Uterine Leiomyomata with Bizarre Nuclei: Expression of p53 and p16ink4 Is Common; However, Mutations of TP53 Are Rare and May Be Associated with Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome
Liping Liu, Chad LaGrange, Xiaoqiong Liu, Yuanyuan Zhang, Hui Zhang, Dali Huang, Timothy C Greiner, Julia Bridge, Subodh M Lele. University of Nebraska Medical Center, Omaha, NE
Background: Leiomyoma with bizarre nuclei (BL) can be confused with atypical leiomyoma or smooth muscle tumor of uncertain malignant potential, making predictions of biologic behavior imprecise. Thresholds for mitotic count and/or Ki67 expression to distinguish these neoplasms vary in different studies. Recent studies have proposed p53 and p16 INK4 expression analysis may be useful in predicting behavior. Although expression of p53 and p16 has been reported in BL, to our knowledge, no study identifying TP53 mutations in BL with follow-up data has been published. In this study, we examined BL [including those arising in the setting of hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC)] for expression of p53, p16 INK4 and Ki67, and TP53 mutation(s).
Design: Consecutive cases diagnosed as BL (n=11) with <2 mitoses/10 hpf (from 11 patients) with follow-up data were utilized. Representative sections were immunostained for p53, p16 INK4 and Ki67. Expression of p53 and p16 INK4 was assessed using the H-score [summation of the product of staining intensity (0-3) and proportion of cells staining (0-1) with a score range of 0-3]. Ki-67 expression was determined as a percentage of nuclear staining. TP53 mutation analysis on exons 5-8 was performed on microdissected lesional tissue using Sanger sequencing.
Results: The 11 cases (age range: 27-54 years) had a follow-up period of 3-96 months. No recurrences were noted. One case had HLRCC. The Ki67 index ranged from 0-1%. p53 expression was strong and diffuse (H-score: 2.25-3) in 4 cases and moderate-weak (H-score:1.2 and 1.6) in 2 cases. p16 INK4 was diffusely and strongly expressed in 4 cases (H-score: 2.4-2.85) and moderate-weak in 2 cases (H-score: 1.2 and 1.4). 4 cases had expression of both markers; however, only one case had strong and diffuse expression of both. The case with HLRCC had strong expression of p53 and moderate-weak expression of p16 INK4. TP53 mutation analysis revealed only one case (with HLRCC) with a missense mutation (Arg273Cys) and a base pair deletion [amino acid 288, del(A)] leading to a frameshift mutation on exon 8.
Conclusions: Expression of p53 and/or p16 INK4 is frequent (60%) in BL. However, mutations of TP53 are rare (9%). The presence of a TP53 mutation does not seem to impact the behavior. Identification of TP53 mutation(s) in BL may suggest an association with HLRCC and follow up with renal imaging studies.
Category: Gynecologic & Obstetrics
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 180, Monday Morning