Increased expression of Id family proteins in small cell lung cancer and its prognostic significance

Purpose: To study the molecular pathology of human small cell lung cancer (SCLC), molecular biology approaches were used to identify genes involved in malignant progression of the cancer cells. Experimental Design: Microquantity differential display was used initially to identify genes expressed differentially between normal and malignant cell lines. The differences were verified by Western blot. Immunohistochemical analysis was done on paired normal and malignant lung tissues and on tissues taken by biopsy to assess the expression status of candidate genes and their prognostic significance. Results: Inhibitor of DNA/differentiation (Id)1 gene was up-regulated in SCLC cells. Levels of Id1 in 8 of 10 cell lines were increased by 1.7- to 21.4-fold when compared with the benign cells. A similar increase was also found in levels of Id2 and Id3. On 26 pairs of lung tissues, all four Id proteins were significantly (Wilcoxon Signed RankTest, P < 0.001-0.005) overexpressed in cytoplasm of the malignant cells. In nuclei of SCLC cells, Id1 expression was significantly reduced, whereas the levels of Id2, Id3, and Id4 were significantly (Wilcoxon Signed Rank Test, P < 0.001) increased. Immunohistochemical staining on biopsy specimens showed that the increased expression of Id2 in cytoplasm of cancer cells, not the other three proteins, was significantly associated with the increased survival of SCLC patients. Conclusion: Changed expression profiles of Id proteins may play important roles in malignant progression of SCLC, and the increased Id2 in cytoplasm is a novel prognostic factor to predict the patient outcomes.