ENDOGENOUS IL-2 IN CANCER-CELLS - A MARKER OF CELLULAR PROLIFERATION

We have previously demonstrated that interleukin-2 (IL-2) receptors, I L-2 protein, and mRNA for IL-2 are present in human carcinomas in vitr o and in vivo. Carcinoma cells synchronized in the G(2)/M-phase of the cell cycle express significantly more intracytoplasmic IL-2 as well a s IL-2R-beta and -gamma than tumor cells in the G(0)/G(1)-phase. Here we evaluated immunohistologically the cell cycle-dependent distributio n of the proliferation-associated Ki-67 antigen and expression of the cytokine IL-2 in four different carcinoma cell lines. In addition, 34 tissue samples from patients with squamous cell carcinomas of the head and neck were simultaneously analyzed for Ki-67 and IL-2 expression a nd the data were correlated to the histological grade of the tumors. A ll tumor cell lines were shown to express IL-2 in the Golgi complex. T he strongest IL-2 expression was seen in tumor cells undergoing mitosi s, identified by double staining with the antibody to Ki-67. In the tu mor tissue, the highest level of co-expression of IL-2 and Ki-67 was o bserved in poorly differentiated carcinomas, with a labeling index (LI ) of 67.2% for IL-2 and 68.8% for Ki-67. Well-differentiated carcinoma s showed a significantly lower expression of both proteins (LI 35.0% f or IL-2 and 26.5% for Ki-67). The correlation between the labeling ind ices was statistically significant (r = 0.747; p<0.001). These results demonstrate that IL-2 expression in human carcinoma tissues is strong ly associated with cell proliferation and significantly correlates wit h the histological tumor grade.