Mesothelioma Research and Results

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.

CONCLUSIONS: The presence of N2 disease negatively affects the prognosis of patients with malignant pleural mesothelioma. Mediastinoscopy, however, seems to have a limited role in patient selection for extrapleural pneumonectomy. Adjuvant hemithoracic radiation therapy but not N2 disease affects the risk of locoregional recurrence.

Another interesting study is called, "Malignant mesothelioma: cytologic diagnosis with histologic, immunohistochemical, and ultrastructural correlation." by Leong AS, Stevens MW, Mukherjee TM - Division of Tissue Pathology, Institute of Medical and Veterinary Science, Adelaide, South Australia. - Seminars in Diagnostic Pathology 1992, 9(2):141-50.  Here is an excerpt: "Abstract - The differential diagnoses of malignant mesothelioma in serous effusions include adenocarcinoma and reactive mesothelial cells. While several cytologic features are of predictive value in separating these entities, immunostaining and ultrastructural examination are important adjuncts that increase the diagnostic yield. Many of the cytomorphologic features can be correlated with immunohistochemical and ultrastructural findings. Most important among these is the ultrastructural demonstration of long, often branching microvillous processes in malignant mesothelial cells. Corresponding microvilli can be visualized by immunostaining for epithelial membrane antigen in both cell block preparations from effusions and biopsy specimens, allowing the identification of malignant mesothelioma. In addition, the circumferential distribution of these immunostained microvilli in cells dispersed in stromal connective tissue identifies them as malignant mesothelial cells, corresponding to the ultrastructural appearance of aberrant microvilli, which project through deficiencies in the basal lamina. These microvilli show interdigitation with stromal collagen fibers, a phenomena not observed in adenocarcinoma."

Another study is called, "Expression profile of telomerase subunits in human pleural Mesothelioma" by Karl Dhaene, Jan Wauters, Barbara Weyn, Jean-Pierre Timmermans, Eric van Marck, - The Journal of Pathology Volume 190, Issue 1, pages 80–85, January 2000.  Here is an excerpt: "Abstract - Using the TRAP assay, telomerase activity was previously detected in over 90% of human pleural mesotheliomas (MMs), but not in mesothelial cell cultures (MCCs), suggesting that telomerase re-activation occurs during multi-step mesothelioma carcinogenesis. The present study determined the expression of the telomerase RNA template (hTERC), the telomerase-associated protein (hTEP1), and the telomerase catalytic sub-unit (hTERT), in 16 pleural MMs and 4 MM-derived cell lines, in two pleural solitary fibrous tumours and in six MCCs. Reverse transcription-polymerase chain reaction analysis revealed that hTERT mRNA expression parallels the activity status documented by the TRAP assay, whereas hTERC and hTEP1 mRNA are commonly expressed in all malignant and non-malignant serosal cells and tissues. Three alternatively spliced hTERT transcripts were detected in all telomerase-positive samples, whereas neither variant could be detected in the MCCs. Detection of the hTERT protein with a commercially available antibody was not successful. These results indicate that hTERT expression is rate-limiting for human telomerase activity and that re-activation, rather than up-regulation, of hTERT expression can play a critical role in MM carcinogenesis. While waiting suitable anti-hTERT antibodies, these results provide information for the design of hTERT mRNA-specific in situ probes to study telomerase in archived pre-malignant serosal 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.