Tenascin-X is a Novel Diagnostic Marker of Malignant Mesothelioma

Abstract

TNXB was previously identified as a gene that is more highly expressed in malignant mesothelioma compared to ovarian/peritoneal serous carcinoma based on gene expression array analysis. The objective of the present study was to validate this finding at the mRNA and protein level. Effusions (n=91; 71 ovarian carcinomas, 10 breast carcinomas, 10 malignant mesotheliomas) were assayed for TNXB mRNA expression using quantitative PCR. Tenascin-X protein expression was studied in 183 effusions (137 carcinomas of different origin, 37 mesotheliomas, 9 reactive effusions) and 178 solid lesions (122 ovarian/ peritoneal carcinomas, 56 mesotheliomas) using immunohistochemistry. Quantitative PCR analysis showed significantly higher TNXB mRNA level in mesotheliomas compared to ovarian and breast carcinomas (p<0.001). By immunohistochemistry, tenascin-X protein expression was significantly higher in malignant mesothelioma compared to metastatic carcinoma in effusions (34/37 vs. 31/137 positive cases; sensitivity = 92%, specificity = 77%; p<0.001). Reactive mesothelial cells had focal or no tenascin-X expression. Tenascin-X protein was detected 41/56 mesothelioma biopsy specimens, and was uniformly absent from all 122 ovarian carcinomas (sensitivity = 73%, specificity = 100%; p<0.001). Our data suggest that tenascin-X may be a new diagnostic marker of malignant mesothelioma in the differential diagnosis of cancers involving the serosal cavities, particularly in the differential diagnosis between this tumor and ovarian/peritoneal serous carcinoma.

Non-steroidal anti-inflammatory drugs target the pro-tumorigenic extracellular matrix of the postpartum mammary gland

“…Whereas TN-C has been shown to directly signal to a variety of normal and transformed cell types to increase migration, few studies have investigated potential roles for tenascin-X in tumor progression. Transcript and protein expression studies do not display a distinct relationship, as tenascin-X is upregulated in malignant mesothelioma and in the serum of breast cancer patients, but downregulated in melanoma and neurofibromatosis type-1 associated tumors (Geffrotin et al, 2000;Levy et al, 2007;Yuan et al, 2009;Zeng et al, 2011). Our current proteomic analyses revealed that tenascin-X is downregulated during postpartum involution in mammary ECM compared to nulliparous levels, and then upregulated with postpartum ibuprofen treatment (data not shown), suggesting further study of tenascin-X function is of interest.…”

Pre-analytical issues in effusion cytology

“…This material has been extensively used for both gene expression array analyses of different cancers affecting the serosal cavities [73][74][75] and validation studies of the array data using qPCR [76][77][78][79][80][81][82].…”

18th International Congress of Cytology Paris, France, May 26-30, 2013

“…The age ranged from 3 to 77 years with a mean age of 46.5 years. The most common fungal organism identified was aspergillus (36; 61%) followed by candida (10) and pneumocystis (9). Three cases of cryptococcus and 1 case of histoplasma were also recognized.…”

“…In order to detect PAX8/PPARg rearrangements we performed a 4-colors PCR (Algeciras-Schimnich et al 2010) followed by HFRA. This assay was designed to detect 4 distinct rearrangements involving different PAX8 DNA breakpoints (exons 8,9,10,[8][9][10]. A cohort of fixed histological (FFPE) samples were also analyzed.…”