Immunoexpression of p16 in uterine leiomyomas with infarct type necrosis

Abstract

BACKGROUND: The cell cycle marker p16 has been shown to be overexpressed in uterine leiomyosarcomas and theoretically useful for distinguishing between benign and malignant smooth muscle tumors. Its use is limited in routine practice because it has been noted to show variable expression in benign histological variants, specifically, leiomyoma with bizarre nuclei, a tumor that is difficult to distinguish from leiomyosarcoma. The expression of p16 in other benign variants, particularly those with problematic histological features, has seldom been studied. DESIGN: p16 expression pattern in 35 benign uterine leiomyomas with infarct type necrosis were studied. Any staining in the nucleus and/or cytoplasm was considered positive. The extent of positive staining surrounding the infarct was classified as none, <33%, 33-66% and >66%. The extent of staining in areas away from the infarct was classified as none, scattered/isolated, <33%, 33-66% and >66%. Clinical and drug histories and follow-up were also obtained. RESULTS: Age of patients was 23-55 years (median, 43.6), and presentations were menorrhagia, pain, mass, or combinations thereof. 25 were treated with hysterectomy and the remainder with myomectomy. Preoperative drugs (oral contraceptives/GnRH-a/tranexamic acid) were prescribed in 18. One was pregnant. Tumor sizes ranged from 1.5-24 cm (mean, 7.8). All tumors had absent-to-mild atypia except for one case in which the atypia was mild-to-moderate. The mean mitotic count was 1.4/10HPFs (ranged 0-16). All had unequivocal infarct-type necrosis. The extent of p16 positivity in areas surrounding the infarct was 0 in 3 cases (8.6%); <33% in 25 cases (71.4%); 33-66% in 4 cases (11.4%) and >66% in 3 cases (8.6%). The extent of p16 positivity in areas away from the infarct was 0 in 4 cases (11.4%); scattered/isolated in 21 cases (60%); <33% in 8 cases (22.9%); 33-66% in 1 case (2.9%) and >66% in 1 case (2.9%). None of the patients, including those with tumors that showed >66% p16 positivity, developed recurrence after a mean follow-up of 41.4 months (range 1-126). CONCLUSIONS: p16 expression in benign uterine leiomyomas with infarct type necrosis is common, particularly concentrated in tumor cells surrounding an infarct. Its utility in leiomyomas with uncertain type of necrosis may be limited. [Equal contributions from authors 1&2].