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Review
. 2018 May 30;19(6):1603.
doi: 10.3390/ijms19061603.

Heterogeneity in Malignant Pleural Mesothelioma

Kathrin Oehl  1   2 , Bart Vrugt  3 , Isabelle Opitz  4 , Mayura Meerang  5
Affiliations
Review

Heterogeneity in Malignant Pleural Mesothelioma

Kathrin Oehl et al. Int J Mol Sci. .

Abstract

Despite advances in malignant pleural mesothelioma therapy, life expectancy of affected patients remains short. The limited efficiency of treatment options is mainly caused by inter- and intra-tumor heterogeneity of mesotheliomas. This diversity can be observed at the morphological and molecular levels. Molecular analyses reveal a high heterogeneity (i) between patients; (ii) within different areas of a given tumor in terms of different clonal compositions; and (iii) during treatment over time. The aim of the present review is to highlight this diversity and its therapeutic implications.

Keywords: cancer stem cells; chemoresistance; inter-tumor heterogeneity; mesothelioma; spatial intra-tumor heterogeneity; targeted therapy; temporal intra-tumor heterogeneity.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Morphological and immunohistochemical heterogeneity in mesothelioma. (A) Biphasic mesothelioma consisting of an epithelioid and sarcomatoid component (H&E stain), highlighted by a calretinin staining (B) showing a weaker expression in the sarcomatoid proliferation. (C) Heterogeneous expression of BAP-1 with positive nuclear staining in the sarcomatoid component and loss of BAP-1 expression in the epithelioid areas of the tumor. All pictures were taken at 10× magnification (scale bar: 100 µm).
Figure 2
Figure 2
Models of tumor heterogeneity. In the clonal evolution model (upper panel) all cells are able to replicate (indicated by “R”). Mutations (colored arrows) are gained over time, leading to the formation of subclones which results in a heterogeneous tumor. In the cancer stem cell (CSC) model with clonal evolution, only CSCs are able to replicate. However, mutations occurring over time lead to the formation of additional CSCs.
See this image and copyright information in PMC

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