Criteria That Are Sufficient To Identify Mesothelioma With High Specificity Information

One study is called, “Immunohistochemical reactivity in mesothelioma and adenocarcinoma: A stepwise logistic regression analysis” by Annika Dejmek, Anders Hjerpe - 1994 Acta Pathologica, Microbiologica et Immunologica Scandinavica – APMIS Volume 102, Issue 1-6, pages 255–264, January 1994. Here is an excerpt: “Histological sections from 103 malignant mesotheliomas and 43 adenocarcinoma metastases in pleural biopsies were investigated for reactivity against a panel of 11 different antibodies. The size of the material allowed the evaluation by stepwise logistic regression analysis, which selected five parameters of major importance: vimentin reactivity in epithelial cells, reactivity to low-molecular-weight keratins in fibrous cells, strong membrane accentuation of EM A reactivity, and lack of reactivity to LeuM1 and BerEp4. Three of these criteria were sufficient to identify a mesothelioma with high specificity and with a sensitivity of approximately 70%. Whilst the monoclonal anti-CEA tested was the most valuable single parameter, it did not add any diagnostic information to the combination of criteria selected by the stepwise logistic regression analysis. However, this antibody can be used to exclude most of the adenocarcinomas from further analysis with the more extensive panel.”

Another study is called, “Ectopic thymoma mimicking diffuse pleural mesothelioma: A case report” - Volume 29, Issue 4, Pages 409-410 (April 1998) by Hiroaki Fushimi, MD, Yoshiro Tanio, MD, Kiyoshi Kotoh, MD. Here is an excerpt: “Abstract - A case of ectopic thymoma of the pleura with a particular growth pattern mimicking diffuse pleural mesothelioma is reported. Diagnostic imaging showed that the pleural tumor encased the entire left lung. The specimen biopsied from the tumor was composed of lymphocytes and epithelial cells, consistent with the mixed type of thymoma. The autopsy found no evidence of a mediastinal tumor. An involuted thymus was found in the parietal pleural tissue adhered to the apex of the left lung. The thymoma was thought to originate from the ectopic thymic tissue in the parietal pleura, as a lesion independent from the primary mediastinal thymoma, and spread along the pleura like diffuse mesothelioma.

Another study is called, “Dose-Dependent Pulmonary Toxicity After Postoperative Intensity-Modulated Radiotherapy for Malignant Pleural MesotheliomaPresented at the 48th Annual Meeting of the American Society for Therapeutic and Radiation Oncology (ASTRO), Philadelphia, PA, November 5–9, 2006. - International Journal of Radiation Oncology Biology Physics - Volume 69, Issue 2 , Pages 350-357, 1 October 2007 by

David C. Rice, M.B., B.Ch. Affiliations - Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX. Here is an excerpt: “Purpose: To determine the incidence of fatal pulmonary events after extrapleural pneumonectomy and hemithoracic intensity-modulated radiotherapy (IMRT) for malignant pleural mesothelioma. Methods and Materials: We retrospectively reviewed the records of 63 consecutive patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy and IMRT at the University of Texas M. D. Anderson Cancer Center. The endpoints studied were pulmonary-related death (PRD) and non–cancer-related death within 6 months of IMRT.

Results: Of the 63 patients, 23 (37%) had died within 6 months of IMRT (10 of recurrent cancer, 6 of pulmonary causes [pneumonia in 4 and pneumonitis in 2], and 7 of other noncancer causes [pulmonary embolus in 2, sepsis after bronchopleural fistula in 1, and cause unknown but without pulmonary symptoms or recurrent disease in 4]). On univariate analysis, the factors that predicted for PRD were a lower preoperative ejection fraction (p = 0.021), absolute volume of lung spared at 10 Gy (p = 0.025), percentage of lung volume receiving e20 Gy (V20; p = 0.002), and mean lung dose (p = 0.013). On multivariate analysis, only V20 was predictive of PRD (p = 0.017; odds ratio, 1.50; 95% confidence interval, 1.08–2.08) or non–cancer-related death (p = 0.033; odds ratio, 1.21; 95% confidence interval, 1.02–1.45).

Conclusion: The results of our study have shown that fatal pulmonary toxicities were associated with radiation to the contralateral lung. V20 was the only independent determinant for risk of PRD or non–cancer-related death. The mean V20 of the non-PRD patients was considerably lower than that accepted during standard thoracic radiotherapy, implying that the V20 should be kept as low as possible after extrapleural pneumonectomy.

Mesothelioma And Ephitelial Differentiation Information

One interesting study is called, “Proteoglycans in human malignant mesothelioma. Stimulation of their synthesis induced by epidermal, insulin and platelet-derived growth factors involves receptors with tyrosine kinase activity” – Biochimie Volume 81, Issue 7, July 1999, Pages 733-744 – by Alexandra Syrokoua, George N. Tzanakakisb, Anders Hjerpeb and Nikos K. Karamanosa - Department of Chemistry, University of Patras, 261 10 Patras, Greece. Here is an excerpt: “Abstract - Identification of proteoglycans in two human malignant mesothelioma cell lines, one with epithelial differentiation and the other with fibroblast-like phenotype, and the effects of epidermal (EGF), insulin-like (IGF-I) and platelet-derived (PDGF-BB) growth factors on the synthesis of hyaluronan (HA) and proteoglycans (PGs) were studied. Both cell lines synthesize HA and PGs: these last were recovered both as secreted and cell-associated compounds. Chondroitin sulfate (CS) containing PGs are mainly organized as versican in the extracellular medium and as thrombomodulin and syndecan in the cell membrane. Heparan sulfate (HS) containing PGs are mainly in the form of perlecan in the culture medium, whereas cell-associated HSPGs were recovered mainly as syndecan-1, -2 and -4. Receptors for EGF, IGF-I and PDGF-BB were identified in both cell lines. In addition to cell proliferation, these growth factors stimulated the synthesis of HA and PGs, the pattern of stimulation being unique for each of them and depending on the cell phenotype. EGF increased the synthesis of HA and PGs. IGF-I showed similar stimulatory effects on the synthesis of CSPGs, whereas higher amounts were needed to influence the synthesis of HA and HSPGs, the latter only being stimulated in the epithelial cell line. PDGF-BB stimulated the synthesis of HA, HSPGs and CSPGs at low concentrations, while the stimulatory effect was abolished at higher levels. Incubation with genistein inhibited the HA and PG synthesis induced by growth factors in a mode depending on both growth factor and genistein concentrations. The results clearly suggest that the stimulatory effects of EGF, IGF-I and PDGF-BB on matrix synthesis, expressed as proteoglycan synthesis, are mediated via receptor-growth factor complexes and the protein tyrosine kinase intracellular pathway.

Another study is called, “Value of E-cadherin and N-cadherin immunostaining in the diagnosis of Mesothelioma” by ORDONEZ Nelson G. 2, Allée du Parc de Brabois F-54514 Vandoeuvre-lès-Nancy – Cedex France. Here is an excerpt: “Abstract - Distinguishing between epithelioid mesothelioma and pulmonary adenocarcinoma involving the pleura can be difficult on routine histological preparations. This differential diagnosis can be greatly facilitated by using immunohistochemical markers. E-cadherin and N-cadherin are among the newly described markers that have been proposed as potentially useful in the diagnosis of mesothelioma. E-cadherin and N-cadherin are members of the cadherin family of calcium-dependent cell adhesion molecules that play an important role in the embryogenic development and maintenance of normal tissue. Although several investigations have indicated that immunostaining for these markers can be useful in discriminating between mesotheliomas and adenocarcinomas, others have not confirmed this observation. In an attempt to resolve this controversy, the present study investigated 31 epithelioid mesotheliomas and 29 pulmonary adenocarcinomas for E-cadherin and N-cadherin expression using the 5H9, HECD-1, and clone 36 anti-Ewadherin antibodies, and the 3B9 and clone 32 anti-N-cadherin antibodies. Among the mesotheliomas, 68% reacted with the clone 36, 52% reacted with the HECD-1, and 19% reacted with the 5H9 anti-Ecadherin antibodies, and 74% reacted with the 3B9 and 71% reacted with the clone 32 anti-N-cadherin antibodies. Of the adenocarcinomas, 93% stained with the done 36, 90% reacted with the HELD-1, and 90% reacted with the 5H9 anti-Ecadherin antibodies, 45% reacted with the clone 32 and 34% reacted with the 3B9 anti-N-cadherin antibodies. Based on the frequent strong reactivity with adenocarcinomas but not with mesotheliomas, it is concluded that only the 5H9 anti-Ecadherin antibody may have some utility in discriminating between epithelioid pleural mesotheliomas and pulmonary adenocarcinomas. The causes of the disparate results reported in the literature on the value of E-cadherin and N-cadherin immunostaining in distinguishing between mesotheliomas and pulmonary adenocarcinomas are unclear, but a significant factor appears to be differences in the reactivity of the antibodies used.”

Another study is called, “The value of Wilms tumor susceptibility gene 1 in cytologic preparations as a marker for malignant Mesothelioma” by Jonathan L. Hecht M.D., Ph.D., Benjamin H. Lee M.D., Ph.D., Jack L. Pinkus Ph.D., Geraldine S. Pinkus M.D., - Cancer Cytopathology Volume 96, Issue 2, pages 105–109, 25 April 2002. Here is an excerpt: “Abstract - It has been shown that detection of the Wilms tumor susceptibility gene 1 protein (WT1) has diagnostic utility in the distinction of mesothelioma from adenocarcinoma in tissue sections of pleural tumors. This immunohistochemical study evaluates the effectiveness of WT1 as a marker for malignant mesothelioma in paraffin sections of cell block preparations derived from effusion specimens. METHODS The authors evaluated 111 cell blocks for WT1 immunoreactivity, including 14 mesotheliomas and 97 metastatic adenocarcinomas from various sites. RESULTS Nuclear reactivity for WT1 was observed in all samples of mesothelioma. However, only 22 of 97 samples (23%) of metastatic adenocarcinoma, nearly all of which were of ovarian origin (91%), exhibited nuclear reactivity for WT1. In 14 other samples (most of pulmonary derivation), WT1 staining restricted to the cytoplasm was observed for some tumor cells and was regarded as nonspecific. CONCLUSIONS - Based on this staining profile, WT1 represents an effective marker for mesotheliomas in cell block preparations and can aid in its distinction from pulmonary adenocarcinoma. In assessment of effusion specimens with metastatic carcinoma, nuclear reactivity for WT1 is highly suggestive of an ovary primary tumor.

Wilms tumor susceptibility gene 1 is a tumor suppressor gene that initially was identified due to its deletion or mutation in Wilms tumors. Monoclonal antibodies to its protein product, WT1, were developed subsequently, and it was found that they had diagnostic utility not only in the identification of Wilms tumors and desmoplastic small round cell tumors1, 2 but also in the distinction of mesothelioma from adenocarcinoma in pleural tumors.3, 4 This immunohistochemical study evaluates the diagnostic utility of WT1 as a marker for malignant mesothelioma in paraffin sections of cell block preparations derived from effusion specimens. Cancer (Cancer Cytopathol) 2002;96:000–000.

Lession Simulating Malignant Pleural Mesothelioma

One interesting study is called, “Absence of SV40 large T-antigen expression in human mesothelioma cell lines.” By Pilatte Y, Vivo C, Renier A, Kheuang L, Greffard A, Jaurand MC - Am J Respir Cell Mol Biol. 2000 Dec;23 (6):788-93. - INSERM, Créteil, France. Here is an excerpt: “Abstract - Simian virus (SV) 40 and SV40-like DNA sequences have recently been detected in several types of human tumors, including malignant mesothelioma. However, the presence of SV40 DNA sequences is not sufficient to account for its possible role in tumor development because the viral proteins must be expressed and ultimately impair the function of relevant cell proteins, such as p53 and pRb. In this study we investigated SV40 large T antigen (SV40 Tag) protein expression in mesothelioma cell lines, established in our laboratory, by Western blotting, immunoprecipitation, and immunocytochemistry using Tag-specific mouse monoclonal antibodies (mAbs) Ab-1 (or Pab 419). By Western blotting of cell extracts, none of the mesothelioma cell lines expressed detectable amounts of SV40 Tag. However, we found that Ab-1 as well as Pab-101, another SV 40 Tag-specific mAb, may generate false-positive signals due to the fact that both antibody preparations are contaminated by a protein of similar size (90 kD) as SV40 Tag and react with the various secondary horseradish peroxidase- conjugated antimouse immunoglobulin Gs tested. The present study suggests that immunodetection of SV40 Tag protein may be puzzling because this contaminating Taglike protein may bind to particular cell structures, thereby generating false-positive signals.”

Another study is called, “Pseudomesotheliomatous angiosarcoma: a pleuropulmonary lesion simulating malignant pleural Mesothelioma” by G. Falconieri, R. Bussani1, M. Mirra, M. Zanella – Histopathology Volume 30, Issue 5, pages 419–424, May 1997. Here is an excerpt: “We report two cases of autopsy confirmed angiosarcoma in adult males, presenting as diffuse pleuropulmonary tumours and simulating malignant mesothelioma. Both the lesions grew along the serosal surfaces and were characterized by variably thick rinds of tissue encasing the lung. The pulmonary parenchyma showed diffuse, dark red, subpleural consolidations and multiple cavitations. Histologically, the lesions were composed by atypical spindle and polygonal, epithelioid cells showing rudimentary vascular differentiation and exhibiting strong positivity for factor VIII, CD31, CD34 and vimentin. We conclude that angiosarcoma may present with preponderant or exclusive involvement of pleura and peripheral lung and that it should be added to the list of tumours capable of simulating malignant mesothelioma.”

Another study is called, “D2-40: A Reliable Marker in the Diagnosis of Pleural Mesothelioma” by Annette M. Müllera, Folker E. Frankeb, Klaus-Michael Müllera - Institute of Pathology, BG Clinics ‘Bergmannsheil’, Ruhr University Bochum, Bochum, and Justus Liebig University, Giessen, Germany - Pathobiology 2006;73:50-54. Here is an excerpt: “Abstract - Objective: Malignant mesotheliomas of the pleura, peritoneum and pericardium can easily be confused with either metastatic adenocarcinomas or reactive pleural lesions. D2-40, a monoclonal antibody used as a marker for seminomatous germ cell tumours and lymphatic endothelial cells, was recently described in mesothelial cells and type I but not type II pneumocytes. Method: The immunoreactivities of D2-40 in 76 lung carcinomas of different histological types (adenocarcinomas, squamous cell, small cell, and bronchioloalveolar carcinomas) were compared with those of 36 pleural epithelioid and sarcomatoid mesotheliomas and 5 specimens of chronic pleuritis. Results: While all 18 analysed epithelioid mesotheliomas displayed a strong membranous immunostaining, 18 sarcomatoid mesotheliomas showed no, or a merely faint, cytoplasmic signal, comparable with fibroblasts in chronic pleuritis. Out of all analysed lung carcinomas, 49 showed no immunoreactivity for D2-40 (64%), while the other 27 (36%) showed a focal weak to moderate and only cytoplasmic signal. Conclusions: We regard D2-40 as a valid marker in the differential diagnosis of epithelioid mesotheliomas versus pulmonary adenocarcinomas. However, this marker may not properly label sarcomatoid mesotheliomas or distinguish them from reactive pleural lesions.”

We all owe a debt of gratitude to these fine researchers. If you found any of these excerpts interesting, please read the studies in their entirety.

Mesothelioma And Cancer Gene Therapy Information

One interesting study is called, “Adenovirus-mediated wild-type p53 overexpression reverts tumourigenicity of human mesothelioma cells.” By Giuliano M, Catalano A, Strizzi L, Vianale G, Capogrossi M, Procopio A. Int J Mol Med. 2000 Jun;5(6):591-6. Department of Oncology and Neuroscience, Clinical Pathology Section, Gabriele D'Annunzio University, 66013 Chieti, Italy. Here is an excerpt: “Abstract - Pleural malignant mesothelioma (MM) shows poor survival, regardless of tumour stage at diagnosis. MM is unresponsive to present treatment regimens and new protocols are desperately needed. The localised nature, the potential accessibility, and the relative lack of distant metastases make MM a particularly attractive candidate for somatic gene therapy. A common target for cancer gene therapy is the tumour suppressor protein p53. p53 does not seem to be mutated or deleted in MM, but it can be inactivated by binding to other proteins, like mdm2 and SV40 large T antigen. We tested the effects of a replication-deficient adenoviral vector carrying wild-type p53 cDNA in human MM cells. Our results show that >95% of MM cells were efficiently infected with 25 multiplicity of infection (MOI) of vector. Wild-type p53 was effectively expressed resulting in >80% inhibition of proliferation in MM cells. AdCMV.p53 infection induced apoptosis while controls did not show any evident morphological alterations. Ex vivo p53 gene transfer experiments inhibited tumourigenesis in nude mice. In vivo, direct intratumour injection of AdCMV.p53 arrested tumour growth and prolonged survival of treated mice. These results indicate that p53-gene therapy should be strongly exploited for clinical trials in MM patients.”

Another study is called, “Congenital polycystic tumor of the atrioventricular node (endodermal heterotopia, mesothelioma): A histogenetic appraisal with evidence for its endodermal origin” - Human Pathology Volume 18, Issue 8, August 1987, Pages 791-795 by MD Gerald Fine and MD Usha Raju. Here is an excerpt: “The small, variously designated, primary atrioventricular node tumor has been considered to be of endothelial, endodermal, or mesothelial origin. To identify its derivation, we studied seven tumors using silver staining and immunocytochemical labeling with a variety of antibodies. Cytoplasmic argyrophil granules but not argentaffin granules were found in isolated cells among the more numerous bubule-lining cells in four tumors. Serotonin and calcitonin were demonstrable in seven and six tumors, respectively, in a similar distribution to that of the argyrophil cells. A positive reaction of different distribution from that of the argyrophil cells was noted in a varying number of tubule-lining cells for carcinoembryonic antigen, epithelial membrane antigen, and blood group antigen in seven, four, and seven tumors, respectively. No activity was noted in the tumor cells for factor VIII-related antigen or a number of peptides. An endodermal rather than mesothelial or epithelial origin for the tumor is substantiated by the presence of neuroendocrine cells in the midst of the more numerous carcinoembryonic-antigen-positive lining cells of the tumor tubules.”

Another study is called, “SV40 expression in human neoplastic and non-neoplastic tissues: perspectives on diagnosis, prognosis and therapy of human malignant mesothelioma.” By Procopio A, Marinacci R, Marinetti MR, Strizzi L, Paludi D, Iezzi T, Tassi G, Casalini A, Modesti A. Dev Biol Stand. 1998;94:361-7. Department of Oncology and Neuroscience, Gabriele D'Annunzio University, Chieti, Italy. Here is an excerpt: “Abstract - We have recently demonstrated the association of SV40 and human pleural malignant mesothelioma. Here, we have investigated whether SV40 viral sequences may be associated with other human tumours or other non-neoplastic pathology and whether SV40 DNA or protein expression may be of diagnostic, prognostic or therapeutic relevance. DNA was extracted from paraffin embedded tissues. SV40, JC and BK viral sequences were detected by the polymerase chain reaction and molecular hybridization with specific probes. The screening with three different sets of SV40-related primers demonstrated that 7/18 (38.8%) mesothelioma specimens were SV40 positive as well as 5/18 (27.7%) tubercular pleural lesions. None of the 18 lung cancers, nor the 20 pleural non-specific inflammatory specimens tested were positive. Twenty-five blood samples and 18 urinary sediments from MM patients were also negative. We have also found that SV40 Tag proteins are present in mesothelioma cells and tumours. Tag proteins may interfere with tumour suppressor gene products, such as p53. Preliminary results suggest that wild type p53 transgene expression, obtained after infection with recombinant adenovirus (AdCMV.p53), inhibited in vitro and in vivo proliferation, inducing apoptosis of mesothelioma cells. Infections with control viruses were ineffective. Thus, SV40 DNA and Tag expression in mesothelioma tumour cells, though probably not relevant for diagnostic or prognostic purposes, may be crucial for innovative gene therapy strategies.”

Some Basics Detail Of A Mesothelioma Lawsuit Information

Unfortunately, our world is one in which exist a number of organizations and individuals who may injure a person through misconduct and negligence. Quite often, a mesothelioma lawsuit may seek compensation from more than one defendant. In fact, there have been many notable asbestos cases with 40 or more defendants. Defendants are selected based on past occupational and environmental risks. This is typical in a mesothelioma lawsuit, because many individuals possess a history with several different manufacturers and employers. These relationships establish the basis of a client’s (or plaintiff’s) complaint that officially comprises the initiation of a mesothelioma lawsuit.

There are basically two plaintiff types in a mesothelioma lawsuit. These include one type, in which, the actual affected individual(s) begins a mesothelioma lawsuit in an effort to receive damages for their injuries. This type of mesothelioma lawsuit is known as a personal injury lawsuit for living victims of asbestos exposure. The second type involves family, such as a spouse or children, and is most frequently referred to as a wrongful death lawsuit. As the mesothelioma lawsuit progresses, each defending party will respond to the complaint entered in court. These answers are reviewed by the plaintiff and each party enters into a discovery process that may include a number of interrogatories, depositions, record releases and witness testimony; among other items.

The average mesothelioma lawsuit is settled before it goes all the way to trial. However, the progression of each case is an individual process that may continue through jury selection and perhaps, even hours before the actual jury trial is scheduled before a defendant offers a mesothelioma settlement. Often, the dates leading up to a trial are stressful and anxious for all involved parties.

Once a mesothelioma settlement is granted, payment may be provided in varying time frames. This is largely because many companies charged with misconduct are also paying damages to others for similar personal injuries. It is not unheard of, for payouts to occur in time periods spanning from several months to years after the agreed upon mesothelioma settlement. In some lamentable cases, a defendant may file bankruptcy, further prolonging the likelihood of payment delivery. There are also some lawsuits that result in a schedule of multiple payments for damages rendered.

Anyone that knows a mesothelioma victim should spend some time researching the potential for a personal injury or wrongful death case. Although a monetary settlement could never replace a loved one, it sometimes offers comfort to individuals facing this terminal illness, to know that their family will receive restitution that is substantial enough to make a positive impact in their lives. Trust the mesothelioma lawyers at Baron and Budd, P.C. for total guidance through the process of a mesothelioma lawsuit.