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Expression and Prognostic Significance of Kit, Protein Kinase B, and Mitogen-activated Protein Kinase in Patients with Small Cell Lung Cancer¹

Departments of Medical Oncology [F. H. B., N. L., R. F., F. A. S.], Biostatistics [M. P.], and Pathology [M-S. T.], University Health Network-Princess Margaret Hospital and Department of Laboratory Medicine and Pathobiology [M-S. T.], University of Toronto, Toronto, Ontario, M5G 2M5 Canada, and Division of Hematology and Medical Oncology, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia [M. M.]

Purpose: The Kit receptor has been proposed as a key molecular target for the treatment of small cell lung cancer (SCLC). Protein kinase B (PKB/Akt) and mitogen-activated protein kinase (MAPK) are intracellular kinases that regulate cell survival and proliferation and may play a role in Kit signal transduction. This study was designed to examine the expression and importance of Kit, PKB/Akt, and MAPK relative to standard clinical prognostic factors in SCLC.

Experimental Design: Kit, PKB/Akt, and MAPK expression was assessed by immunohistochemistry in SCLC biopsies. Clinical data were collected on tumor stage, weight loss, hematology, biochemistry, response to treatment, and survival. Univariate and multivariate analyses were performed to evaluate prognostic significance.

Results: Biopsies from 42 patients were evaluable, and significant Kit expression (≥35% cells) was detected in 51% of the tumors, phosphorylated PKB/Akt was detected in 62% of the tumors, and phosphorylated MAPK was detected in 48% of the tumors. Neither Kit nor PKB/Akt expression predicted for survival. Only increased expression of cytoplasmic MAPK was prognostic for survival (median, 1 year for negative staining versus 1.8 years for positive staining; P = 0.0054).

Conclusions: Kit, PKB/Akt, and MAPK are expressed in a high percentage of SCLCs, and our data suggest that MAPK is an independent positive predictive factor in this malignancy.

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