Morphology and immunohistochemical staining for H3K36me3. H3K36me3 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the tri-methylation at the 36th lysine residue that, among other functions, maintain the gene expression stability. The trimethylation is catalyzed by SETD2, that acts as a tumor suppressor gene (TSG). Among the nine examined cases by IHC, all the seven SETD2-mutated cases were negative for H3K36me3. Only cases 6 and 8 had no SETD2 mutation. Case 5 (SETD2 mutation and normal copy number of 3p21) showed negativity for H3K36me3. Case 6 (no mutations in SETD2 and loss of 3p21) showed positivity for H3K36me3. ((a,c): hematoxylin and eosin, (b,d): H3K36me3).