TP53 Mutations in Uterine Atypical Leiomyomas
Elisabetta Kuhn, Anna Yemelyanova, Tian-Li Wang, Robert J Kurman, Ie-Ming Shih. Johns Hopkins Medical Institutions, Baltimore, MD
Background: Most uterine smooth muscle tumors can be broadly subdivided into two groups: leiomyoma (including variant subtypes) and leiomyosarcoma based on cytologic atypia, mitotic activity and coagulative tumor cell necrosis. A small number defies classification into unequivocally benign and unequivocally malignant categories and are classified as “atypical leiomyoma” and “STUMP”. These two latter tumor types generally behave in a benign fashion but some are malignant. Morphologic and immunohistochemical studies designed to identify the malignant subset have thus far been unsuccessful. Although p53 overexpression as determined by immunohistochemical staining has been reported in these tumors, it is uncertain whether atypical leiomyomas harbor TP53 mutations. We therefore performed a mutational analysis of atypical leiomyomas to determine their TP53 mutation status.
Design: A total of 13 atypical leiomyomas were analyzed for TP53 mutations. In 7 cases marked cytologic atypia was diffusely present and in 6 it was focal. In tumors with focal atypia, manual microdissection was employed to separately dissect the atypical and conventional leiomyoma areas. DNA samples were sequenced and TP53 mutations were analyzed from exons 4 to 9.
Results: TP53 mutations were detected in 8 (62%) of 13 atypical leiomyomas. Of the 8 tumors with mutations, 5 had morphologically distinct components composed of atypical and conventional leiomyoma areas. In three of these 5 cases, a TP53 mutation was detected in the atypical component but not in the conventional leiomyoma area. In addition, there were three atypical leiomyomas that were associated with conventional leiomyomas and of those, one atypical leiomyoma harbored a TP53 mutation and the concurrent conventional leiomyoma did not. The other two contained wild-type TP53 in both the atypical and conventional leiomyomas.
Conclusions: The findings in this study indicate that, as currently defined, the group of tumors designated “atypical leiomyoma” is heterogeneous at least based on the presence of TP53 mutations. It is tempting to speculate that those harboring TP53 mutations represent the subset of atypical leiomyomas that are malignant. As follow-up information was not available in this study we were unable to confirm this hypothesis. Accordingly, future correlated molecular genetic and clinicopathologic studies in which follow-up information is available are necessary to clarify this important finding.
Category: Gynecologic & Obstetrics
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 182, Monday Morning