Autophagy proteins in prostate cancer: relation with anaerobic metabolism and Gleason score.

OBJECTIVES

Up-regulation of autophagy provides an important survival mechanism to normal and malignant cells residing in a hypoxic and unfavorable nutritional environment. Yet, its role in the biology of prostate cancer remains poorly understood.

METHODS

In this study we investigated the expression of four major autophagy proteins, namely the microtubule-associated protein 1 light chain 3A (LC3A), LC3B, Beclin 1, and p62, together with an enzyme of anaerobic metabolism, the lactate dehydrogenase 5 (LDH5), in relation to Gleason score and extraprostatic invasion. A series of 96 prostate adenocarcinomas was examined using immunohistochemical techniques and appropriate antibodies.

RESULTS

The LC3A protein was expressed in the form of "stone-like" structures, and diffuse cytoplasmic staining, the LC3B reactivity was solely cytoplasmic, whereas that of p62 and LDH5 was both cytoplasmic and nuclear. A median count of 0.90 "stone-like" structures per 200 × optical field (range 0-3.6) was highly associated with a high Gleason score. Similarly, a strong cytoplasmic LC3A, LC3B, and p62 expression, when extensive (present in>50% tumor cells per section), was significantly associated with LDH5 and a high Gleason score. In addition, extensive cytoplasmic p62 expression was related with LC3A and B reactivity and also with extraprostatic invasion. Extensive Beclin-1 expression was significantly linked with extraprostatic invasion and also with p62 and LDH5 expression.

CONCLUSIONS

Immunohistochemical detection of autophagy proteins may potentially prove to be useful as prognostic markers and a tool for the stratification of patients in therapeutic trials targeting autophagy in prostate cancer.