Immunohistochemical Profiling of 312 Gynecologic and Soft Tissue Smooth Muscle Tumors
CH Lee, V Sung, K Montgomery, M van de Rijn, CB Gilks. Vancouver General Hospital, Vancouver, BC, Canada; Stanford University Medical Center, Stanford, CA
Background: Leiomyosarcomas (LMS) are malignant mesenchymal tumors that display smooth muscle differentiation. The gynecologic tract and the soft tissue compartments are the two most common sites of occurrence. There are some indications that LMS of gynecologic and non-gynecologic origins may be different. More importantly, particularly for the gynecologic LMS, distinction between malignant and benign smooth muscle tumors on morphologic grounds alone can be difficult at times.
Design: Using tissue microarrays that included 263 cases of LMS (106 gynecologic) and 49 cases of uterine leiomyoma (ULM), we examined the ability of selected markers to differentiate between malignant and benign gynecologic smooth muscle tumors (p16 and MIB-1) and between LMS of gynecologic and non-gynecologic origins (ER and WT1).
Results: Eighty-five percent of the gynecologic LMS and 2% of ULM displayed diffuse (50% of tumor cells) cytoplasmic and nuclear p16 staining. The majority of ULM showed focal (5-20%) p16 immunoreactivity (p<0.01). 81% of the gynecologic LMS and 0% of the ULM exhibited 10% MIB-1 proliferation index (p<0.01). A combination of the two markers (diffuse p16 and/or high proliferation index) yielded a detection sensitivity of 92% and a specificity of 99% for gynecologic LMS as compared to ULM. Non-gynecologic LMS showed similar p16 staining and MIB-1 proliferation index as gynecologic LMS. In differentiating between LMS of gynecologic and non-gynecologic origins, ER nuclear positivity is seen in 4% and 50% of the non-gynecologic and gynecologic LMS respectively (p<0.01), while WT1 nuclear/cytoplasmic positivity is seen in 51% and 55% of the non-gynecologic and gynecologic LMS, respectively. 100% and 90% of ULM were positive for ER and WT1, respectively.
Conclusions: The findings of diffuse p16 immunoreactivity and/or high MIB-1 proliferation index appear to be relatively sensitive and highly specific indicators of malignancy in gynecologic smooth muscle tumors. ER but not WT1 immuno-positivity can be used to support the gynecologic origin of a LMS.
Tuesday, March 10, 2009 11:45 AM
Platform Session: Section D, Tuesday Morning