Cutaneous Biology Lab, Institut Cochin, INSERM U1016, UMR 8104, Paris, France; Department of Dermatology, Hôpital Cochin, AP-HP Centre-Université Paris Cité, Paris, France; Faculté de Médecine Paris Centre Santé, University Paris Cité, Paris, France.
Department of Pathology, Hôpital Bichat, AP-HP Nord-Université Paris Cité, Paris, France; CARADERM, French Network of Rare Cutaneous Cancers, Lille, France.
Mod Pathol. 2023 Apr;36(4):100101. doi: 10.1016/j.modpat.2023.100101. Epub 2023 Jan 18.
The accurate diagnosis of skin adnexal neoplasms is sometimes challenging but is necessary because medical management and follow-up may differ between tumors. GATA6 transcription factor has been identified as a new marker of the upper folliculosebaceous compartment (lower infundibulum, junctional zone and isthmus, and upper sebaceous gland) in the human skin. We aimed to determine the diagnostic accuracy of GATA6 immunostaining to diagnose sebaceous tumors compared with that to diagnose other adnexal and nonadnexal cutaneous neoplasms. We conducted a retrospective, evaluator-nonblinded study comparing the reference standard (diagnosis by an expert dermatopathologist) with GATA6 immunostaining to identify sebaceous tumors in a cohort containing 234 different tumors. The GATA6 expression score was significatively higher in sebaceous than that in nonsebaceous tumors. In addition, tumors originating from the upper hair follicle showed positive results for GATA6 staining; however, they showed lower GATA6 expression scores. Detection of sebaceous tumors using GATA6 positivity had a sensitivity of 95.7% (95% CI, 85.8-99.2), specificity of 80.8% (95% CI, 74.5-85.8), positive predictive value of 55.6% (95% CI, 44.7-65.9), and negative predictive value of 98.7% (95% CI, 95.4-99.8). GATA6 showed similar sensitivity to adipophilin, the reference marker; however, the specificity of GATA6 was higher, as observed in a cohort of 106 tumors enriched in squamous cell carcinomas with clear-cell histology. In addition, GATA6 positivity was assessed in 39 sebaceous carcinomas and compared with epithelial membrane antigen (EMA), CK7, and androgen receptor (AR) staining results. Although CK7 staining displayed lower diagnostic performances, GATA6 staining showed comparable results as EMA and AR. Finally, we found GATA6 expression in skin metastases of gastrointestinal origin, whereas GATA6 was absent in metastases originating from breast or lung cancers. Overall, our work identified GATA6 immunostaining as a new diagnostic tool for sebaceous tumors.
皮肤附属器肿瘤的准确诊断有时具有挑战性,但这是必要的,因为肿瘤的医疗管理和随访可能不同。GATA6 转录因子已被确定为人类皮肤中上滤泡-皮脂腺隔(下部漏斗、连接区和峡部以及上部皮脂腺)的新标志物。我们旨在确定 GATA6 免疫染色诊断皮脂腺肿瘤的诊断准确性,与诊断其他附属器和非附属器皮肤肿瘤的准确性进行比较。我们进行了一项回顾性、评估者非盲研究,将参考标准(由一位皮肤科专家病理学家诊断)与 GATA6 免疫染色进行比较,以确定包含 234 种不同肿瘤的队列中的皮脂腺肿瘤。与非皮脂腺肿瘤相比,GATA6 在皮脂腺肿瘤中的表达评分显着更高。此外,来源于上毛囊的肿瘤对 GATA6 染色呈阳性反应;然而,它们的 GATA6 表达评分较低。使用 GATA6 阳性检测到的皮脂腺肿瘤的敏感性为 95.7%(95%置信区间,85.8-99.2),特异性为 80.8%(95%置信区间,74.5-85.8),阳性预测值为 55.6%(95%置信区间,44.7-65.9),阴性预测值为 98.7%(95%置信区间,95.4-99.8)。GATA6 的敏感性与脂肪细胞分化抗原( adipophilin)相似,后者是参考标志物;然而,GATA6 的特异性更高,在富含具有透明细胞组织学的鳞状细胞癌的 106 例肿瘤队列中观察到这种情况。此外,在 39 例皮脂腺癌中评估了 GATA6 阳性,并将其与上皮膜抗原(EMA)、CK7 和雄激素受体(AR)染色结果进行比较。尽管 CK7 染色显示出较低的诊断性能,但 GATA6 染色显示出与 EMA 和 AR 相当的结果。最后,我们在胃肠道来源的皮肤转移中发现了 GATA6 的表达,而在源自乳腺癌或肺癌的转移中则没有发现 GATA6。总的来说,我们的工作确定了 GATA6 免疫染色作为一种新的皮脂腺肿瘤诊断工具。