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肝细胞性肝癌(HCC)发病率居世界第五位, 因癌死亡原因的第三位, 每年有超过60万病人死于该病[1], 目前HCC在我国死亡率居各种肿瘤死亡率的第二位[2]。随着诊断手段的增加及临床筛选的重视, 发现早期HCC并进行有效的治疗逐步成为可能。而肝活检标本内早期高分化肝细胞肝癌(HDHCC)与异型增生结节(DN)的鉴别诊断一直困扰着病理学界, 尽管肝癌国际合作组织提供了较为详细的组织学诊断标准, 但实际工作中阅片医生的诊断标准的尺度把握参差不齐, 主观性因素常常导致最终诊断的偏差。因此, 在组织形态学基础上探寻能区分两者的相对特异的免疫组织化学(免疫组化)标记或联合标记成为研究热点。本文将探究磷脂酰肌醇蛋白聚糖-3(GPC-3)、CD10、CD147、CD138免疫组化标记在HDHCC与DN中的表达情况, 寻求区分HDHCC与DN的客观诊断依据。
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HE染色示:HDHCC与HD组织形态学非常接近, 鉴别相当困难, 尤其是活检标本更加困难(见图 1)。免疫组化示:HDHCC中GPC-3、CD10、CD147较DN内高表达, 且DN内表达常常杂乱不均(见图 2~5); 而CD138在DN中高表达, HDHCC弱表达或不表达(见图 6)。
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HDHCC和DN内GPC-3、CD10、CD147和CD138的表达差异均有统计学意义(P < 0.01)(见表 1)。
分组 n GPC-3 CD10 CD147 CD138 + - + - + - + - HDHCC 76 66 10 58 18 62 14 27 49 DN 76 31 45 28 48 24 52 44 32 χ2 - 34.90 24.10 38.67 7.64 P - < 0.01 < 0.01 < 0.01 < 0.01 表 1 GPC-3、CD10、CD147和CD138在HDHCC与DN内的表达
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GPC-3、CD10、CD147和CD138联合检测对于HDHCC的敏感度为96.05%(70/76), 特异度为52.63%(见表 2), 说明4种标记物联合检测能明显提高HDHCC的检出率, 但特异度并不高, 需要紧密结合组织形态学改变来区分HDHCC与DN。
指标 灵敏度 特异度 GPC-3+CD10 68(89.47) 48(63.15) GPC-3+CD10+CD147 72(94.73) 43(56.57) GPC-3+CD10+CD147+CD138 73(96.05) 40(52.63) 表 2 GPC-3、CD10、CD147和CD138联合检测的敏感度和特异度[n; 百分率(%)]
GPC-3、CD10、CD147、CD138免疫组织化学联合检测对于高分化肝细胞癌与异型增生的鉴别诊断价值
Differential diagnostic value of the combined immunohistochemistry detection of GPC-3, CD10, CD147 and CD138 in highly differentiated hepatocelluar carcinoma and dysplasia
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摘要:
目的探讨磷脂酰肌醇蛋白聚糖-3(GPC-3)、CD10、CD147和CD138在高分化肝细胞癌与异型增生病理鉴别诊断中的联合互补诊断价值。 方法应用免疫组织化学法检测76例高分化肝细胞癌和癌周异型增生结节内GPC-3、CD10、CD147和CD138的表达情况并进行分析。 结果高分化肝细胞癌组织中GPC-3、CD10、CD147较异型增生结节内高表达,且异型增生结节内表达常常杂乱不均;而CD138在异型增生结节中高表达,高分化肝细胞癌组织中弱表达或不表达。高分化肝细胞癌和异型增生结节组织内GPC-3、CD10、CD147和CD138的表达差异均有统计学意义(P < 0.01)。4种标记联合检测诊断高分化肝细胞癌的灵敏度达96.05%,而特异性仅为52.6%。 结论GPC-3、CD10、CD147和CD138对高分化肝细胞癌与异型增生具有较高的病理鉴别诊断价值,可作为肝穿标本内两者区别的客观辅助指标。 Abstract:ObjectiveTo investigate the differential diagnostic value of the combined immunohistochemistry detection of GPC-3, CD10, CD147 and CD138 in highly differentiated hepatocelluar carcinoma and dysplasia. MethodsThe levels of GPC-3, CD10, CD147 and CD138 in 76 cases with highly differentiated hepatocelluar carcinoma and peripheral dysplastic nodules were explored using immunohistochemistry, and the result of which was analyzed. ResultsCompared with the dysplastic nodules, the levels of GPC-3, CD10 and CD147 in highly differentiated hepatocelluar carcinoma tissue were higher, and these expressions in dysplastic nodules were often disorder and uneven.The expression levels of CD138 in dysplastic nodules and highly differentiated hepatocelluar carcinoma tissue were high and weak or no, respectively.The differences of the levels of GPC-3, CD10, CD147 and CD138 were statistically significant between highly differentiated hepatocelluar carcinoma tissue and dysplastic nodule(P < 0.01).The sensitivities of the combined detection of four markers in highly differentiated hepatocelluar carcinoma tissue and dysplastic nodule were 96.05% and 52.6%, respectively. ConclusionsThe pathologic differential diagnosis value of the combined detection of GPC-3, CD10, CD147 and CD138 in highly differentiated hepatocellular carcinoma and dysplasia is higher, which can be used as the objective auxiliary indicators between the two in liver biopsy specimens. -
Key words:
- hepatocellular carcinoma /
- dysplastic nodule /
- phosphatidylinositol proteoglycan-3 /
- CD147 /
- CD10 /
- CD138 /
- immunohistochemistry
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表 1 GPC-3、CD10、CD147和CD138在HDHCC与DN内的表达
分组 n GPC-3 CD10 CD147 CD138 + - + - + - + - HDHCC 76 66 10 58 18 62 14 27 49 DN 76 31 45 28 48 24 52 44 32 χ2 - 34.90 24.10 38.67 7.64 P - < 0.01 < 0.01 < 0.01 < 0.01 表 2 GPC-3、CD10、CD147和CD138联合检测的敏感度和特异度[n; 百分率(%)]
指标 灵敏度 特异度 GPC-3+CD10 68(89.47) 48(63.15) GPC-3+CD10+CD147 72(94.73) 43(56.57) GPC-3+CD10+CD147+CD138 73(96.05) 40(52.63) -
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