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Journal of Histochemistry and Cytochemistry, Vol. 46, 603-612, May 1998, Copyright © 1998, The Histochemical Society, Inc.

SYMPOSIUM PAPER

Endogenous IL-2 in Cancer Cells: A Marker of Cellular Proliferation

Torsten E. Reicherta, Simon Watkinsc, Joanna Stanson, Jonas T. Johnsonb, and Theresa L. Whitesidea,b
a Departments of Pathology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania
b Otolaryngology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania
c Cell Biology and Physiology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania

Correspondence to: Theresa L. Whiteside, U. of Pittsburgh Cancer Institute, W 1041 Biomedical Science Tower, 211 Lothrop St., Pittsburgh, PA 15213-2582.

We have previously demonstrated that interleukin-2 (IL-2) receptors, IL-2 protein, and mRNA for IL-2 are present in human carcinomas in vitro and in vivo. Carcinoma cells synchronized in the G2/M-phase of the cell cycle express significantly more intracytoplasmic IL-2 as well as IL-2R-ß and -{gamma} than tumor cells in the G0/G1-phase. Here we evaluated immunohistologically the cell cycle-dependent distribution 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 and the data were correlated to the histological grade of the tumors. All tumor cell lines were shown to express IL-2 in the Golgi complex. The strongest IL-2 expression was seen in tumor cells undergoing mitosis, identified by double staining with the antibody to Ki-67. In the tumor tissue, the highest level of co-expression of IL-2 and Ki-67 was observed in poorly differentiated carcinomas, with a labeling index (LI) of 67.2% for IL-2 and 68.8% for Ki-67. Well-differentiated carcinomas showed a significantly lower expression of both proteins (LI 35.0% for IL-2 and 26.5% for Ki-67). The correlation between the labeling indices was statistically significant (r = 0.747; p<0.001). These results demonstrate that IL-2 expression in human carcinoma tissues is strongly associated with cell proliferation and significantly correlates with the histological tumor grade. (J Histochem Cytochem 46:603–611, 1998)

Key Words: , human carcinomas, interleukin-2, cell cycle, Ki-67 antigen, mitosis, tumor grade


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