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.

联合运用热休克蛋白70和谷氨酰胺合成酶有助于区分典型肝细胞腺瘤、非典型肝细胞肿瘤及高分化肝细胞癌

Nguyen TB,Roncalli M,Di Tommaso L,Kakar S

阅读：971 Modern Pathology； Mar 2016; 29 (3): 210 - 314:283-92

Abstract

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.

摘要

高分化肝细胞癌类似硬化性肝中的高级别异型增生结节和非硬化性肝中的肝细胞腺瘤。本研究评估上述情况下联合运用热休克蛋白70（HSP70）、谷氨酰胺合成酶（GS）和glypican-3的鉴别效用。

免疫组化检测17例典型肝细胞腺瘤，15例高级别异型增生结节，20例非典型肝细胞肿瘤（14例临床非典型和6例病理学非典型），14例超高分化肝细胞癌和43例高分化肝细胞癌中这三种标记物的表达。典型腺瘤中所有三种标记物阴性。非典型肿瘤、超高分化和高分化HCC中HSP70阳性病例分别为10%、71%和67%，而GS阳性病例分别为60%、50%和60%。所有非典型肿瘤和超高分化肝细胞癌中glypican-3阴性，高分化肝细胞癌中27%阳性。至少一种标记物（HSP70和/或GS）阳性染色见于85%超高分化肝细胞癌，与高分化肝细胞癌（78%，p=0.4）和病理学非典型病例相似（100%，p=0.5），但显著高于临床非典型病例（43%，p=0.03）及无表达的典型腺瘤（p＜0.001）。与非典型肿瘤相比，GS和HSP70双阳性染色更多见于肝细胞癌（45 %vs 10%，p=0.004）。这两种标记物也更常表达于超高分化肝细胞癌，而不是非典型病例（38% vs 10%，p=0.06）。

总之，联合运用GS和HSP70有助于诊断超高分化肝细胞癌。这些染色也能帮助区分典型腺瘤和非典型肝细胞肿瘤。Glypican-3敏感性低，上述情况使用没有帮助。