BACKGROUND: Recent reports have described favorable response rates for immune checkpoint inhibitors in prostate cancers with microsatellite instability (MSI). However, it is unclear whether MSI affects the entire tumor mass or is distributed heterogeneously, the latter potentially impairing treatment efficiency. METHODS: To identify prostate cancers with MSI, 316 advanced prostate cancers were analyzed by immunohistochemistry (IHC) for the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6 on a TMA format. RESULTS: Out of 200 interpretable cancers, IHC findings were consistent with MSI in 10 tumors. In 9 of these 10 cancers, tissue blocks were available for subsequent large section IHC, confirming MSI in 6 cases, each with combined protein loss of MSH2 and MSH6. One additional tumor with unequivocal loss of MLH1 and PMS2 on the TMA, for which further analyses could not be carried out due to lack of tissue, was also considered to exhibit MSI. In total, 7 of 200 interpretable advanced prostate cancers were found to exhibit MMR deficiency/MSI (3.5%). Subsequent analysis of all available cancer-containing archived tissue blocks (n=114) revealed consistent and homogeneous MMR protein loss in each case. Polymerase chain reaction (PCR)-based analysis using the "Bethesda panel" could be executed in 6 MMR deficient tumors of which 4 were MSI-high and 2 were MSI-low. CONCLUSIONS: The absence of intratumoral heterogeneity for the MMR status suggests that MSI occurs early in prostate cancer. It is concluded that MMR analysis on limited biopsy material by IHC is sufficient to estimate the MMR status of the entire cancer mass.
BACKGROUND: Recent reports have described favorable response rates for immune checkpoint inhibitors in prostate cancers with microsatellite instability (MSI). However, it is unclear whether MSI affects the entire tumor mass or is distributed heterogeneously, the latter potentially impairing treatment efficiency. METHODS: To identify prostate cancers with MSI, 316 advanced prostate cancers were analyzed by immunohistochemistry (IHC) for the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6 on a TMA format. RESULTS: Out of 200 interpretable cancers, IHC findings were consistent with MSI in 10 tumors. In 9 of these 10 cancers, tissue blocks were available for subsequent large section IHC, confirming MSI in 6 cases, each with combined protein loss of MSH2 and MSH6. One additional tumor with unequivocal loss of MLH1 and PMS2 on the TMA, for which further analyses could not be carried out due to lack of tissue, was also considered to exhibit MSI. In total, 7 of 200 interpretable advanced prostate cancers were found to exhibit MMR deficiency/MSI (3.5%). Subsequent analysis of all available cancer-containing archived tissue blocks (n=114) revealed consistent and homogeneous MMR protein loss in each case. Polymerase chain reaction (PCR)-based analysis using the "Bethesda panel" could be executed in 6 MMR deficient tumors of which 4 were MSI-high and 2 were MSI-low. CONCLUSIONS: The absence of intratumoral heterogeneity for the MMR status suggests that MSI occurs early in prostate cancer. It is concluded that MMR analysis on limited biopsy material by IHC is sufficient to estimate the MMR status of the entire cancer mass.
Authors: David Dum; Stefan Steurer; Ronald Simon; Pia Victoria Zimmermann; Eike Burandt; Till Sebastian Clauditz; Margit Fisch; Michael Rink; Roland Dahlem; Wolfgang Höppner; Henrik Zecha; Ousman Doh; Cord Matthies; Waldemar Wilczak; Guido Sauter; Christoph Fraune Journal: Transl Androl Urol Date: 2021-03
Authors: Christoph Fraune; Eike Burandt; Ronald Simon; Claudia Hube-Magg; Georgia Makrypidi-Fraune; Martina Kluth; Franziska Büscheck; Doris Höflmayer; Niclas Ch Blessin; Tim Mandelkow; Wenchao Li; Daniel Perez; Jakob R Izbicki; Waldemar Wilczak; Guido Sauter; Jörg Schrader; Michael Neipp; Hamid Mofid; Thies Daniels; Christoph Isbert; Till S Clauditz; Stefan Steurer Journal: Ann Surg Oncol Date: 2020-02-27 Impact factor: 4.339