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.

• Keywords
• DNA damaging agents, Lynch syndrome, SLFN11, colorectal cancer, mismatch repair proteins, mucinous carcinoma,
• MeSH
• Adult MeSH
• Nuclear Proteins * metabolism   MeSH
• Carcinoma * metabolism   pathology   MeSH
• Colon * metabolism   pathology   MeSH
• Colorectal Neoplasms * metabolism   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Microsatellite Instability * MeSH
• Biomarkers, Tumor metabolism   MeSH
• DNA Mismatch Repair MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Nuclear Proteins * MeSH
• Biomarkers, Tumor MeSH
• SLFN11 protein, human MeSH Browser