We studied argyrophilic proteins associated with nucleolar organizer regions (AgNOR) in non-small-cell cancer. We determined the area index (AI) and coefficient of variation (CV) of AgNOR. AI is associated with the key clinicomorphological parameters within the TNM system: and values, greatest tumor dimension up to 3？cm and more, disease stage, histogenesis, and tumor differentiation. CV is associated with value, greatest tumor dimension up to 3？cm and more, histogenesis, and tumor differentiation. Survival of patients is longer in low AI or CV values versus high AI or CV values, longer in low AI and CV values (？AI/？CV type), shorter in high AI and CV values (+AI/+CV type), and intermediate in opposite AI and CV values (？AI/+CV and +AI/？CV types). Independent predictors in non-small-cell lung cancer include value, greatest tumor dimension, histogenesis, and CV. Assessment of quantitative values and heterogeneity of AgNOR is important for differential diagnosis and prognosis of non-small-cell lung cancer. 1. Introduction Lung cancer is a prevailing malignancy, with 80% of cases being non-small-cell cancer. Long-term treatment outcomes and survival of patients with non-small-cell cancer leave much to be desired. Therefore it is important to study morphological criteria related to the key clinicomorphological parameters of tumor and non-small-cell lung cancer patient survival and more accurate ways of predicting the course of the disease [1]. Currently evaluation of argyrophilic proteins associated with nucleolar organizer regions (AgNOR) is a generally established marker of proliferative activity and the cell cycle rate. Up to 75% of AgNOR staining is made by the two argyrophilic proteins: C23 (nucleolin) and B23 (nucleophosmin), playing a key role in ribosomal RNA synthesis. These proteins are detected in cell nuclei for the whole duration of the cell cycle, with a 1.5–3-fold increase occurring during S- and G2-phases [2]. Inverse relationship between quantitative amount of AgNOR and the cell cycle duration [3], doubling time of the tumor cell mass [4, 5], has been shown. In histopathologic practice for the purpose of objectivization and standardization of AgNOR protein evaluation it was proposed to use special software for image analysis and internal staining control [6–9]. Due to heterogeneity of cell populations within one tumor it was proposed to assess variability of AgNOR in tumor cells (coefficient of variation, CV), apart from AgNOR assay [10]. Literature analysis has shown controversy of association of AgNOR with clinicomorphological parameters
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