NHERF1 (Na+/H+ exchanger regulatory factor 1) is expressed in the
luminal membrane of many epithelia, and associated with
proteins involved in
tumor progression. Alterations of NHERF1 expression in different sites of metastatic
colorectal cancer (mCRC) suggest a dynamic role of this
protein in colon
carcinogenesis. We focused on the observation of the altered expression of NHERF1 from non-neoplastic tissues to metastatic sites by immunohistochemistry. Moreover, we studied, by immunofluorescence, the colocalization between NHERF1 and the
epidermal growth factor receptor (EGFR), whose overexpression is implicated in CRC progression. NHERF1 showed a different localization and expression in the examined sites. The distant non-neoplastic tissues showed NHERF1 mostly expressed at the apical membrane, while in surrounding non-neoplastic tissue decreased the apical membrane and increased cytoplasmic immunoreactivity. In
adenomas a shift from apical membrane to cytoplasmic localization and nuclear expression were observed. Cytoplasmic staining in the
tumor, and metastatic sites was stronger than surrounding non-neoplastic tissue. Furthermore, nuclear NHERF1 expression was noted in 80% of all samples and surprisingly, it appeared already in
adenoma lesions, suggesting that NHERF1 represents an early marker of pre-morphological triggering of colorectal
carcinogenesis. Then, in few
tumors a positive direct correlation between membrane NHERF1 and EGFR expression was evidenced by their colocalization. Nuclear NHERF1 expression, present in the early stages of
carcinogenesis and related with poor prognosis, may contribute to the onset of malignant phenotype. Specifically, we hypothesize the direct involvement of nuclear NHERF1 in both
carcinogenesis and progression and its role as a potential
colorectal cancer marker.