Mesothelioma And Epithelial Differentiation

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.