PAX8 in Smooth Muscle Tumors of Mullerian Versus Non-Mullerian Origin
Anthony N Karnezis, Andrew E Horvai, Joseph T Rabban. University of California, San Francisco, CA
Background: Uterine smooth muscle tumors (SMT) and SMT of the retroperitoneum, mesentery, viscera or deep somatic soft tissue cannot be distinguished by routine light microscopy. Distinction of uterine smooth muscle tumors from non-uterine SMT is essential because of different criteria to classify malignant potential. Estrogen receptor (ER) immunohistochemistry (IHC) is of limited value due to low sensitivity and specificity for uterine SMT. PAX8, a transcription factor that regulates development of the Mullerian system, is expressed in normal Mullerian epithelium and in many Mullerian carcinomas. However, its expression in normal human myometrium and uterine SMT is unknown; the rare non-uterine SMT that have been studied do not express PAX8. Therefore, we evaluated the role of PAX8 in distinguishing uterine from non-uterine SMT and the concordance between PAX8 and ER in these tumors.
Design: We analyzed the expression of PAX8 and ER in uterine leiomyosarcoma (LMS, n=55, 14 primary and 41 metastatic), non-uterine LMS (n=23, retroperitoneal, mesenteric, pulmonary, inferior vena cava, gastric and soft tissue; 18 in women, 5 in men), uterine leiomyomas (n=12), parasitic leiomyomas of uterine origin (n=12) and visceral/gastrointestinal leiomyomas (n=3) by IHC on tissue microarrays. Stains were interpreted independently by the three authors who were blinded to the diagnoses. Tumors were scored for nuclear expression (negative/positive) and intensity of expression (0-3).
Results: PAX8 was expressed in 28 of 55 (51%) of uterine LMS, 12 of 23 (52%) of non-uterine LMS (including 3/5 occuring in men). Howewver, PAX8 was not expressed in any leiomyoma (0/27), regardless of origin. ER was expressed in 31 of 55 uterine LMS (56%) and 4 of 23 non-uterine LMS (17%, none in men). There was no correlation between PAX8 and ER expression in either uterine or non-uterine LMS, and the combination of PAX8 and ER expression was not significantly different between uterine and non-uterine LMS.
Conclusions: PAX8, either alone or in combination with ER, does not help discriminate between uterine and non-uterine origin of benign SMT or LMS. PAX8 expression in both uterine and non-uterine LMS, but not benign SMT, raises the possibility that this transcription factor may play a role in the pathogenesis of malignant tumors, irrespective of Mullerian origin.
Category: Gynecologic & Obstetrics
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 195, Wednesday Afternoon