterns for the two phenotypes, namely epithelioid and sarcomatoid. The molecular fingerprint of the sarcomatoid tumour component indicates overrepresentation of growth factor receptors and growth factor binding proteins, whereas epithelioid mesothelioma cells express other tumour-promoting factors involved in differentiation, metabolism, and regulation of apoptosis. These differences in the molecular phenotype may give a better basis for diagnosis and for designing novel therapies. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Genomic abnormalities and signal transduction dysregulation in malignant mesothelioma cells

CANCER SCIENCE, Issue 1 2010
Yoshitaka Sekido
Malignant mesothelioma (MM) is a tumor with poor prognosis associated with asbestos exposure. While it remains to be clarified how asbestos fibers confer genetic/epigenetic alterations and induce cellular transformation in normal mesothelial cells, the understanding of key molecular mechanisms of MM cell development, proliferation, and invasion has progressed. MM shows frequent genetic inactivation of tumor suppressor genes of p16INK4a/p14ARF and neurofibromatosis type 2 (NF2) which encodes Merlin, and epigenetic inactivation of RASSF1A. However, no frequent mutations of well-known oncogenes such as K-RAS and PIK3CA have been identified. Activation of multiple receptor tyrosine kinases including the epidermal growth factor receptor (EGFR) family and MET, and subsequent deregulations of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K),AKT signaling cascades are frequently observed in most MM cells. The tumor suppressive function of Merlin in MM cells is also being investigated by dissecting its possible downstream signaling cascade called the Hippo pathway. Further comprehensive delineation of dysregulated signaling cascades in MM cells will lead to identification of key addiction pathways for cell survival and proliferation of MM cells, which strongly promote establishment of a new molecular target therapy for MM. (Cancer Sci 2009) [source]

3- O -Methylfunicone, a metabolite produced by Penicillium pinophilum, modulates ERK1/2 activity, affecting cell motility of human mesothelioma cells

CELL PROLIFERATION, Issue 2 2010
E. Buommino
Objectives:, 3- O -methylfunicone (OMF), a secondary metabolite produced by Penicillium pinophilum, affects cell proliferation and motility in a variety of human solid tumours. The aim of this study was to demonstrate whether OMF has the ability to arrest cell division and motility, in a human mesothelioma cell line. Malignant mesothelioma is an aggressive cancer that does not respond to standard therapies the cells of which are considered to be highly resistant to apoptosis. Material and methods:, Cell motility and invasion were measured using a modified Boyden chamber. Gene expression was examined by RT-PCR, while ERK1/2 was investigated by Western blot analysis. All experiments were also performed on primary cultures of mesothelial cells. Results:, The present study shows that OMF inhibited motility of the NCI mesothelioma cell line by modulating ERK signalling activity, and affected ,V,5 integrin and MMP-2 expression, inducing marked downregulation at both mRNA and protein levels. Substantial downregulation of VEGF gene expression was also demonstrated. These effects were not observed in normal mesothelial cell cultures. Conclusion:, OMF may have potential as a naturally derived anti-tumour drug for treatment of mesothelioma. [source]

Mesothelioma Symposium 11.30,12.30 Tuesday 16 September 2003

CYTOPATHOLOGY, Issue 2003
Darrel Whitaker Dr
The diagnosis of malignant mesothelioma on the cytology of serous effusions is a two-phase process. First is to determine that the effusion is malignant based on morphological features such as a highly cellular fluid with many large three dimensional cell aggregates, and/or the recognition of minor malignant criteria including prominent cell engulfment, uniformly present very prominent nucleoli, or the finding of very large (giant) cells. In cell block sections, strong positive staining with EMA often with cell membrane accentuation provides compelling support for a cytological diagnosis of malignancy. Second is to recognize that the malignant cells have a mesothelial phenotype and do not represent metastatic malignancy (usually adenocarcinoma). Criteria in support of mesothelioma include the lack of a ,two cell' population, that is one native (mesothelial) and one foreign (metastatic), cells with abundant dense staining cytoplasm, the presence of ,windows' where mesothelioma cells lie in close apposition and intracytoplasmic glycogen presenting either as small peripheral vacuoles on MGG stained smears or large yellow refractile crescents on Papanicolaou stained smears. In addition, mesothliomas often possess connective tissue stromal cores occurring as either well-formed collagen within papillary aggregates or lying free as pink (MGG) or light green (Pap) amorphous material in the background of the smear or in loose association with mesothelioma cells. Finally small orange staining squamous-like cells can occasionally be identified and sometimes this may be a very prominent finding and has resulted in the false impression of a squamous cell carcinoma. Almost certainly these cells represent apoptotic tumour cells. The connective tissue mucin hyaluronic acid may be found as a net-like pattern in the smear background or as large hard-edged magenta-stained vacuoles on MGG-stained smears. Cell block sections provide architectural information and it is usually possible to separate mesothelioma aggregates with their cuboidal cells, central nuclei and abundant dense cytoplasm arranged in solid, papillary or hollow clusters from those of adenocarcinoma with less dense, often foamy cytoplasm, often composed of columnar cells with elongated nuclei. Aggregate form in adenocarcinoma can be variable but true acini are a rare finding. These cell block sections provide an ideal medium for histochemistry (PAS with and without diastase digestion) and immunocytochemistry. By using a panel of antibodies (Calretinin and CK 5/6, BerEp4, CEA, B72.3) it is almost always possible to distinguish mesothelioma from metastatic adenocarcinoma. Calretinin and CK 5/6 positive staining and absent staining with BerEp4, CEA and B72.3 is considered diagnostic of mesothelioma. [source]

Invited review The cytology of malignant mesothelioma

CYTOPATHOLOGY, Issue 3 2000
D. Whitaker
[source]

Evidence-based guidelines to optimize the selection of antibody panels in cytopathology: Pleural effusions with malignant epithelioid cells

DIAGNOSTIC CYTOPATHOLOGY, Issue 1 2010
Danielle E. Westfall M.D.
Abstract There is no established methodology to help select cost effective antibody panels. We used Bayesian statistics and an evidence-based pathology (EBP) approach to retrospectively review the use of immunohistochemistry (IHC) in 153 consecutive pleural effusions evaluated in our laboratory from 2005,2007 for the differential diagnosis of malignant mesothelial cells versus carcinoma cells and to estimate the likely site of origin of a carcinoma. The results in this "training" set were used to design antibody panels and test their clinical applicability on a "test set" of 44 pleural effusions collected in early 2008. Cytopathologists had used 6 ± 4.5 IHC tests per case for the diagnosis of malignant mesothelioma (n = 9) and carcinomas of lung (n = 60), breast (n = 47), Müllerian (n = 25), and other origins in the "training set". The sensitivity and specificity of pleural cytology using all these IHC tests were 32% and 95%, respectively. Sensitivity, specificity and post-test odds (PTO) of a positive IHC result were calculated for each antibody and by the following classes: malignant mesothelial cells and carcinoma cells by primary site of origin. The antibodies that provided the best PTO to diagnose the most prevalent tumors in our population were included in diagnostic panels for male (calretinin, TTF-1, PSA and CDX-2) and female (calretinin, TTF-1, ER and CA125) patients. These panels provided 100% specificity and 77% and 50% sensitivity, respectively, for the pleural effusions from female and male patients in the "test set." The use of an EBP approach for test selection in cytopathology is discussed. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source]

Effusion cytomorphology and immunocytochemistry of malignant melanoma: Five cases of melanotic melanoma and one case of amelanotic melanoma

DIAGNOSTIC CYTOPATHOLOGY, Issue 7 2009
I.A.C., Katsuhide Ikeda C.T.
Abstract Effusion cytological analyses of amelanotic malignant melanoma (AMM) are very rare and no concise description of AMM related cytomorphologic features using effusion have been reported. Here, we report the cytomorphological, immunohistochemical, and immunocytochemical findings in the effusion cytology of six cases of malignant melanoma (MM), one case of AMM, and five cases of melanotic malignant melanoma. Papanicolaou-stained smears exhibited conspicuous nucleoli, multinucleation, and cytoplasmic vacuolization in all of the MM cases. In addition, the AMM case displayed numerous mitotic figures and intranuclear cytoplasmic inclusions. With regard to the immunohistochemistry findings, all six cases of melanoma were positive for Melan-A/MART-1, HBME-1, and S-100. In the immunohistochemistry analyses, five of six cases of melanoma were positive for WT-1, as was the AMM specimen. Furthermore, because the effusion analysis of malignant mesothelioma proved positive for WT-1, it should be noted that WT-1 effusion analysis is not an appropriate means to distinguish between MM and malignant mesothelioma. We suggest that it is important to recognize cytomorphologic characteristics, such as melanin pigment, conspicuous nucleoli, multinucleation, and cytoplasmic vacuolization, and to choose appropriate antibodies for the correct diagnosis of MM in effusion. Diagn. Cytopathol., 2009. © 2009 Wiley-Liss, Inc. [source]

Cytopathologic differential diagnosis of malignant mesothelioma, adenocarcinoma and reactive mesothelial cells: A logistic regression analysis,

DIAGNOSTIC CYTOPATHOLOGY, Issue 1 2009
Ebru Cakir M.D.
Abstract Distinguishing malignant mesothelioma, adenocarcinoma and reactive mesothelial proliferation in both cytologic and surgical pathologic specimens is often a diagnostic challenge. Conventional cytomorphologic assessment is an important step in the differential diagnosis of these entities. The pleural effusion cytologies from 40 cases of malignant mesothelioma, 40 cases of adenocarcinoma and 30 cases of reactive mesothelial proliferation diagnosed between 1997 and 2007 were reviewed. Twenty-seven cytologic features which are regarded as useful in the differential diagnosis of mesothelioma, adenocarcinoma and benign mesothelial proliferation were assessed. These cytologic features were subjected to a stepwise logistic regression analysis. Three features were selected to distinguish malignant mesothelioma from adenocarcinoma: giant atypical mesothelial cell (P = 0.0001), nuclear pleomorphism (P = 0.0001) and acinar structures (P = 0.0001), the latter two being characteristics of adenocarcinoma. The variables selected to differentiate malignant mesothelioma from reactive mesothelial cells were: cell ball formation (P = 0.0001), cell in cell engulfment (P = 0.0001) and monolayer cell groups (P = 0.0001), the latter being a feature of benign mesothelial proliferation. When these selected variables were subjected to a stepwise logistic regression analysis, the logistic model correctly predicted 90% of cases of benign mesothelial proliferation versus 97.5% of malignant mesothelioma and 92.5% of malignant mesothelioma versus 92.5% of adenocarcinoma. Conventional cytomorphologic assessment is the first step to establish an accurate diagnosis in pleural effusions. Several cytologic features have predictive value to seperate malignant mesothelioma from adenocarcinoma and reactive mesothelial proliferation. Diagn. Cytopathol. 2009. © 2008 Wiley-Liss, Inc. [source]

MUC4 is upregulated in ovarian carcinoma effusions and differentiates carcinoma cells from mesothelial cells

DIAGNOSTIC CYTOPATHOLOGY, Issue 12 2007
Ben Davidson M.D., Ph.D.
Abstract 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. Diagn. Cytopathol. 2007;35:756,760. © 2007 Wiley-Liss, Inc. [source]

Kallikrein 4 is expressed in malignant mesothelioma,Further evidence for the histogenetic link between mesothelial and epithelial cells

DIAGNOSTIC CYTOPATHOLOGY, Issue 2 2007
Ben Davidson M.D., Ph.D.
Abstract The objective of this study was to analyze Kallikrein 4 protein (hK4) expression in effusions and solid tumors of patients diagnosed with malignant mesothelioma (MM) and compare hK4 expression in MM with that in breast and ovarian adenocarcinomas. Sections from 65 MM (21 effusions, 44 solid tumors) and 63 breast carcinomas (28 effusions, 35 solid tumors) were stained for hK4 using immunohistochemistry. Results were compared with our previously published data for 284 ovarian carcinomas (181 effusions, 103 solid tumors). Expression of hK4 was detected in 26/65 (40%) MM and 52/63 (83%) breast carcinomas. Ovarian carcinoma showed staining values that were comparable to those in breast carcinoma (expression of hK4 in 144/181; 80% effusions and 85/103; 83% solid tumors). As opposed to our previous findings in ovarian carcinoma, hK4 expression was higher in solid tumors when compared with to effusions in both MM (P = 0.013) and breast carcinoma (P = 0.002). Comparative analysis of the three tumor types showed significantly higher expression in ovarian and breast adenocarcinomas when compared with MM (P < 0.001). In conclusion, hK4 is frequently expressed in MM, with higher levels detected in solid tumors, although its expression is more limited than in gynecological adenocarcinomas. The presence of hK4 in MM, a non-hormonally regulated tumor, provides further support to the histogenetic link between mesothelial and epithelial cells. Diagn. Cytopathol. 2007;35:80,84. © 2007 Wiley-Liss, Inc. [source]

The diagnostic utility of D2-40 for malignant mesothelioma versus pulmonary carcinoma with pleural involvement

DIAGNOSTIC CYTOPATHOLOGY, Issue 12 2006
Ph.D., Reda S. Saad M.D.
Abstract Differentiating malignant mesothelioma (MM) from pulmonary carcinoma in pleural fluid cytology can be challenging. Recent studies have suggested that D2-40, a novel lymphatic marker, may be a useful marker for mesothelial differentiation in surgical specimens. However, there are no available data regarding its utility in effusion cytology specimens. We investigated the utility of D2-40 in pleural fluid cytology in differentiating MM from pulmonary carcinomas. Twenty cases of pleural effusion smears of surgically confirmed MM with their corresponding cell blocks were retrieved from the database of the hospital computer system. We also included 10 cases of metastatic pulmonary adenocarcinoma (PA) and 10 cases metastatic pulmonary squamous cell carcinoma (PSCC) involving the pleural fluid. Cell blocks were formalin-fixed, paraffin embedded, and immunostained for TTF1, p63, calretinin, CK5/6, WT-1, and D2-40. Cases were scored as negative (<5% positivity) or positive (>5% moderate/strong positivity). The positive rates for TTF1, p63, calretinin, CK5/6, WT-1, and D2-40 were as follows: MM (0/20), (0/20), (17/20), (18/20), (19/20), (17/20), for PA (8/10), (0/10), (3/10), (0/10), (0/10), (0/10), and for PSCC (1/10), (10/10), (6/10), (10/10), (0/15), (0/10). The staining pattern for D2-40 was characterized by thick membranous staining. Diffuse cytoplasmic staining by D2-40 was seen in 2 cases of pulmonary carcinoma, counted as negative. Our study showed that in differentiating MM from PA, CK5/6, WT-1, and D2-40 have high specificity and sensitivity for MM. Although calretinin is a sensitive IHC marker for MM, it is not specific since it stained 30% of PA. Conversely, to differentiate between MM and PSCC, p63 and WT-1 are the best available markers. We recommend a panel of CK5/6, p63, D2-40, and WT-1 to differentiate MM from pulmonary carcinomas in effusion cytology specimens. Diagn. Cytopathol. 2006; 34:801,806. © 2006 Wiley-Liss, Inc. [source]

The use of the monoclonal antibody mesothelin in the diagnosis of malignant mesothelioma in pleural biopsies

HISTOPATHOLOGY, Issue 6 2006
Article first published online: 20 APR 200
No abstract is available for this article. [source]

Sister Mary Joseph's nodule in malignant mesothelioma

HISTOPATHOLOGY, Issue 3 2004
M K Heatley
No abstract is available for this article. [source]

Cytokeratin 14 expression in epithelial neoplasms: a survey of 435 cases with emphasis on its value in differentiating squamous cell carcinomas from other epithelial tumours

HISTOPATHOLOGY, Issue 1 2001
P G Chu
Cytokeratin 14 expression in epithelial neoplasms: a survey of 435 cases with emphasis on its value in differentiating squamous cell carcinomas from other epithelial tumours Aims:,The tissue distribution of cytokeratin 14 (CK14) in epithelial neoplasms is not well defined. We have evaluated 435 cases of epithelial neoplasm of various origins with cytokeratin 14 monoclonal antibody with special attention to possible use in differential diagnosis. Methods and results:,Immunohistochemistry (ABC,HRP method) was performed for detection of CK14. We found that the expression of cytokeratin 14 was generally restricted to: (i) the majority of cases of squamous cell carcinoma regardless of origin (67/74) and degree of differentiation; (ii) neoplasms with focal squamous differentiation, including endometrial, and ovarian adenocarcinoma, malignant mesothelioma and transitional cell carcinoma; (iii) thymoma (8/8); (iv) myoepithelial components of salivary gland pleomorphic adenoma (3/4); and (v) oncocytic neoplasms, including thyroid Hurthle cell adenoma (1/1) and salivary gland Warthin's tumour (2/2). Conclusion:,CK14 protein is a useful marker in differential diagnosis of squamous cell carcinomas. [source]

Immunohistochemistry and the diagnosis of malignant mesothelioma

HISTOPATHOLOGY, Issue 5 2001
J E King
[source]

Aberrant promoter methylation of insulin-like growth factor binding protein-3 gene in human cancers

INTERNATIONAL JOURNAL OF CANCER, Issue 3 2007
Kunitoshi Tomii
Abstract Insulin-like growth factor binding protein-3 (IGFBP-3) is postulated to be a mediator of growth suppression signals. Here, we examined the methylation status of IGFBP-3 to correlate to clinicopathological factors in human cancers. The methylation status of IGFBP-3 was determined by bisulfite DNA sequencing and was correlated with expression semi-quantified by real-time RT-PCR to develop a methylation-specific PCR (MSP) assay for IGFBP-3. Using the MSP assay, we examined the methylation status of IGFBP-3 in gastric cancer (GC), colorectal cancer (CRC), breast cancer (BC) and malignant mesothelioma (MM). IGFBP-3 methylation was detected in 6 of 13 (46%) and 16 of 24 (67%) GC cell lines and tumors, respectively; 4 of 8 (50%) and 15 of 26 (58%) CRC cell lines and tumors, respectively; 3 of 11 (27%) and 7 of 39 (18%) BC cell lines and tumors, respectively and 1 of 5 (20%) and 18 of 56 (32%) MM cell lines and tumors, respectively. Interestingly, the methylation status of MM specimens from Japanese patients (75%, 12 out of 16 patients) was significantly higher than those from the USA (15%, 6 out of 40 patients) (p < 0.0001), suggesting the presence of ethnic differences in the IGFBP-3 methylation status. We also found that IGFBP-3 methylation was preferentially present in GCs arising in the lower-third of the stomach (p = 0.079). In summary, our results showed that IGFBP-3 methylation played an important role in the silencing of its expression, suggesting that IGFBP-3 may act as a tumor suppressor gene in several human cancers examined. © 2006 Wiley-Liss, Inc. [source]

Peritoneal mesothelioma presenting as an acute surgical abdomen due to jejunal perforation

JOURNAL OF DIGESTIVE DISEASES, Issue 4 2007
Nikolaos S SALEMIS
BACKGROUND: Peritoneal mesothelioma is a rare disease associated with poor prognosis. Acute abdomen as the first presentation is an extremely rare occurrence. We report an exceptional case of a patient who was found to have a jejunal perforation due to infiltration of peritoneal mesothelioma. METHODS: A 62-year-old man was admitted with clinical signs of peritonitis. Computerized tomographic scans showed a mass distal to the ligament of Treitz, thickening of the mesentery and a small amount of ascites. RESULTS: Emergency laparotomy revealed a perforated tumor 15 cm distal to the ligament of Treitz and diffuse peritoneal disease. Segmental small bowel resection and suboptimal cytoreduction were performed. Histopathology and immunohistochemistry showed infiltration of malignant mesothelioma. During the postoperative period pleural mesothelioma was also diagnosed. Despite adjuvant chemotherapy, the patient died of disseminated progressive disease 7 months after surgery. CONCLUSIONS: Peritoneal mesothelioma is a rare malignancy with grim prognosis. Small bowel involvement is a poor prognostic indicator. Our case of a small bowel perforation due to direct infiltration by peritoneal mesothelioma appears to be the first reported in the English literature. [source]

Asbestos-related cancers among 28,300 military servicemen in the Royal Norwegian Navy

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 1 2010
Leif Aage Strand MSc
Abstract Introduction This study focus on the incidence of asbestos-related cancers among 28,300 officers and enlisted servicemen in the Royal Norwegian Navy. Until 1987, asbestos aboard the vessels potentially caused exposure to 11,500 crew members. Methods Standardized incidence ratios (SIR) were calculated for malignant mesothelioma, lung cancer, and laryngeal, pharyngeal, stomach, and colorectal cancers according to service aboard between 1950 and 1987 and in other Navy personnel. Results Increased risk of mesothelioma was seen among engine room crews, with SIRs of 6.23 (95% CI,=,2.51,12.8) and 6.49 (95% CI,=,2.11,15.1) for personnel who served less than 2 years and those with longer service, respectively. Lung cancer was nearly 20% higher than expected among both engine crews and non-engine crews. An excess of colorectal cancer bordering on statistical significance was seen among non-engine crews (SIR,=,1.14; 95% CI,=,0.98,1.32). Land-based personnel and personnel who served aboard after 1987 had lower lung cancer incidence than expected (SIR,=,0.77; 95% CI,=,0.64,0.92). No elevated risk of laryngeal, pharyngeal, or stomach cancers was seen. Conclusion The overall increase (65%) in mesotheliomas among military Navy servicemen was confined to marine engine crews only. The mesothelioma incidence can be taken as an indicator of the presence or absence of asbestos exposure, but it offered no consistent explanation to the variation in incidence of other asbestos-related cancers. Am. J. Ind. Med. 53:64,71, 2010. © 2009 Wiley-Liss, Inc. [source]

Mesothelioma in a worker who spun chrysotile asbestos at home during childhood

Molecular characterization of tumour heterogeneity and malignant mesothelioma cell differentiation by gene profiling

Prevention of malignant seeding at drain sites by hypofractionated radiotherapy in patients with pleural mesothelioma

ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 3 2010
Pinar KARA
Abstract Aim: Unlike most other malignancies, malignant pleural mesothelioma (MPM) has a tendency to recur along tracks of chest wall instrumentation. We investigated the efficiency of hypofractionated radiotherapy for prevention of malignant seeding. Methods: Twenty-one (six female, 15 male) patients diagnosed with pleural mesothelioma who had chest wall instrumentation and were treated with prophylactic radiotherapy were investigated retrospectively. All patients underwent surgery or thoracoscopy and/or talc pleurodesis, for diagnosis, staging procedures or as a treatment. All were treated with electron (12 MeV) external beam radiation therapy (21 Gy in three fractions over 3 days), directed to the instrumentation pathway after the invasive procedure. After completion of radiotherapy, four of 21 patients had also undergone chemotherapy. Results: Nineteen of 21 patients were followed-up for a median period of 13 months (1,24 months) and two patients were lost just after the first month of the follow-up period. None of the followed patients had tumor progression in the treated area. Radiotherapy was well tolerated. The most common side-effect was grade 1 erythema (Radiation Therapy Oncology Group [RTOG] scale), noted in 13 treated patients. Conclusion: Our experience showed that prophylactic radiotherapy to prevent malignant seeding in malignant mesothelioma at invasive procedure sites was effective and well tolerated in preventing malignant seeding, painful metastases after surgery or instrumentation in patients with pleural mesothelioma. Larger multicenter prospective trials are still needed to validate this treatment approach utility for it to be recommended routinely. [source]

High-dose ifosfamide with mesna and granuloctye,colony-stimulating factor (recombinant human G-CSF) in patients with unresectable malignant mesothelioma

CANCER, Issue 2 2003
A Southwest Oncology Group study
Abstract BACKGROUND The current study was conducted to assess the activity and toxicity of high-dose ifosfamide and mesna with recombinant human granulocyte,colony-stimulating factor (rhG-CSF), given in an outpatient setting, in the treatment of patients with unresectable malignant mesothelioma. METHODS Between September 1994 and September 1996, 41 patients with histologically verified, unresectable malignant mesothelioma were registered, 38 of whom were analyzable (2 were ineligible and 1 was nonanalyzable). Patients received intravenous ifosfamide at a dose of 2.8 g/m2 over 3 hours (total dose of 14 g/m2), plus mesna at a dose of 0.56 g/m2 prior to and at 4 hours and 8 hours after ifosfamide infusion daily for 5 days every 21 days. rhG-CSF at a dose of 5 ,g/kg/day was administered subcutaneously on days 6,15. RESULTS Response assessment could be determined adequately in 21 patients. Two patients obtained responses; 1 was a confirmed partial response (3%; 95% confidence interval [95% CI], 0,14%) and 1 was an unconfirmed response (3%; 95% CI, 5,14%). Eleven patients had stable disease (29%), 7 patients developed disease progression (18%), 1 patient had an early death (3%), and 17 patients had inadequate assessment (45%). At the time of last follow-up, 36 of the 38 eligible patients had developed disease progression, with a median progression-free survival of 5 months (95% CI, 3,7 months) and 34 patients had died with a median survival of 7 months (95% CI, 6,9 months). Twenty-four patients (63%) and 7 patients (18%), respectively, had Grade (according to Southwestern Oncology Group Toxicity Criteria) 4 hematologic toxicities and Grade 4 nonhematological toxicities. There was one treatment-related death, the result of infection, pulmonary edema, and renal failure. CONCLUSIONS This regimen demonstrated a low overall objective response rate with substantial toxicity, and in the opinion of the authors does not warrant further investigation in the treatment of patients with unresectable malignant mesothelioma. Cancer 2003;98:331,6. © 2003 American Cancer Society. DOI 10.1002/cncr.11512 [source]

Diagnostic accuracy of cytology and immunocytology in carcinomatous effusions

CYTOPATHOLOGY, Issue 4 2008
G. Metzgeroth
Background:, Immunocytology substantially improves the diagnostic accuracy of conventional cytology in the diagnosis of carcinomatous effusions. Due to the unequivocal characterization of the various cell populations, a sensitivity of 92% and specificity of 100% was achieved by immunocytology, examining samples of 1234 serous effusions. Objective:, Cytology plays a central role in the aetiological clarification of serous effusions. The sensitivity of this method for the diagnosis of carcinomatous effusions varies between 40% and 80%. The aim of the present study was to investigate whether immunocytology substantially improves the diagnostic quality of the cytological examination in the diagnosis of carcinomatous effusions. Method:, Consecutive serous effusions were examined by conventional cytology and by immunocytology. The immunocytological examination was performed on smears, using a standard panel of three antibodies against pancytokeratin, human epithelial antigen 125 and calretinin. Results:, Altogether, 1234 effusion samples were examined. A total of 603 effusions were caused by carcinomas, five by malignant mesotheliomas, 11 by malignant lymphomas and 615 by non-malignant disorders. In conventional cytology, carcinomatous effusions were correctly diagnosed in 314 samples, corresponding to a sensitivity of 52%. In 31 specimens (5%) tumour cells without further specification were described and in 161 samples (27%) the presence of tumour cells was suspected (84% overall sensitivity). A total of 97 carcinomatous effusions (16%) were diagnosed false-negatively and 50 (8%) of the 615 non-malignant effusions false-positively (92% specificity). In immunocytology, 561 carcinomatous samples were correctly diagnosed, representing a sensitivity of 93%. In six cases (1%) the presence of tumour cells was suspected. A total of 36 carcinomatous effusions (6%) were diagnosed false-negatively (94% over-all sensitivity). Out of the 615 non-malignant specimens, there were no false-positive diagnoses (100% specificity). Conclusion:, Immunocytology is a simple, cost-effective, routinely practicable method which substantially improves the diagnostic accuracy of conventional cytology in the diagnosis of carcinomatous effusions. Therefore, we recommend the use of immunocytology in all those cases where cytology on its own is not completely unequivocal. [source]