Te. Reichert et al., ENDOGENOUS IL-2 IN CANCER-CELLS - A MARKER OF CELLULAR PROLIFERATION, The Journal of histochemistry and cytochemistry, 46(5), 1998, pp. 603-611
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.