联合使用热休克蛋白70和谷氨酰胺合成酶有助于鉴别典型肝细胞腺瘤与非典型肝细胞肿瘤以及高分化肝细胞癌。
Combined use of heat-shock protein 70 and glutamine synthetase is useful in the distinction of typical hepatocellular adenoma from atypical hepatocellular neoplasms and well-differentiated hepatocellular carcinoma.
作者信息
Nguyen Thuy B, Roncalli Massimo, Di Tommaso Luca, Kakar Sanjay
机构信息
Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
Department of Pathology, Mills Peninsula Medical Group, South San Francisco, CA, USA.
出版信息
Mod Pathol. 2016 Mar;29(3):283-92. doi: 10.1038/modpathol.2015.162. Epub 2016 Jan 15.
Well-differentiated hepatocellular carcinoma can mimic high-grade dysplastic nodule in cirrhotic liver and hepatocellular adenoma in non-cirrhotic liver. This study evaluates the efficacy of combined use of heat-shock protein 70 (HSP70), glutamine synthetase (GS) and glypican-3 in this setting. Immunohistochemistry for these three markers was done in 17 typical hepatocellular adenoma, 15 high-grade dysplastic nodules, 20 atypical hepatocellular neoplasms (14 clinically atypical and 6 pathologically atypical), 14 very well-differentiated hepatocellular carcinoma, and 43 well-differentiated hepatocellular carcinoma. All three markers were negative in typical adenomas. HSP70 was positive in 10, 71, and 67% of atypical neoplasms, very well-differentiated and well-differentiated HCC, respectively, while GS was positive in 60, 50, and 60% of atypical neoplasms, very well-differentiated and well-differentiated hepatocellular carcinoma, respectively. Glypican-3 was negative in all atypical neoplasms and very well-differentiated hepatocellular carcinoma, and was positive in 27% of well-differentiated hepatocellular carcinoma. Positive staining with at least one marker (HSP70 and/or GS) was seen in 85% of very well-differentiated hepatocellular carcinoma, which was similar to well-differentiated hepatocellular carcinoma (78%, P=0.4), and pathologically atypical cases (100%, P=0.5), but significantly higher compared with clinically atypical cases (43%. P=0.03) and none of typical adenomas (P<0.001). Positive staining with both GS and HSP70 was seen significantly more often in hepatocellular carcinoma compared with atypical neoplasms (45 vs 10%, P=0.004). Both these markers were also more often expressed in very well-differentiated hepatocellular carcinoma compared with atypical cases (38 vs 10%, P=0.06). In conclusion, the combined use of GS and HSP70 can be useful in the diagnosis of very well-differentiated hepatocellular carcinoma. These stains can also help in the distinction of typical adenoma from atypical hepatocellular neoplasms. Glypican-3 has low sensitivity and is not useful in this setting.
高分化肝细胞癌可在肝硬化肝脏中模拟高级别发育异常结节，在非肝硬化肝脏中模拟肝细胞腺瘤。本研究评估了热休克蛋白70（HSP70）、谷氨酰胺合成酶（GS）和磷脂酰肌醇蛋白聚糖-3联合应用在这种情况下的效果。对17例典型肝细胞腺瘤、15例高级别发育异常结节、20例非典型肝细胞肿瘤（14例临床非典型和6例病理非典型）、14例高分化肝细胞癌和43例高分化肝细胞癌进行了这三种标志物的免疫组化检测。所有三种标志物在典型腺瘤中均为阴性。HSP70在非典型肿瘤、高分化和高分化肝癌中的阳性率分别为10%、71%和67%，而GS在非典型肿瘤、高分化和高分化肝细胞癌中的阳性率分别为60%、50%和60%。磷脂酰肌醇蛋白聚糖-3在所有非典型肿瘤和高分化肝细胞癌中均为阴性，在27%的高分化肝细胞癌中为阳性。在85%的高分化肝细胞癌中可见至少一种标志物（HSP70和/或GS）呈阳性染色，这与高分化肝细胞癌（78%，P = 0.4）和病理非典型病例（100%，P = 0.5）相似，但与临床非典型病例（43%，P = 0.03）相比显著更高，且在所有典型腺瘤中均无阳性染色（P < 0.001）。与非典型肿瘤相比，GS和HSP70双阳性染色在肝细胞癌中出现的频率显著更高（45%对10%，P = 0.004）。与非典型病例相比，这两种标志物在高分化肝细胞癌中也更常表达（38%对10%，P = 0.06）。总之，GS和HSP70联合应用有助于高分化肝细胞癌的诊断。这些染色也有助于区分典型腺瘤和非典型肝细胞肿瘤。磷脂酰肌醇蛋白聚糖-3敏感性低，在此情况下无用。
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