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MMR deficiency is frequent in colorectal carcinomas with diffuse SLFN11 immunostaining: clinicopathologic and molecular study of 31 cases identified among 3,300 tumors

M. Kaczorowski, M. Chłopek, O. Daum, K. Ylaya, T. Vaněček, M. Szczepaniak, K. Krawczyk, A. Kowalik, M. Michal, J. Lasota, M. Miettinen

. 2025 ; 11 (2) : e70025. [pub] -

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25009595

Schlafen 11 (SLFN11), a regulator of cell fate following DNA injury, sensitizes tumor cells to DNA-damaging agents. Patients with SLFN11-positive tumors may benefit from DNA-damaging chemotherapies. SLFN11 has been studied in different types of cancer including colorectal carcinomas. However, colorectal carcinomas with diffuse positivity (expression in ≥80% of tumor cells) have not been meticulously characterized. SLFN11 immunostaining of tumor microarrays (TMAs) with 3,300 primary CRCs identified 65 (~2.0%) tumors with focal staining (<10% of tumor nuclei positive), 83 (~2.5%) with patchy (≥10% and <80%) and 51 (~1.5%) with diffuse (≥80%) SLFN11 positivity. The latter was confirmed on full sections from donor blocks in 31 (~1%) cases, which were further studied including evaluation of additional immunohistochemical markers, genotyping with targeted DNA sequencing, and assessment of microsatellite instability. SLFN11-positive carcinomas were mostly (21/31, 68%) right-sided tumors with a female predominance (21/31, 68%) and median age of 67 years. Eighteen of 31 (58%) contained areas of mucinous differentiation. Deficiency of mismatch repair proteins was detected in 65% (20/31) of SLFN11-positive carcinomas. Moreover, MLH1 (n = 2), MSH2, MSH6, and PMS2 germline mutations were identified in 25% (5/20) of patients with mismatch repair deficient tumors. BRAF p.V600E mutation was found in 45% (9/20) of mismatch repair deficient, but only 1 of 11 proficient tumors. Colorectal carcinomas with diffuse SLFN11 positivity were often mismatch repair deficient tumors with their typical clinical, morphological, and molecular characteristics.

Citace poskytuje Crossref.org

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$a Schlafen 11 (SLFN11), a regulator of cell fate following DNA injury, sensitizes tumor cells to DNA-damaging agents. Patients with SLFN11-positive tumors may benefit from DNA-damaging chemotherapies. SLFN11 has been studied in different types of cancer including colorectal carcinomas. However, colorectal carcinomas with diffuse positivity (expression in ≥80% of tumor cells) have not been meticulously characterized. SLFN11 immunostaining of tumor microarrays (TMAs) with 3,300 primary CRCs identified 65 (~2.0%) tumors with focal staining (<10% of tumor nuclei positive), 83 (~2.5%) with patchy (≥10% and <80%) and 51 (~1.5%) with diffuse (≥80%) SLFN11 positivity. The latter was confirmed on full sections from donor blocks in 31 (~1%) cases, which were further studied including evaluation of additional immunohistochemical markers, genotyping with targeted DNA sequencing, and assessment of microsatellite instability. SLFN11-positive carcinomas were mostly (21/31, 68%) right-sided tumors with a female predominance (21/31, 68%) and median age of 67 years. Eighteen of 31 (58%) contained areas of mucinous differentiation. Deficiency of mismatch repair proteins was detected in 65% (20/31) of SLFN11-positive carcinomas. Moreover, MLH1 (n = 2), MSH2, MSH6, and PMS2 germline mutations were identified in 25% (5/20) of patients with mismatch repair deficient tumors. BRAF p.V600E mutation was found in 45% (9/20) of mismatch repair deficient, but only 1 of 11 proficient tumors. Colorectal carcinomas with diffuse SLFN11 positivity were often mismatch repair deficient tumors with their typical clinical, morphological, and molecular characteristics.
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