Immunohistochemistry (IHC) for detecting key signal molecules involved in programmed cell death (PCD) in archival human pathology specimens is fairly well established. Detection of cleaved
caspase-3 in lymphocytes in
rheumatoid arthritis (RA) and gastric surface foveolar glandular epithelia but not in synoviocytes in RA, gastric fundic glandular epithelia, or nasal NK/
T-cell lymphoma (NKTCL) cells suggests anti-apoptotic mechanisms in cell differentiation and in
oncogenesis such as the induction of
survivin. Enzymatically pretreated and ultra-super sensitive detection of
beclin-1 in synoviocytes in RA and gastric fundic glandular epithelia suggests enhanced autophagy. The deposition of
beclin-1 in fibrinoid
necrosis in RA and expression of
beclin-1 in detached gastric fundic glandular cells suggest that enhanced autophagy undergoes autophagic cell death (ACD). NKTCL exhibited enhanced autophagy through LC3 labeling and showed densely LC3 labeled cell-debris in regions of peculiar
necrosis without deposition of
beclin-1, indicating massive ACD in NKTCL and the alternative pathway enhancing autophagy following autophagic vesicle nucleation. Autophagy progression was monitored by labeling aggregated mitochondria and
cathepsin D. The cell-debris in massive ACD in NKTCL were positive for
8-hydroxydeoxyguanosine, suggesting
DNA oxidation occurred in ACD. Immunohistochemical autophagy and PCD analysis in archival human pathology specimens may offer new insights into autophagy in humans.