Expression of snail, twist, and Zeb1 in malignant mesothelioma

Abstract

We examined 56 malignant mesotheliomas, 117 lung adenocarcinomas, and 34 metastatic lung adenocarcinomas with antibodies to transcription factors involved in epitheliomesenchymal transition. The tumors were stained immunohistochemically with antibodies zeb1, twist, and snail. Malignant mesotheliomas exhibited a stronger expression of zeb1 and twist than lung adenocarcinomas (p < 0.001 for both). Metastatic adenocarcinomas displayed a more frequent expression of zeb1 and twist (p < 0.001 for both) than lung adenocarcinomas. Patients with snail positive mesotheliomas experienced a better survival (p = 0.046), whereas in lung adenocarcinomas, this trait predicted worse survival (p = 0.024). Biphasic mesotheliomas had a more frequent expression of snail or zeb1 than epithelioid and sarcomatoid mesotheliomas as a group (p = 0.034 and p = 0.005, respectively). E-cadherin was more commonly present in epithelioid mesotheliomas (p = 0.002). Cases with snail positivity showed a significantly lower apoptotic index (p = 0.039). Malignant mesotheliomas display strong twist and zeb1 expression, which may be an indication of transdifferentiation between the epithelioid and sarcomatoid cell types with biphasic mesotheliomas representing tumors in active transition. Metastatic adenocarcinomas show a higher expression of zeb1 and twist than primary lung tumors, confirming our previous findings and highlighting their significance in the metastatic process. Snail expression is associated with poor prognosis in lung adenocarcinomas, but an opposite effect was seen in mesothelioma, a fact which may be related to the different cellular origin of epithelial and mesothelial cells.

Clinical Significance of Epithelial-Mesenchymal Transition-Associated Markers in Malignant Pleural Mesothelioma

“…First, positive expression of all of the EMT-related molecules (except fibronectin) was frequently expressed, similar to mesothelin [19] and osteopontin [20], in patients with MPM. Vimentin, Twist and YB-1 (mesenchymal markers) had a tendency to be slightly increased in sarcomatoid tumors compared to epithelioid tumors, which was consistent with the results of previous studies [10,11]. …”

“…Few studies have evaluated the prognostic value of EMT markers in MPM [8,9,10,11]. We hypothesized that the mesenchymal characteristics might predominate in the epithelioid-type tumors, and that the deregulated EMT status may indicate aggressive behavior in MPM.…”

Molecular Classification of Malignant Pleural Mesothelioma: Identification of a Poor Prognosis Subgroup Linked to the Epithelial-to-Mesenchymal Transition

“…Previous studies showed that epithelioid MPM had a higher level of expression of E-cadherin than the biphasic and sarcomatoid subtypes (52)(53)(54). However, the absence of E-cadherin expression in some subgroups of epithelioid MPM tumors despite their epithelial histologic features was previously observed by immunohistochemistry (52,54). In these studies, E-cadherin staining varied between 40% and 60%, which is in agreement with our classification of epithelioid MPM.…”

“…Regarding the molecular profile of the epithelioid MPM in the C2 subgroup, it may be suggested that these cells have undergone mesenchymal differentiation and acquired mesenchymal features, while still retaining some epithelial characteristics. Previous studies showed that epithelioid MPM had a higher level of expression of E-cadherin than the biphasic and sarcomatoid subtypes (52)(53)(54). However, the absence of E-cadherin expression in some subgroups of epithelioid MPM tumors despite their epithelial histologic features was previously observed by immunohistochemistry (52,54).…”

Twist expression in pleomorphic adenoma, adenoid cystic carcinoma and mucoepidermoid carcinoma of salivary glands

“…Twist expression was previously shown in some normal tissues such as prostate and breast (11,19). it was also demonstrated that this protein showed higher expression in malignant tumors compared to benign tumors such as prostate, parathyroid and lung (19)(20)(21). in the salivary gland tumors, there has been some investigation on Twist expression in adCCs and Pa.…”