title: A comparative assessment of proliferating cell nuclear antigen, c-myc p62, and nucleolar organizer region staining in non-Hodgkin's lymphomas: a histochemical and immunohistochemical study of 200 cases.
abstract: 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.
authors.affiliation: Pathology Department, Asklepeion Hospital, Voula, Athens, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Korkolopoulou
authors.forename: E
authors.initials: E
authors.lastname: Patsouris
authors.forename: G
authors.initials: G
authors.lastname: Pangalis
authors.forename: A
authors.initials: A
authors.lastname: Tsenga
authors.forename: J
authors.initials: J
authors.lastname: Elemenoglou
authors.forename: E
authors.initials: E
authors.lastname: Thomas-Tsangli
authors.forename: D
authors.initials: D
authors.lastname: Spandidos
authors.forename: C
authors.initials: C
authors.lastname: Kittas
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism* / Q000648:ultrastructure*; D009687:Nuclear Proteins / Q000378:metabolism*; D009697:Nucleolus Organizer Region / Q000648:ultrastructure*; D018809:Proliferating Cell Nuclear Antigen; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D013194:Staining and Labeling
chemical_list: D000951:Antigens, Neoplasm; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D016271:Proto-Oncogene Proteins c-myc