Searching for SARS-CoV-2 in Cancer Tissues: Results of an Extensive Methodologic Approach based on ACE2 and Furin Expression

Simple Summary SARS-CoV-2 is the virus that causes COVD-19; there is consensus that this virus infects cells presenting the angiotensin-converting enzyme 2 (ACE2) receptor at the cell surface. In our study, we assessed the expression profiles of cancer cells regarding the expressions of ACE2 and furin (another important player in the infection process). We analyzed a series of formalin-fixed paraffin-embedded samples of tumor tissues from cancer patients who underwent surgery at the beginning of the pandemic, including some cases with known positive results for SARS-CoV-2. Our goal was to explore the possibility of viral infections in cancer tissues by detecting viral RNA and/or proteins using histology-based methods. From this extensive methodologic approach, we show that colon and gastric carcinoma cells present high expression levels of ACE2 and furin, contrasting with a negative expression profile of ACE2 in thyroid carcinoma. Some cases tested positive for SARS-CoV-2 by PCR extracted from tissue sections, but in situ hybridization and immunohistochemistry did not show consistent results of a viral presence in the cancer cells. Our study raises the possibility of ACE2-mediated viral tropism for cancer tissues to be clarified in future studies. SARS-CoV-2 pandemics have been massively characterized on a global scale by the rapid generation of in-depth genomic information. The main entry gate of SARS-CoV-2 in human cells is the angiotensin-converting enzyme 2 (ACE2) receptor. The expression of this protein has been reported in several human tissues, suggesting a correlation between SARS-CoV-2 organotropism and ACE2 distribution. In this study, we selected (a series of) 90 patients who were submitted to surgery for tumor removal between the beginning of the SARS-CoV-2 pandemic and the closure of operating rooms (by the end of March 2020) in two different countries-Portugal and Brazil. We evaluated the expressions of ACE2 and furin (another important factor for virus internalization) in colon (n = 60), gastric (n = 19), and thyroid (n = 11) carcinomas. In a subseries of cases with PCR results for SARS-CoV-2 detection in the peri-operatory window (n = 18), we performed different methodological approaches for viral detections in patient tumor samples. Our results show that colon and gastric carcinomas display favorable microenvironments to SARS-CoV-2 tropism, presenting high expression levels of ACE2 and furin. From the subseries of 18 cases, 11 tested positive via PCR detection performed in tumor blocks; however, a direct association between the ACE2 expression and SARS-CoV-2 infection was not demonstrated in cancer cells using histology-based techniques, such as immunohistochemistry or in situ hybridization. This study raises the possibility of ACE2-mediated viral tropism in cancer tissues to be clarified in future studies.

Automated summary

This study evaluated the expression of ACE2 and furin in cancer cells and found that colon and gastric carcinoma cells have high expression levels of ACE2 and furin, while thyroid carcinoma cells do not express ACE2. Although some cases tested positive for SARS-CoV-2 by tissue section PCR, immunohistochemistry and in situ hybridization did not show viral presence in the cancer cells. This study raises the possibility of ACE2-mediated viral tropism in cancer tissues to be clarified in future studies.