The use of immunohistochemical labeling to identify patterns of proliferation and protein expression in smooth muscle tumors of the uterus.

Leiomyomas (fibroids) are the most common benign tumors of the uterus and are present in greater than half the female population over 50 years old in the United States. Leiomyosarcomas are the malignant variation of leiomyomas and, while far less common, have a high mortality rate. Differential protein expression between both benign and malignant tumors and normal tissue samples forms the basis of many treatment strategies. This study evaluated protein expression of several markers using immunohistochemistry (IHC) methods on 74 leiomyomas, 14 uterine leiomyosarcomas, and 26 normal uterine myometrial samples which had been formalin-fixed and paraffin-embedded. Markers included the Ki-67 proliferation marker, estrogen receptor (ER), progesterone receptor (PR), aldehyde dehydrogenase (ALDH), B-cell lymphoma 2 (BCL-2), and cytokeratin 8/18 (CK 8/18). The Ki-67 positivity was significantly higher in leiomyosarcomas when compared with benign uterine tissues and was also higher in leiomyomas than in normal uterine smooth muscle. ER and PR were highly expressed in benign tissues but exhibited reduced expression in malignant lesions. Both CK 8/18 and ALDH were expressed in a significantly higher proportion of normal myometrial tissues as compared with leiomyomas and leiomyosarcomas. Conversely, BCL-2 expression in normal tissues was lower than in both leiomyomas and leiomyosarcomas with leiomyosarcomas producing the highest expression. The Ki-67 value can reliably differentiate between benign and malignant smooth muscle uterine tissues. Because CK 8/18 and ALDH were more frequently or strongly expressed in normal myometrium vs. leiomyoma or leiomyosarcoma, pathological changes to the cells may be the cause for a reduction in protein production. Future investigations may determine that upregulation of either of these two markers in leiomyomas or leiomyosarcomas could lead to slower tumor growth.