Supplementary Material for: IMMUNOHISTOCHEMISTRY, MOLECULAR BIOLOGY AND CLINICAL SCORING FOR THE DETECTION OF MUIR-TORRE SYNDROME IN CUTANEOUS SEBACEOUS TUMORS: WHICH STRATEGY?

Background
Sebaceous neoplasms (SNs) always raise the possibility of an association with Muir-Torre syndrome (MTS) and permit to screen internal malignancies, colorectal and endometrial carcinomas, before they become symptomatic. Immunohistochemistry (IHC), molecular biology and clinical examination are different approaches for detection of MTS. We conducted a retrospective analysis of non-selected SNs in order to determine the optimal tools to implement for MTS screening.
Methods
Deficient MMR phenotype (dMMR) was determined by either IHC using antibodies directed to four mismatch repair (MMR) antigens on tissue-microarray or molecular biology using pentaplex PCR. The Mayo-Clinic-Risk score of MTS was calculated from medical records. Sensibility and specificity of each test for the detection of MTS was determined.
Results
We included 107 patients, 8 with multiple SNs, for a total of 123 SNs (43 sebaceous adenomas, 19 sebaceomas and 61 sebaceous carcinomas (SC)). Loss of at least one MMR protein was observed in 70.7% of tumors while 48% had a microsatellite instable phenotype. Concordance between both techniques was 92.9%, with a 0.85 Cohen’s kappa coefficient. Nineteen patients (20.2%) had a ≥2 points Mayo-Clinic-Risk-Score, one having a pMMR SC. Among the 13 patients with confirmed MTS, 2 had a low Mayo-Clinic-risk score (1 point). IHC had the highest sensitivity for MTS screening (100%) with a specificity of 34.1% while a >2 points Mayo-Clinic-Risk-Score had a lower sensitivity (92%) but a higher specificity (89%).
Conclusion
To detect MTS in SNs patients, first line Mayo-Clinic-risk-score followed by IHC appears the most accurate strategy with lower cost for society. This strategy should be adapted to the medico-economic resources of each country.

背景
皮脂腺肿瘤（SNs）始终伴随着与Muir-Torre综合征（MTS）关联的可能性，并允许在肿瘤出现症状之前对内部恶性肿瘤、结直肠癌和子宫内膜癌进行筛查。免疫组化（IHC）、分子生物学和临床检查是检测MTS的不同方法。本研究通过对非选择性SNs进行回顾性分析，旨在确定实施MTS筛查的最佳工具。
方法
通过组织微阵列上针对四个错配修复（MMR）抗原的抗体进行IHC或通过五重PCR进行分子生物学来确定缺陷MMR表型（dMMR）。从病历中计算MTS的Mayo-Clinic-Risk评分。确定每种检测方法检测MTS的灵敏度和特异性。
结果
我们纳入了107名患者，其中8名患者有多发性SNs，总计123个SNs（43个皮脂腺腺瘤、19个皮脂腺瘤和61个皮脂腺癌（SC））。在70.7%的肿瘤中观察到至少一种MMR蛋白的丢失，其中48%具有微卫星不稳定性表型。两种技术之间的一致性为92.9%，Cohen's kappa系数为0.85。19名患者（20.2%）具有≥2点的Mayo-Clinic-Risk-Score，其中1名患者有pMMR SC。在13名确诊为MTS的患者中，2名患者具有较低的Mayo-Clinic风险评分（1分）。IHC在MTS筛查中具有最高的灵敏度（100%），特异性为34.1%，而≥2点的Mayo-Clinic-Risk-Score具有较低的灵敏度（92%）但较高的特异性（89%）。
结论
为了检测SNs患者的MTS，首选Mayo-Clinic风险评分，随后是IHC，这似乎是最准确且对社会责任成本较低的战略。该战略应根据各国的医经济资源进行调整。