Abstract
Upper tract urothelial carcinoma (UTUC) is the third most common malignancy associated with Lynch syndrome (LS). The current European urology guidelines recommend screening for LS in patients with UTUC up to the age of 60 years. In this study, we examined a cohort of patients with UTUC for potential association with LS in order to establish the sensitivity of current guidelines in detecting LS. A total of 180 patients with confirmed diagnosis of UTUC were enrolled in the study during a 12-year period (2010–2022). Loss of DNA-mismatch repair proteins (MMRp) expression was identified in 15/180 patients (8.3%). Germline analysis was eventually performed in 8 patients confirming LS in 5 patients (2.8%), including 4 germline mutations in MSH6 and 1 germline mutation in MSH2. LS-related UTUC included 3 females and 2 males, with a mean age of 66.2 years (median 71 years, range 46–75 years). Four of five LS patients (all with MSH6 mutation) were older than 65 years (mean age 71.3, median 72 years). Our findings indicate that LS-associated UTUCs can occur in patients with LS older than 60 years. In contrast to previous studies which used mainly highly pre-selected populations with already diagnosed LS, the most frequent mutation in our cohort involved MSH6 gene. All MSH6 mutation carriers were > 65 years, and UTUC was the first LS manifestation in 2/4 patients. Using current screening guidelines, a significant proportion of patients with LS-associated UTUC may be missed. We suggest universal immunohistochemical MMRp screening for all UTUCs, regardless of age and clinical history.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
We acknowledge the National Center for Medical Genomics research infrastructure (LM2018132 funded by MEYS CR) for their support with obtaining scientific data presented in this paper.
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This work was supported by the Cooperation Program, research area SURG, and Institutional Research Fund FN 00669806.
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KP—cases selection, immunohistochemistry evaluation, results interpretation, review of the literature, discussion, manuscript drafting, and final revision; TP—clinical information; RA—results interpretation, manuscript drafting; KB—cases selection; PS—genetic analyses, manuscript drafting; VH—genetic analyses; NP—genetic analyses; IS—genetic analyses, clinical information, manuscript drafting; JS—cases selection, tables preparation; PS—review of the literature and manuscript drafting; MF—review of the literature and manuscript drafting; MS—review of the literature and manuscript drafting; KM—study design; ASP—cases selection, tables; MH—clinical information; MM—study design; OD—study design; MS—study design, manuscript drafting, and final revision; OH—study design, immunohistochemistry, and results evaluation.
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Pivovarcikova, K., Pitra, T., Alaghehbandan, R. et al. Lynch syndrome-associated upper tract urothelial carcinoma frequently occurs in patients older than 60 years: an opportunity to revisit urology clinical guidelines. Virchows Arch 483, 517–526 (2023). https://doi.org/10.1007/s00428-023-03626-2
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DOI: https://doi.org/10.1007/s00428-023-03626-2