Fate of Entosis: From the Beginning to the End in Untreated Advanced Breast Cancer

Homotypic entosis is a phenomenon in which one cancer cell invades a neighboring cancer cell and is closed entirely within its entotic vacuole. The fate of entosis can lead to inner cell death or survival. Recent evidence draws attention to entosis as a novel prognostic marker in breast cancer. Nevertheless, little is known about the quantity and quality of the process of entosis in human cancer specimens. Here, for the first time, we analyze the frequency of entotic figures in a case of NOS (Non-Other Specified) breast cancer with regard to location: the primary tumor, regional lymph node, and distant metastasis. For the identification of entotic figures, cells were stained using hematoxylin/eosin and assessed using criteria proposed by Mackay. The majority of entotic figures (65%) were found in the lymph node, 27% were found in the primary tumor, and 8% were found in the far metastasis. In the far metastases, entotic figures demonstrated an altered, atypic morphology. Interestingly, in all locations, entosis did not show any signs of cell death. Moreover, the slides were stained for E-cadherin or Ki67, and we identified proliferating (Ki67-positive) inner and outer entotic cells. Therefore, we propose additional criteria for the identification of pro-survival entotic structures in diagnostic histopathology.