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MASATSUGU UEDA, YOSHIKI YAMASHITA, MIKIO TAKEHARA, YOSHITO TERAI, KOJI KUMAGAI,

KEN UEKI, KOJI KANDA, HIROYUKI YAMAGUCHI, DAISUKE AKISE, YAO-CHING HUNG, AND

MINORU UEKI

Department of Obstetrics and Gynecology (Ma.U., Y.Y., M.T., Y.T., K.Ku., K.U., K.Ka., H.Y., D.A., Mi.U.), Osaka Medical

College, Osaka 569-8686, Japan; and Department of Obstetrics and Gynecology (Y.-C.H.), China Medical College, Taiwan,

Republic of China†R

Survivin is a novel inhibitor of apoptosis (normal cell death) and is expressed during fetal development and in cancer tissues, but its expression has not been reported in normal adult tissues or benign diseases. We investigated survivin gene and protein expression in a tumor-like benign disease, endometriosis, and correlated them with apoptosis and invasive phenotype of endometriotic tissues.

Gene expression levels of survivin, matrix metalloproteinase (MMP)-2, MMP-9, and membrane type 1 (MT1)-MMP in 63 pigmented or nonpigmented endometriotic tissues surgically obtained from 35 women with endometriosis were compared with those in normal eutopic endometrium obtained from 12 women without endometriosis.

Survivin, MMP-2, MMP-9, and MT1-MMP mRNA expression levels in clinically aggressive pigmented lesions were significantly higher than those in normal eutopic endometrium, and survivin gene expression in pigmented lesions was also higher than that in nonpigmented lesions (P < 0.05). There was a close correlation between survivin and MMP-2, MMP-9, or MT1-MMP gene expression levels in 63 endometriotic tissues examined (P<0.01). Apoptotic cells detected by thedUTP nick-end labeling were rare in 11 ovarian endometriotic tissues, which showed positive immunohistochemical expression for survivin and MMPs.

Our findings suggest that up-regulation of survivin and MMPs may cooperatively contribute to survival and invasion of endometriosis. (J Clin Endocrinol Metab 87: 3452–3459, 2002)