Acetylation and methylation of lysine residues in the tails of nucleosomal core histones has a crucial role in chromatin packing and gene expression. It is assumed that global histone modification pattern is associated with epigenetic setting of gene expression pattern and biology of the cell. A recent study revealed that global histone modification patterns of prostatic cancer predict risk of disease recurrence. Here we evaluated global modification status of lysine residues of histone H3 and H4 in 408 non small cell lung cancer (NSCLC) tissues by using immunohistochemical staining against acetylated (Ac) H3K9 and H4K16, and of trimethylated (TriMe) H3K9 and H4K20. Normal alveolar and bronchial epithelial cells and lymphoid cells showed strong staining to H3K9TriMe and H4K20TriMe, in contrast to NSCLC which showed variable staining scores for each antibody. In clinicopathological analyses, staining scores of four different antibodies were not correlated with histologic subtype, tumor differentiation, size and stage. Interestingly, the strong expression of H3K9Ac (p=0.001), H3K9TriMe (p=0.002), and H4K16Ac (p<0.001) were correlated with the less tumor recurrence, whereas the absence or weak expression of H4K20 TriMe were correlated with the less tumor recurrence (p=0.041). Additionally, we clustered the patients according to histone modification patterns; acetylation dominant versus methylation dominant groups of H3 and H4. Seventy three percent (298/408) were classified into H4 acetylation dominant group and showed higher stage (p=0.025) and more frequent distant metastasis (p=0.040). However, 176 (43.1%) were classified into H3 acetylation dominant group and 168 (41.2%) were H3 methylation dominant group. The latter showed the longer patients’ disease free survival (p=0.0359, logrank). In conclusion, our data suggest that the global histone modification patterns of H3 and H4 in NSCLC evaluated by immunohistochemistry is related to tumor recurrence and disease free survival.(This work is supported by KOSEF research grant R01-2004-000-10670-0).

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA