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Identification of Lynch syndrome-associated DNA mismatch repair-deficient bladder cancer in a Japanese hospital-based population
Background The prevalence of Lynch syndrome (LS)-associated DNA mismatch repair (MMR)-deficient bladder cancer (BC) has scarcely been investigated. Methods Immunohistochemistry for four MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed in formalin-fixed paraffin-embedded (FFPE) sections prepar...
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Published in: | International journal of clinical oncology 2021-08, Vol.26 (8), p.1524-1532 |
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Main Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Background
The prevalence of Lynch syndrome (LS)-associated DNA mismatch repair (MMR)-deficient bladder cancer (BC) has scarcely been investigated.
Methods
Immunohistochemistry for four MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed in formalin-fixed paraffin-embedded (FFPE) sections prepared from the resected specimens of 618 consecutive newly diagnosed BC cases. Genetic/epigenetic analyses were performed in patients displaying the loss of any MMR proteins in the tumor.
Results
Of the 618 patients, 9 (1.5%) showed the loss of MMR protein expression via immunohistochemistry; specifically, 3, 3, 2, and 1 patients displayed the loss of MLH1/PMS2, PMS2, MSH6, and MSH2/MSH6, respectively. All nine patients were male with a median age of 68 years (63–79 years). One had been previously diagnosed as having LS with an
MSH2
variant. Genetic testing demonstrated the presence of a pathogenic
PMS2
variant (
n
= 1), a variant of uncertain significance in
MSH2
(
n
= 1), and no pathogenic germline variants of the MMR genes (
n
= 1). One patient with MSH6-deficient BC did not complete the genetic testing because of severe degradation of DNA extracted from the FFPE specimen, but the patient was strongly suspected to have LS because of their history of colon cancer and MSH6-deficient upper urinary tract cancer. There remained a possibility that the remaining four patients who refused genetic testing had LS.
Conclusions
The prevalence of LS-associated MMR-deficient BC was estimated to be 0.6–1.1% among unselected BC cases. |
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ISSN: | 1341-9625 1437-7772 |
DOI: | 10.1007/s10147-021-01922-y |