Korkolopoulou P, Patsouris E, Pangalis G, Tsenga A, Elemenoglou J, Thomas-Tsangli E, Spandidos D, Kittas C
Pathology Department, Asklepeion Hospital, Voula, Athens, Greece.
Hum Pathol. 1993 Apr;24(4):371-7. doi: 10.1016/0046-8177(93)90084-t.
Proliferating cell nuclear antigen (PCNA) and c-myc p62 oncoprotein are two nuclear proteins expressed in proliferating and transformed cells. They can be recognized immunohistochemically in paraffin sections by the monoclonal antibodies PC-10 and c-myc 1-9E10, respectively. On the other hand, nucleolar organizer regions (NORs) are loops of DNA that carry the r-RNA genes and can be visualized in paraffin sections as black dots (AgNORs) using a silver impregnation method. It has been suggested that the mean number of AgNORs may reflect the cellular kinetics of a tumor. We independently examined 200 cases of non-Hodgkin's lymphomas using the monoclonal antibodies PC-10 and c-myc 1-9E10, as well as the AgNOR method. Our study shows a very significant correlation between PCNA, c-myc expression, and AgNOR count on the one hand and histologic grade on the other (P < .001), although a significant overlap among the three grades exists. PC-10, c-myc 1-9E10, and AgNOR scores are all shown to be linearly related, even though significant discrepancies were observed, and the correlation is stronger between PCNA and AgNORs (PCNA v c-myc p62, r = .551; PCNA v AgNORs, r = .746; c-myc p62 v AgNORs, r = .529; P < .001). A remarkable finding is that the intermediate group of lymphomas is heterogeneous as far as the proliferative rate is concerned: diffuse large cell cleaved/non-cleaved lymphomas (category G of the Working Formulation) are characterized by a significantly higher proliferative index, as evidenced by the elevated PCNA, c-myc p62, and AgNOR scores, in comparison with the other types of intermediate-grade lymphomas (P < .001). However, the proliferative rate is lower than that of the high-grade lymphomas (PCNA, P < .05; c-myc p62, P < .001; AgNORs, P < .005). No significant difference exists between B-cell and T-cell lymphomas except for the higher expression of c-myc p62 in intermediate-grade B-cell lymphomas, obviously due to the higher proliferative rate of diffuse large cell lymphomas. Based on our findings, it appears that the combination of PCNA, c-myc p62, and AgNORs provides an accurate estimate of the proliferative rate of non-Hodgkin's lymphomas in paraffin sections. Clinical studies may show whether this information has prognostic value independent of histologic classification. In addition, our results suggest that category G (diffuse large cell) lymphomas may belong to a malignancy grade higher than the intermediate grade, a suggestion consistent with their more aggressive biologic behavior.
增殖细胞核抗原（PCNA）和c-myc p62癌蛋白是在增殖细胞和转化细胞中表达的两种核蛋白。它们可以分别通过单克隆抗体PC-10和c-myc 1-9E10在石蜡切片中进行免疫组织化学识别。另一方面，核仁组织区（NORs）是携带r-RNA基因的DNA环，使用银浸染法在石蜡切片中可将其可视化为黑点（AgNORs）。有人提出AgNORs的平均数可能反映肿瘤的细胞动力学。我们使用单克隆抗体PC-10和c-myc 1-9E10以及AgNOR方法独立检测了200例非霍奇金淋巴瘤。我们的研究表明，一方面PCNA、c-myc表达和AgNOR计数与另一方面的组织学分级之间存在非常显著的相关性（P <.001），尽管三个分级之间存在显著重叠。PC-10、c-myc 1-9E10和AgNOR评分均显示呈线性相关，尽管观察到显著差异，且PCNA与AgNORs之间的相关性更强（PCNA与c-myc p62，r =.551；PCNA与AgNORs，r =.746；c-myc p62与AgNORs，r =.529；P <.001）。一个显著的发现是，就增殖率而言，淋巴瘤的中间组是异质性的：弥漫性大细胞裂/未裂淋巴瘤（工作分类法的G类）的特征是增殖指数显著更高，PCNA、c-myc p62和AgNOR评分升高证明了这一点，与其他类型的中间级淋巴瘤相比（P <.001）。然而，其增殖率低于高级别淋巴瘤（PCNA，P <.05；c-myc p62，P <.001；AgNORs，P <.005）。B细胞和T细胞淋巴瘤之间除了中间级B细胞淋巴瘤中c-myc p62表达较高外，没有显著差异，这显然是由于弥漫性大细胞淋巴瘤的增殖率较高。基于我们的发现，PCNA、c-myc p62和AgNORs的组合似乎可以准确估计石蜡切片中非霍奇金淋巴瘤的增殖率。临床研究可能会表明该信息是否具有独立于组织学分类的预后价值。此外，我们的结果表明G类（弥漫性大细胞）淋巴瘤可能属于比中间级更高的恶性等级，这一观点与其更具侵袭性的生物学行为一致。
