Expression Analysis of Autophagy Related Markers LC3B, p62 and HMGB1 Indicate an Autophagy-Independent Negative Prognostic Impact of High p62 Expression in Pulmonary Squamous Cell Carcinomas

Autophagy is involved in maintaining cellular homeostasis under stress conditions. It also plays an important role in various diseases including cancer. Pulmonary squamous cell carcinomas (pSQCC) at present lack targetable molecular alterations, and demand alternative therapeutic options. We assessed the expression levels of autophagy related proteins LC3B, p62, and HMGB1 in 271 primary resected pSQCC by immunohistochemistry, in correlation with clinical and pathological parameters, as a rationale for a potential autophagy directed therapy. LC3B, p62, and HMGB1 staining showed various patterns. LC3B(high)p62(low) levels, suggested to indicate intact activated autophagy, were associated with prolonged disease specific survival (DSS) and LC3B(high)p62(high) levels, indicating activated but late stage impaired autophagy, with shorter DSS (p = 0.024). p62(high) expression regardless of LC3B, however, showed an even stronger association with shorter DSS (p = 0.015) and was also an independent negative prognostic factor in multivariate analysis (HR = 2.99; 95% CI 1.38-6.52; p = 0.006). HMGB1 expression correlated neither with the expression of LC3B and p62, nor with patients' outcome. Different states of autophagy characterized by distinct p62 and LC3B expression patterns may be linked to patient's prognosis in pSQCC. Our results, however, point also to an autophagy independent role of p62 with an even more pronounced prognostic impact compared to autophagy related p62.