Supplemental Digital Content is available in the text. Hepatocellular adenomas (HCAs) often pursue an innocuous clinical course. Recent work has elucidated important subtypes of HCA and biomarkers to identify them, including HCA at an increased risk for malignant transformation. Another key complication of HCAs is the risk of spontaneous tumoral hemorrhage, which may be life-threatening. Identification of a predictive biomarker for this clinical complication would therefore be of clinical value. It has been suggested that Argininosuccinate Synthase 1 (ASS1) immunohistochemistry (IHC) identifies HCA with a high propensity for hemorrhage. The aim of our study was to validate ASS1 IHC as a predictive marker of hemorrhage. Eighty-nine HCAs were collected for ASS1 IHC and subtyped according to published criteria. Clinical records were examined for evidence of tumoral hemorrhage. Twenty-one (23.6%) HCAs were complicated by clinically detected hemorrhage and were more likely to be resected (P=0.0002). Hemorrhage complicated all WHO subtypes of HCA. There was no association between hemorrhage and HCA subtype (P=0.92). Neither the distribution of ASS1 expression nor the intensity of ASS1 expression compared to normal liver showed a significant association with hemorrhage (P=0.051 and 0.34). Interlaboratory comparison of 8 cases showed good agreement regarding the intensity (6/8 and 7/8) and distribution of staining (7/8 and 7/8) across 3 laboratories performing ASS1 IHC. In conclusion, all subtypes of HCA may be complicated by hemorrhage. ASS1 IHC expression did not correlate with hemorrhagic complications. Caution is prudent before routine implementation of ASS1 IHC in clinical practice.

中文翻译：

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精氨琥珀酸合成酶 1 (ASS1) 免疫组织化学是否预测肝细胞腺瘤出血风险增加？

补充数字内容在文本中可用。肝细胞腺瘤 (HCA) 通常是无害的临床过程。最近的工作阐明了 HCA 的重要亚型和用于识别它们的生物标志物，包括恶性转化风险增加的 HCA。HCA 的另一个关键并发症是自发性肿瘤出血的风险，这可能会危及生命。因此，鉴定这种临床并发症的预测性生物标志物将具有临床价值。有人建议精氨琥珀酸合酶 1 (ASS1) 免疫组织化学 (IHC) 鉴定具有高出血倾向的 HCA。我们研究的目的是验证 ASS1 IHC 作为出血的预测标志物。为 ASS1 IHC 收集了 89 个 HCA，并根据公布的标准进行亚型。检查临床记录以寻找肿瘤出血的证据。21 个 (23.6%) HCA 并发临床检测到的出血，更有可能被切除 (P=0.0002)。出血使 HCA 的所有 WHO 亚型复杂化。出血与 HCA 亚型之间没有关联（P=0.92）。与正常肝脏相比，ASS1 表达的分布和 ASS1 表达的强度均未显示出与出血的显着关联（P=0.051 和 0.34）。8 个病例的实验室间比较表明，在 3 个执行 ASS1 IHC 的实验室中，染色强度（6/8 和 7/8）和染色分布（7/8 和 7/8）具有良好的一致性。总之，所有亚型的 HCA 都可能并发出血。ASS1 IHC 表达与出血性并发症无关。