Figure 4

Exploration of multiple brain metastases reveal a phenotypical concordance of CD271 expression. (A) Schematic representation of plausible mechanisms of primary tumor (PM) or extracranial metastasis (EM) seeding to the brain suggesting either a multiple or single seeding of PM/EM or a combination of both leading to high phenotypic heterogeneity (left and right scheme) or phenotypic homogeneity (center scheme). Brain schemes were obtained from Servier (http://servier.com/Powerpoint-image-bank) as per Servier’s usage license (https://creativecommons.org/licenses/by/3.0/legalcode) and modified. (B) Immunohistochemistry of autopsied multiple brain metastases. In patient T1, all tumors (n = 3) located in the cerebellum and frontal cortex showed strong expression of CD271. (C) Areas indicating CD271⁺ cell migration /invasion into adjacent brain parenchyma of tumors described in (B), are shown. Insets show distant CD271⁺ cells. (D) Exploration of brain micrometastases located in the hippocampus and cortex of patient T3 for presence of CD271⁺ cells (black arrows).