Autophagy and redox status in carcinoma of an unknown primary

Aim and background. The purpose of the study was to investigate the role and clinical implications of autophagy and reactive oxygen species-related proteins in carcinoma of an unknown primary (CUP).

Methods and study design. Tissue microarray was constructed for a total of 77 CUP cases. Immunohistochemical stains conducted were as follows: autophagy-related beclin-1, LC3A, LC3B, and p62; redox-related catalase, thioredoxin reductase, glutathione S-transferase p, thioredoxin-interacting protein, and manganese superoxide dismutase. Immunohistochemical results were then related to their clinicopathologic parameters.

Results. The degree of LC3A expression showed a difference according to histologic subtype. In undifferentiated carcinoma, LC3A had the highest expression and adenocarcinoma had the lowest expression (P = 0.021). According to clinical subtype, there was a significant difference between LC3A and glutathione S-transferase p in expression. LC3A had the highest expression in single-organ types and the lowest in intermediate and carcinomatosis types (P = 0.003). Glutathione S-transferase p showed the highest expression in nodal-type tumors and the lowest in carcinomatosis types (P = 0.010). In univariate analysis, shorter overall survival was related to tumor glutathione S-transferase p negativity (P = 0.030).

Conclusions. Different expression levels of the autophagy and reactive oxygen species-related proteins, LC3A and glutathione S-transferase p, were observed according to histologic and/or clinical subtype of carcinoma of an unknown primary.