Expression and localization of the immunophilin FKBP51 in colorectal carcinomas and primary metastases, and alterations following oxaliplatin-based chemotherapy.

The immunophilin FK506-binding protein 5 (FKBP51) is a scaffold protein that serves a pivotal role in the regulation of multiple signaling pathways, integrating external and internal stimuli into distinct signal outputs. In a previous study, we identified several genes that are significantly up- or downregulated in the peripheral white cells (PWCs) of colorectal adenocarcinoma (CRC) patients undergoing oxaliplatin-based chemotherapy. In our screening, FKBP51 gene expression was downregulated following chemotherapy. In order to determine whether this alteration in gene expression observed in PWCs may be detected at the protein level in tumors and metastases following the administration of adjuvant chemotherapy, an immunohistochemical analysis of FKBP51 in CRC and primary metastasis tissues was performed. The present study confirmed the downregulation of FKBP51 gene expression elicited by chemotherapy with folinic acid (leucovorin), fluorouracil and oxaliplatin in metastasized liver tissue that had been resected after the oxaliplatin-based chemotherapy, compared with tissue section samples of CRC from patients (prior to antineoplastic treatment). Furthermore, the results indicated that, in CRC tissue sections, the expression of FKBP51 protein is associated with an immature phenotype of stromal fibroblasts and with the epithelial-to-mesenchymal transition (EMT) phenotype, suggesting a role for this protein in the EMT process in CRC. Finally, the observation that only certain cells of the stroma express FKBP51 protein suggests a potential role for this immunophilin as a stroma cell subtype marker.

CD34-positive fibroblasts in Reinke's edema.

OBJECTIVES/HYPOTHESIS: To elucidate whether and to what extent CD34+ fibroblasts (so-called CD34+ fibrocytes, CD34+ dendritic cells, and CD34+ stromal cells) occur in normal human vocal folds and in Reinke's edema. STUDY DESIGN: Histological study. METHODS: Conventional, immunohistochemical, and ultrastructural procedures were performed in histological blocks of 18 selected cases of Reinke's edema (with typical findings including acellular edematous spaces in the subepithelial connective tissue of vocal folds, and disarrangement of elastic, collagen, and reticular fibers). For control purposes, four normal vocal folds were analyzed. RESULTS: In normal vocal folds, most stromal cells were spindle-shaped CD34+ fibroblasts. In Reinke's edema, increased density and changes in the morphology and size of this subpopulation of fibroblasts were demonstrated in the connective tissue surrounding the edematous spaces, particularly in their borders, where together with some macrophages they formed boundaries, mimicking the walls of distended lymphatic vessels when conventional stains were used. These activated CD34+ fibroblasts acquired a dendritic morphology (with long, moniliform, often bifurcated, overlapping multipolar processes), and their cytoplasmic organelles were increased in number. In addition to CD34, they expressed vimentin, CD10 and CD99, but no α-smooth muscle actin (α-SMA), CD31, CD117, CD68, h-caldesmon, desmin, or S-100 protein. CONCLUSIONS: CD34+ fibroblasts are a major cell component in the stroma of vocal folds in Reinke's edema, and their activation, with increased density and morphologic changes around the edematous spaces, occurs without immunophenotypic transformation toward myofibroblasts (no expression of α-SMA). The mechanisms by which these cells act in Reinke's edema require further study.