Nuclear expression of NHERF1/EBP50 in Clear Cell Renal Cell Carcinoma.

The Na/H exchange regulatory factor 1 or Ezrin-radixin-moesin-binding phosphoprotein 50 (NHERF1/EBP50) is an adaptor protein implicated in the stabilization of molecular complexes linking extracellular signals with the cytoskeleton machinery. NHERF1 expression at the cell cortex is associated with the maintenance of adherent junction integrity in polarized epithelia. The role of NHERF1 in cancer depends on its localization within the cell, acting, in most cases, as a tumor suppressor when localized at the cell membrane, and as an oncogene, when expressed in the cytoplasm or the nucleus of cancer cells. The distribution of NHERF1 in renal cell carcinoma (RCC) has not been yet investigated. In this study, NHERF1 expression was examined by immunohistochemistry in papillary and clear cell RCC. We observed membranous staining in papillary RCC, whereas NHERF1 expression was nuclear and membranous in clear cell RCC. In comparison, NHERF1 immunohistochemistry in clear cell carcinomas of the ovary showed mainly nuclear staining. Our finding of the specific NHERF1 nuclear expression in clear cell carcinomas may help to elucidate the molecular changes that regulate its nuclear accumulation and to better understand its role in this cell compartment.

Similar expression pattern of NHERF1 and EZRIN in papillary but not in solid areas of human serous ovarian carcinomas.

NHERF1 is an adaptor protein expressed in the apical membrane of polarized epithelia, which interacts with the EZRIN-Radixin-Moesin (ERM) family of proteins connecting signaling pathways to the cell cytoskeleton. NHERF1 and EZRIN cooperate in the maintenance of the apical microvilli in polarized epithelial cells. In several types of cancers, NHERF1 and EZRIN are displaced from the apical compartment to the cytoplasm and nuclei of cancer cells. At the present, the distribution of NHERF1 in ovarian tumors is not well known. In this study, NHERF1 expression was examined by immunohistochemistry in cyst adenofibromas, serous borderline tumors, and serous ovarian carcinomas. We observed a strong staining of NHERF1 and EZRIN at the membrane level of borderline tumors and areas of papillary structures in ovarian carcinomas. In tumors without papillary structures and compact structure, NHERF1 was exclusively expressed in the apical pole of the cells at the edges of the clefts of luminal spaces. In contrast, positive expression of EZRIN was found in the membrane of tumor cells within the solid tumor where NHERF1 was not expressed. In summary, this study shows, for the first time, the distribution of NHERF1 in ovarian cancer and reveals a different regulation of NHERF1 and EZRIN expression in ovarian tumors which represents the complexity of the molecular changes of this disease.

Patología de los carcinomas no invasores de la mama / Pathologic of the non invasive breast cancer

El carcinoma de la mama se origina, en su comienzo, como una proliferación atípica del epitelio de los lobulillos mamarios o de los conductos galactóforos, la que rellena, total o parcialmente, la luz de los mismos (carcinoma "in situ"); luego infiltra el estroma circundante convirtiéndose en un carcinoma invasor. Es decir que, a partir del epitelio normal de los conductos y de los lobulillos mamarios, en una progresión a través de estadios intermedios, se desarrolla el carcinoma de la mama, cuya fase más temprana y de mejor pronóstico, es la forma "in situ". De acuerdo con esto, los carcinomas mamarios pueden clasificarse como carcinomas no infiltrantes o no invasores (carcinoma "in situ"), carcinoma sin infiltración evidente del esoma) y carcinomas infiltrantes o invasores. En este capítulo haremos referencia a los distintos tipos de carcinomas "in situ" de la mama; creemos de importancia, antes de analizar los distintos tipos de carcinomas no invasores, hacer un breve resumen de la histogénesis del tejido glandular mamario