Immunoexpression of autophagy‑related proteins in a single‑center series of sporadic adult conventional clival chordomas

Autophagy is a biological process that facilitates the degradation and removal of damaged structures and macromolecules. In neoplasms, autophagy has been proposed to play a dual role, functioning either as a tumor promoter or a tumor suppressor. To date, no comprehensive analysis of autophagy, primarily through immunohistochemical investigation of autophagy-related proteins (ATGs), has been conducted in chordomas (CHs), which are rare bone tumors that arise from remnants of the notochord. The present study aimed to investigate the immunoexpression of several ATGs, including microtubule-associated protein 1 light chain 3 (LC3A/B), Sequestosome-1 (p62) and autophagy and Beclin 1 regulator 1 (AMBRA-1) in a series of sporadic adult conventional clival CHs collected from a single neuropathological center in southern Italy. Immunohistochemical analysis revealed that LC3A/B, p62 and AMBRA-1 were exclusively found in neoplastic cells, with no expression detected in the surrounding stromal cells. Both LC3A/B and p62 were expressed in the cytoplasm and nucleus of neoplastic cells, while AMBRA-1 was predominantly localized in the cytoplasm. In all cases of CHs, p62 was consistently and highly expressed, whereas a similarly high expression of LC3A/B was observed in five cases, four of which were characterized by neoplastic recurrence and partial resection. Low immunoreactivity was noted in seven out of 10 cases (70%), while three recurrent cases exhibited high levels of AMBRA-1 immunostaining. Statistical analysis using Fisher's exact test revealed significant P-values for LC3A/B (P=0.048), AMBRA-1 (P=0.033), Ki-67 (P=0.048) and surgical treatment (P=0.048). Consequently, a negative prognostic role for these two ATGs may be hypothesized in the development of CHs.