[1142] Cell Cycle Regulatory Markers in Uterine Atypical Leiomyoma, Cellular Leiomyoma, STUMP and Leiomyosarcoma: Immunohistochemical Study of 74 Cases with Clinical Follow-Up
AM Mills, A Ly, BL Balzer, MR Hendrickson, RL Kempson, JK McKenney, TA Longacre. Stanford University, Stanford, CA
Background: Cell cycle regulatory protein expression may have diagnostic and prognostic value in distinguishing leiomyosarcoma from leiomyoma variants and in predicting recurrence for smooth muscle tumors of uncertain malignant potential (STUMP), but data - especially with clinical follow up - are limited.
Design: p16, p21, p27, p53, Ki67, and PHH3 protein expression was evaluated by immunohistochemistry (IHC) on full tissue sections of 44 atypical leiomyoma (AL), 8 cellular leiomyoma (CL), 6 STUMP, and 16 leiomyosarcoma (LMS). Nuclear staining was scored as absent (-), <33% (+), 33-66% (++), or >66% (+++). All results were correlated with clinical follow up, when available.
Results: Table 1 summarizes IHC staining for p16, p21, p27, and p53. Proliferation rate (Ki67) ranged from 0-25% in AL (mean, 2%), 0-10% in CL (mean, 3%), 0-10% in STUMP (mean,7.5%), and 6-50% in LMS (mean, 25%), while proliferation rate (PHH3) ranged from 0-3% in AL (mean, <1%), 0-2% in CL (mean, <1%), 0% in STUMP, and 0-10% in LMS (mean, 2%). Two of 35 AL had local recurrence following myomectomy at 24.9 and 25.7 mos (mean, 50.8). 7 of 8 LMS had local recurrence and/or distant metastasis (mean, 29.7 mos). There were no recurrences in 4 CL (mean, 22.6 mos) and 6 STUMP (mean, 16.2 mos) with follow up. The two AL with local recurrence showed only weak and focal (<33%) staining with all cell cycle markers aside from p21, which was diffusely positive in one case with recurrence.
| p16 | AL | CL | LMS | STUMP |
| - | 18% | 0% | 0% | 0% |
| + | 57% | 75% | 25% | 66% |
| ++ | 18% | 25% | 12% | 17% |
| +++ | 7% | 0% | 63% | 17% |
| p53 | ||||
| - | 67% | 12% | 19% | 0% |
| + | 14% | 50% | 44% | 100% |
| ++ | 12% | 38% | 12% | 0% |
| +++ | 7% | 0% | 25% | 0% |
| p21 | ||||
| - | 0% | 0% | 10% | 0% |
| + | 76% | 50% | 60% | 80% |
| ++ | 21% | 50% | 30% | 20% |
| +++ | 3% | 0% | 0% | 0% |
| p27 | ||||
| - | 10% | 0% | 20% | 0% |
| + | 52% | 50% | 20% | 60% |
| ++ | 31% | 50% | 20% | 20% |
| +++ | 7% | 0% | 40% | 20% |