FKBP51 is a promising biomarker for early cancer detection

Very recently, we have identified FKBP51, an immunophilin phisiologically expressed in lymphocytes, as a protein associated with malignant melanoma. Its expression correlates with tumor aggressiveness and is maximal in metastatic lesions. We have also demonstrated that FKBP51 is a factor of resistance to genotoxic agents because it promotes NF-κB activation. Aim of the present study was to investigate FKBP51 expression in solid tumors. Overall 71 samples, stored in our Patology section, of the following tumors: breast, colon, lung, pancreas, ovary and prostate (10 for each tumor, with exception of colon for which 21 samples were analyzed), and a comparable number of normal tissue samples, were analysed for FKBP51 expression, by immunohistochemistry. An intense signal was observed in all prostatic, ovarian and lung adenocarcinomas analyzed and in 8 out of 10 pancreatic cancers. Immunohistochemistry was low positive/negative in breast cancer. Normal tissues of the same histotype showed very low or undetectable levels of FKBP51, except for colon. FKBP51 was expressed in normal colonic mucosa, particularly in proliferative basal zone of normal glands. Nevertheless, an increased expression was found in 15 out of 21 tumor analyzed. Interestingly, we found that in colon carcinoma FKBP51 localization changed with grading. The protein was mostly cytosolic in G1, whereas it was always nuclear in G3. A nuclear localization was also observed in lung cancer. We also measured FKBP51 mRNA levels in deparaffinized tissues both normal and tumoral, by Realtime PCR. All normal tissues, except for prostate, displayed mRNA levels lower than those of PBL. FKBP51 levels in prostate and PBL were similar. Increases in mRNA levels, from 3 to 30 folds, were found in prostate, ovary, colon and lung cancers, compared to normal tissue of the same histotype. A correlation of gene expression with grading has been found in pancreatic adenocarcinoma. In undifferentiated carcinoma, an increase of more than 200fold of FKBP51 mRNA level was found, compared to normal tissue, whereas a moderate 2-4 fold increase was found in G2 tumors and no increase in G1. Very low levels were found in breast cancer, although higher than in normal tissue. In conclusion, our results show that FKBP51 expression increases in different solid tumors in comparison with the normal tissue counterpart. This study supports the conclusion that deregulated FKBP51 plays a role in malignant transformation.