Expression of snail, twist, and Zeb1 in malignant mesothelioma

Our plain-English summary of Expression of snail, twist, and Zeb1 in malignant mesothelioma, by H. Merikallio, P. Pääkkö, K. Salmenkivi, et al (APMIS, 2013).

The study

• Authors: H. Merikallio, P. Pääkkö, K. Salmenkivi, V. Kinnula, T. Harju, Y. Soini
• Journal: APMIS
• Published: 2013;121(1):1-10
• Cited by: 51 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

© 2012 The Authors APMIS © 2012 APMIS.

In plain English

This laboratory study examined tumor tissue from 56 malignant mesotheliomas (40 epithelioid, 6 sarcomatoid, 10 biphasic) from the University Hospitals of Oulu and Helsinki in Finland. The authors compared them with 117 lung adenocarcinomas and 34 adenocarcinomas that had spread to the lung from elsewhere. They stained the tissue for three proteins, snail, twist and zeb1, which are linked to epithelial–mesenchymal transition, a process in which epithelial cells take on mesenchymal features. The article did not report measuring or analyzing asbestos exposure. Zeb1 was found in 17 of 49 mesotheliomas (35%) and twist in 18 of 42 (43%). Both appeared more often than in lung adenocarcinomas (p less than 0.001 for both). Biphasic mesotheliomas showed snail and zeb1 more often than the other types combined. Mesothelioma patients whose tumors showed snail (17 of 56) had better survival (p = 0.046). In lung adenocarcinoma, snail went with poorer survival (p = 0.024). The authors concluded that the findings may indicate transformation between epithelioid and sarcomatoid cell types, with biphasic tumors in active transition. They noted that the sarcomatoid group was small. Some numbers differ between the article's text and tables.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Immunohistochemical (tissue staining) study of archived tumor samples arranged in tissue arrays, with survival analysis
• Who was studied: 56 malignant mesotheliomas from the files of the University Hospitals of Oulu and Helsinki, Finland (40 epithelioid, 6 sarcomatoid, 10 biphasic; ages 43–78; 16 women and 40 men), compared with 117 lung adenocarcinomas and 34 adenocarcinomas metastatic to the lung
• Exposure: The study measured staining for the proteins snail, twist, zeb1 and E-cadherin in tumor tissue. Asbestos appears only in the introduction, as a cause of the disease. The article did not report measuring or analyzing asbestos exposure.
• Main results:
  • In mesotheliomas, snail was positive in 17 of 56 cases (30%)
  • In mesotheliomas, zeb1 was positive in 17 of 49 cases (35%)
  • In mesotheliomas, twist was positive in 18 of 42 cases (43%)
  • Mesotheliomas had more zeb1-positive cases than lung adenocarcinomas (p less than 0.001)
  • Twist was more common in mesotheliomas than in lung adenocarcinomas (p less than 0.001)
  • The difference in snail between mesothelioma and lung adenocarcinoma was not statistically significant (p = 0.104)
  • Biphasic mesotheliomas showed snail or zeb1 more often than epithelioid and sarcomatoid mesotheliomas as a group (p = 0.034 and p = 0.005, respectively)
  • E-cadherin was more often present in epithelioid than in sarcomatoid or biphasic mesotheliomas (p = 0.0002 in the results text)
  • Snail-positive mesotheliomas had a lower apoptotic index, a measure of cell death (p = 0.039)
  • Mesothelioma patients with snail-positive tumors had better survival (p = 0.046, log rank)
  • In Cox regression analysis of mesothelioma patients, snail had independent prognostic value (p = 0.036)
  • In lung adenocarcinoma patients, snail pointed to poorer survival (p = 0.024)
  • Adenocarcinomas metastatic to the lung were more often positive for zeb1 and twist than primary lung adenocarcinomas (p less than 0.001 for both)
• The authors' conclusion: The authors concluded that the strong twist and zeb1 expression in mesothelioma may indicate transdifferentiation between epithelioid and sarcomatoid cell types, with biphasic mesotheliomas representing tumors in active transition
• Limitations the authors state:
  • With only six sarcomatoid cases, the lack of difference between sarcomatoid and epithelioid mesotheliomas may reflect the small numbers
  • The tissue array blocks ran out during staining, so case numbers varied between markers

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Lung Adenocarcinoma, Adenocarcinoma, Mesothelioma, Biphasic Mesothelioma, Epithelioid, Sarcomatoid, Prognosis.

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