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Comparative Analysis of the ERα/ERβ Ratio and Neurotensin and its High-affinity Receptor in Myometrium, Uterine Leiomyoma, Atypical Leiomyoma, and Leiomyosarcoma

Rodríguez, Yurena G.St.; Báez, Delia M.D., Ph.D.; de Oca, Francisco Montes M.D., Ph.D.; García, Candelaria M.D., Ph.D.; Dorta, Idaira G.St.; Reyes, Ricardo Ph.D.; Valladares, Francisco Ph.D.; Almeida, Teresa A. Ph.D.; Bello, Aixa R. Ph.D.

International Journal of Gynecological Pathology: July 2011 - Volume 30 - Issue 4 - p 354–363
doi: 10.1097/PGP.0b013e31820918cb

Deregulated steroids are involved in different hormone-dependent tumors, including benign and malignant uterine neoplasms. Leiomyomas (LM) are estrogen and progesterone-dependent benign tumors, whereas “bizarre or atypical LMs” (AL) are considered a subgroup of LM and clinically benign, although their malignant potential is suspect. Uterine leiomyosarcomas (LMS) are malignant smooth muscle tumors, and ovarian steroids may control their growth. Estrogen effects are mediated by 2 receptors, estrogen receptors (ER) α and β, and the ratio of both receptors seems to be a critical parameter in the estrogen-mediated carcinogenic process. Estradiol induces the expression of neurotensin (NTS), and the coupling of this peptide with its high-affinity receptor, NTS1, has been involved in the regulation of tumoral cell growth. Given the importance of these markers in tumor development, we aim to determine the status of ERα and ERβ in the myometrium and LM, AL, and LMS, concomitantly with the expression of NTS/NTS receptor 1 in these tumors. For that purpose, we use immunohistochemistry for all markers analyzed and in-situ hybridization to detect NTS mRNA. These data suggest that LMS are estrogen-dependent tumors, which may use NTS as an autocrine growth factor. In addition, the phenotype of AL with regard to ERα and ERβ status and NTS expression is closer to LMS than LM; thus, a potential malignization of this tumor is feasible.

Departamento de Microbiología y Biología Celular, (Y.R., I.D., R.R., A.R.B.), Àrea de Biología Celular, Facultad de Biología

Instituto de Enfermedades Tropicales (T.A.A.), Laboratorio de Genética

Departamento de Anatomía, Anatomía Patológica e Histología (F.V.), Facultad de Medicina

Departamento de Obstetricia y Ginecología (D.B.), Facultad de Medicina, Universidad de La Laguna

Hospital Universitario de Canarias (HUC) (C.G.), La Laguna

Hospital La Colina (USP) (F.M.deO.), Santa Cruz

Fundación Canaria del Instituto Canario de Investigación del Cáncer (Y.R., D.B., C.G., I.D., R.R., F.V., T.A.A., A.R.B.), Tenerife, Spain

Supported in part by: FICIC (Fundación Canaria del Instituto Canario de Investigación del Cáncer), Gobierno de Canarias PI2007/001, and FUNDACIÓN 2000 grants to Yurena Rodríguez and Idaira Dorta.

Address correspondence and reprint requests to Aixa R. Bello, PhD, Área de Biología Celular, Universidad de La Laguna, Facultad de Biología, Avenida Astrofísico Francisco Sánchez s/n, 38206 La Laguna, Tenerife, Spain. e-mail:

©2011International Society of Gynecological Pathologists