Objective: The goal of this work was to determine whether exposure to estrogen following treatment of low-grade endometrial stromal sarcomas affects clinical outcome.
Methods: Twenty-two patients with low-grade endometrial stromal sarcomas were reviewed to determine whether they were exposed to exogenous or endogenous estrogen and/or progestins following their diagnosis and whether exposure to these hormones might have influenced their prognosis. Estrogen receptor (ER) alpha and beta and progestin receptor (PR) status were analyzed from paraffin-embedded tissue by immunohistochemistry and ER mRNA was measured in fresh tissue by reverse transcription polymerase chain reaction (RT-PCR).
Results: Ten of the twenty-two patients with low-grade endometrial stromal sarcomas developed recurrent disease. Four of five patients (80%) who received estrogen replacement therapy (ERT) recurred. Four of eight patients (50%) with retained ovaries recurred. Eight of the ten specimens available for analysis were positive for ERalpha, none were positive for ERbeta, and 9 of 10 were positive for PR. Four of thirteen patients who received progestins as adjuvant therapy recurred, compared with 6 of 9 patients who did not receive progestins (31% vs 67%). Eight recurrences were treated with progestin therapy and 7 (88%) of them had either stable disease (3/8, 38%) or complete response (4/8, 50%).
Conclusions: Our results suggest that ERT may be detrimental in patients with low-grade endometrial stromal sarcoma. Retention of normally functioning ovaries, on the other hand, may not significantly affect the recurrence rate following hysterectomy alone in Stage I patients. The lack of ERbeta expression in endometrial stromal sarcomas compared with normal endometrial stromal cells suggests that loss of ERbeta may be a marker for malignancy. Progestin therapy should be routinely considered for adjuvant therapy and for the treatment of recurrent endometrial stromal sarcomas.