Ojanguren I, Ariza A, Llatjós M, Castellà E, Mate J L, Navas-Palacios J J
Department of Anatomic Pathology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
Hum Pathol. 1993 Aug;24(8):905-8. doi: 10.1016/0046-8177(93)90141-3.
Information about a tissue's proliferative activity can be obtained from the immunocytochemical investigation of proliferating cell nuclear antigen (PCNA), an auxiliary protein of DNA polymerase delta expressed by cycling cells. To determine whether a relationship exists between morphology and PCNA expression in normal, regenerative, and malignant neoplastic hepatocytes, this study was undertaken on 48 fine-needle aspiration cytology (FNAC) cell blocks from eight normal livers, eight cirrhotic livers, and 32 hepatocellular carcinomas (HCCs), as well as on 41 needle or wedge biopsy specimens from 10 normal livers, 13 cirrhotic livers, one focal nodular hyperplastic liver, and 17 HCCs. Anti-PCNA monoclonal antibody PC10 was applied to formalin-fixed, paraffin-embedded tissue using the avidin-biotin method. Proliferating cell nuclear antigen immunoreactivity was evaluated as follows: absent; minimal, less than 5% positive nuclei; grade 1, 5% to 25% positive nuclei; grade 2, 26% to 50% positive nuclei; grade 3, 51% to 75% positive nuclei; and grade 4, 76% to 100% positive nuclei. In both the FNAC and biopsy series normal and regenerative livers were either completely negative or minimally immunoreactive (under 5% positive nuclei). In contrast, all well-differentiated HCC cases exhibited over 15% positive nuclei. Most well-differentiated HCCs were grade 1 (85.7% in the FNAC series and 76.92% in the biopsy series) and the majority of moderately differentiated HCCs were grade 3 (63.63% in the FNAC series, but only 50% in the biopsy series). Therefore, absent or minimal PCNA immunoreactivity seems to be a useful adjuvant to discriminate normal/regenerative liver from HCC, whose degree of differentiation tends to correlate with the level of PCNA expression. These observations apply to both the FNAC and biopsy series, which yielded very similar data.
关于组织增殖活性的信息可通过对增殖细胞核抗原（PCNA）进行免疫细胞化学研究获得，PCNA是一种由处于细胞周期的细胞表达的DNA聚合酶δ辅助蛋白。为了确定正常、再生和恶性肿瘤性肝细胞的形态与PCNA表达之间是否存在关联，本研究对来自8个正常肝脏、8个肝硬化肝脏和32个肝细胞癌（HCC）的48个细针穿刺细胞学（FNAC）细胞块，以及来自10个正常肝脏、13个肝硬化肝脏、1个局灶性结节性增生肝脏和17个HCC的41个针吸或楔形活检标本进行了研究。使用抗生物素蛋白-生物素方法将抗PCNA单克隆抗体PC10应用于福尔马林固定、石蜡包埋的组织。增殖细胞核抗原免疫反应性评估如下：无；最低，阳性细胞核少于5%；1级，阳性细胞核为5%至25%；2级，阳性细胞核为26%至50%；3级，阳性细胞核为51%至75%；4级，阳性细胞核为76%至100%。在FNAC和活检系列中，正常和再生肝脏要么完全阴性，要么免疫反应性最低（阳性细胞核低于5%）。相比之下，所有高分化HCC病例的阳性细胞核均超过15%。大多数高分化HCC为1级（FNAC系列中为85.7%，活检系列中为76.92%），大多数中分化HCC为3级（FNAC系列中为63.63%，但活检系列中仅为50%）。因此，PCNA免疫反应性缺失或最低似乎是区分正常/再生肝脏与HCC的有用辅助手段，HCC的分化程度往往与PCNA表达水平相关。这些观察结果适用于FNAC和活检系列，二者得出的数据非常相似。
