Diagnostic Specificity Asbestos Exposure and Mesothelioma Disease

An interesting study called  “Latent Period for Malignant Mesothelioma of Occupational Origin” by Lanphear, Bruce P. MD, MPH; Buncher, C. Ralph ScD has objectives to estimate the minimal latent period for malignant mesothelioma of occupational origin, we reviewed 21 articles that documented latent periods for malignant mesothelioma, totaling 1690 cases. About 1105 cases fullfiled the strict histologic and exposure criteria and were included in this analysis. Of these mesotheliomas, 99% had a latent period more than 15 years; 96% had a latent period of at least 20 years. The probability of first exposure of an occupational within a decade was zero. After the initial exposure, estimated median latent period was at least 32 years. These are improtatnt conclusions as they can help in determining the source of a specific case of the disease, understanding the natural history of the disease, determining liability, and in aiding in the diagnosis of malignant mesotheliomas of occupational origin.

Phase II Trial of a Single Weekly Intravenous Dose of Ranpirnase in Patients With Unresectable Malignant Mesothelioma” by Stanislaw M. Mikulski, John J. Costanzi, Nicholas J. Vogelzang, Spence McCachren, Robert N. Taub, Hoo Chun, Abraham Mittelman, Timothy Panella, Carmelo Puccio, Robert Fine, Kuslima Shogen – Journal of Clinical Oncology, Vol 20, Issue 1 (January), 2002: 274-281. Here is an excerpt: “ABSTRACT – PURPOSE: A multicenter phase II trial of ranpirnase (Onconase; Alfacell Corp, Bloomfield, NJ) as a single agent was conducted to further assess the safety and clinical efficacy of this novel antitumor ribonuclease. Patients with unresectable and histologically confirmed malignant mesothelioma (MM) were eligible.

The research sample and metods were used one hundred five patients with Eastern Cooperative Oncology Group performance status 0 to 2 were enrolled onto the study. Thirty-seven percent of patients had not responded to prior chemotherapy. The primary end point of the study was survival. Tumor responses and time to progression were also assessed. The Cancer and Leukemia Group B (CALGB) prognostic group criteria were used to define a treatment target group (TTG). Both the intent-to-treat (ITT) and the TTG populations were analyzed for survival.

Another interesting study is called, “Thrombomodulin expression in malignant pleural mesothelioma and pulmonary adenocarcinoma.” By C. L. Collins, N. G. Ordonez, R. Schaefer, C. D. Cook, S. S. Xie, J. Granger, P. L. Hsu, L. Fink, and S. M. Hsu Am J Pathol. Here is an excerpt: Thrombomodulin (TM) is a glycoprotein of molecular weight 75,000 kd that is normally present in restricted numbers of cells, including endothelial and mesothelial cells. In this study, the authors tested the possibility of using anti-TM to facilitate the diagnosis of mesothelioma. All of the 31 mesotheliomas and the two mesothelioma cell lines (MS-1 and MS-2) tested were stained positively with anti-TM. In situ hybridization of MS-1 cells with a TM-specific probe was confirming the specify of anti-TM staining in mesothelioma cells. The expression of TM in MS-1 cells was increased markedly when these cells were induced by 12-0-tetradecanyl phorbol 13-acetate (TPA) to differentiate.

However, the expression of TM in mesothelioma cells did not correlate with any particular phase of the cell cycle. The researchers compared compared the expression of TM, carcinoembryonic antigen (CEA), and Leu M1 in these two types of tumors in an attempt to differentiate pleural mesothelioma from pulmonary adenocarcinoma. Antibodies to TM stains positively four of 48 (8%) pulmonary adenocarcinomas. Therefore, immunohistochemical staining with antibodies to TM yielded 100% sensitivity and 92% specificity for diagnosis of mesothelioma. All of the mesotheliomas stained negatively for CEA and Leu M1, except for one, which showed minimal focal positivity for Leu M1. In contrast, 79% and 60% of adenocarcinomas stained positively for CEA and Leu M1, respectively. These findings suggest that immunocytochemical staining with anti-TM should be added to the battery of tests to increase the diagnostic sensitivity and specificity for differentiating mesothelioma from pulmonary adenocarcinoma.

Read the studies in entirety if you find these helpful and interesting.  We all owe a great debt to these researchers for their important work.



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