Expression and Significance of Ki-67 Antigen in Pulmonary Cancer. Relationship between Ki-67 and other Prognostic Factors

摘要

We assessed the proliferative activity in 62 primary pulmonary carcinomas by: determining the percent of Ki-67 immunoreactive cells (stained with MIB-1 antibody), comparing Ki-67 score with the fraction of PCNA positive cells (marked with PC10 antibody) and by evaluating nucleolar organizer regions (NORs) using the histochemical method of staining with coloidal silver and comparing Ki-67 score and the fraction of PCNA positive cells with the mean number of AgNOR per nucleus. We followed the relationship between Ki-67 growth rate, p53 immunoreactivity and the level of epidermal growth factor receptor (EGFR), by staining sections with anti-p53 (DO-7) and anti-EGFR (31G7); tissue sections fixed in formalin and embedded in paraffin were immunohistochemically stained using the Avidin Biotin Complex (ABC) method. The results obtained show: (1) a Ki-67 positivity rate significantly correlated with histological grade (G3) of the tumor (p<0.001; ES) and high cellularity (C3); (2) a statistically insignificant relationship between Ki-67 expression and lymph node involvement (p=0.924448; NS), invasion of pleura and/or thoracic wall (p=0.825267; NS), local relapses (p=0.581481; NS) and distant metastases (p=0.646270; NS); (3) prevalence of p53 positive expression in poorly differentiated pulmonary tumors, with high proliferation rate (p<0.001; ES); (4) an increased level of EGFR expression in highly proliferative tumors, diagnosed in an advanced stage of the disease, which reflects the invasive character and high potential for metastases of Ki-67+ EGFR+ pulmonary carcinomas; (5) a weak correlation between mean of AgNOR per nucleus and IHC markers of proliferative activity. The Ki-67 and PCNA positivity rate, correlated with cellularity of the tumor, together with clinical stage and histological differentiation, offer useful information in anticipating the evolution and prognosis of pulmonary cancer.