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[Cancer Research 61, 2537-2541, March 15, 2001]
© 2001 American Association for Cancer Research

Endocrinology

Decreased Expression of Estrogen Receptor ß Protein in Proliferative Preinvasive Mammary Tumors1

Pascal Roger, Majida Esslimani Sahla, Sari Mäkelä, Jan Åke Gustafsson, Pierre Baldet and Henri Rochefort2

Laboratoire de Biologie Cellulaire et Hormonale, Hôpital Arnaud-de-Villeneuve, 34059 Montpellier Cédex, France [H. R.]; Laboratoire d’Anatomie et Cytologie Pathologiques, Hôpital Lapeyronie, 34059 Montpellier Cédex, France [P. R., P. B.]; Endocrinologie Moléculaire et Cellulaire des Cancers (U 540) INSERM, 34090 Montpellier, France [P. R., M. E. S., H. R.]; and Department of Biosciences and Medical Nutrition, Karolinska Institute, Novum, Huddinge University Hospital, S-141 86 Huddinge, Sweden [S. M., J. A. G.]

To understand the significance of estrogen receptor ß (ERß) in mammary carcinogenesis, we evaluated the expression of ERß in preinvasive mammary tumors. The percentage of ERß-positive epithelial or tumoral cells was assayed by quantitative immunohistochemistry using an image analyzer in 130 lesions of varying histological risk from 118 patients [71 with benign breast disease (BBD) and 59 with carcinoma in situ (CIS)] and compared with 118 adjacent histologically normal glands. Five groups of lesions with an increasing risk of invasive cancer, from BBD without hyperplasia to high-grade CIS, were studied. Results were compared with ER{alpha} and Ki67 immunostaining. The percentage of ERß-positive cells was high (median, 85%) in "normal" mammary glands and in nonproliferative BBD and decreased significantly (P < 0.0001) in proliferative BBD without atypia and in CIS, contrasting with an inverse progression for the ER{alpha} level. In normal mammary glands, the ERß level did not vary according to the nature of the lesion at the periphery and was significantly higher (P < 0.007) than in adjacent preinvasive lesions, except in nonproliferative BBD. The ERß level decreased in proliferative BBD, anticipating the ER{alpha} increase, which was significant in BBD with atypia. In high-grade ductal carcinoma in situ, both ER levels were low. The ratio between ERß and ER{alpha} was high in normal glands, and decreased significantly in proliferative lesions. ERß staining was inversely correlated with Ki67 (r = -0.333; P < 0.001), more particularly in high-grade ductal carcinoma in situ (r = -0.57; P < 0.02). The marked and early decreased level of ERß protein associated with other criteria of cell proliferation suggests a protective effect of ERß against the mitogenic activity of estrogens in mammary premalignant lesions. Knowledge of the ERß and ER{alpha} content in each preinvasive lesion should help to rationalize antiestrogen preventive therapy adapted to each individual patient.




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