High homogeneity of mismatch repair deficiency in advanced prostate cancer
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High homogeneity of mismatch repair deficiency in advanced prostate cancer. / Fraune, Christoph; Simon, Ronald; Höflmayer, Doris; Möller, Katharina; Dum, David; Büscheck, Franziska; Hube-Magg, Claudia; Makrypidi-Fraune, Georgia; Kluth, Martina; Hinsch, Andrea; Burandt, Eike; Clauditz, Till Sebastian; Wilczak, Waldemar; Sauter, Guido; Steurer, Stefan.
In: VIRCHOWS ARCH, Vol. 476, No. 5, 05.2020, p. 745-752.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - High homogeneity of mismatch repair deficiency in advanced prostate cancer
AU - Fraune, Christoph
AU - Simon, Ronald
AU - Höflmayer, Doris
AU - Möller, Katharina
AU - Dum, David
AU - Büscheck, Franziska
AU - Hube-Magg, Claudia
AU - Makrypidi-Fraune, Georgia
AU - Kluth, Martina
AU - Hinsch, Andrea
AU - Burandt, Eike
AU - Clauditz, Till Sebastian
AU - Wilczak, Waldemar
AU - Sauter, Guido
AU - Steurer, Stefan
PY - 2020/5
Y1 - 2020/5
N2 - 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.
AB - 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.
U2 - 10.1007/s00428-019-02701-x
DO - 10.1007/s00428-019-02701-x
M3 - SCORING: Journal article
C2 - 31811435
VL - 476
SP - 745
EP - 752
JO - VIRCHOWS ARCH
JF - VIRCHOWS ARCH
SN - 0945-6317
IS - 5
ER -