Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Am J Surg Pathol. 2013 May;37(5):634-42. doi: 10.1097/PAS.0b013e318287779c.
Cell cycle regulatory protein expression by immunohistochemical assay may have diagnostic utility in the distinction of uterine leiomyosarcoma from leiomyoma variants. p16, p21, p27, and p53 protein expression was evaluated by immunohistochemistry on 44 atypical leiomyomas (mean follow-up, 50.8 mo), 16 leiomyosarcomas (mean follow-up, 29.7 mo), and 8 cellular leiomyomas (mean follow-up, 22.6 mo). Nuclear staining was semiquantitatively scored on 1 representative section per case as negative (0%), focal (>0% to 33%), patchy (>33% to 66%), or diffuse (>66%). In addition, staining intensity was noted as weak, moderate, or strong. Proliferative index was gauged by Ki-67 and PHH3 immunohistochemical staining. One of 35 atypical leiomyoma patients with follow-up data developed an extrauterine recurrence 25.7 months after hysterectomy, whereas a second had intrauterine recurrence 24.9 months after myomectomy. Seven of 8 patients with leiomyosarcoma with follow-up had recurrence within the follow-up period, whereas there were no recurrences in patients with cellular leiomyoma. The Ki-67 proliferation index ranged from 0% to 25% in atypical leiomyoma (mean, 2%) and 6% to 50% in leiomyosarcoma (mean, 25%) with 0% to 10% in cellular leiomyoma (mean, 3%), whereas the PHH3 proliferation index ranged from 0% to 3% in atypical leiomyoma (mean, <1%) and 0% to 10% in leiomyosarcoma (mean, 2%) with 0% to 2% in cellular leiomyoma (mean, <1%). The atypical leiomyoma with extrauterine recurrence was diffusely positive for p21, but showed only weak focal (<33%) staining for all other cell cycle markers. Uterine atypical leiomyomas, cellular leiomyomas, and leiomyosarcomas demonstrate a heterogenous pattern of cell cycle regulatory protein expression. Caution should be exercised in distinguishing leiomyosarcoma from atypical leiomyoma variants on the basis of cell cycle protein expression alone. In our study, cell cycle markers were not useful for predicting recurrence in atypical leiomyoma.
通过免疫组织化学检测细胞周期调控蛋白的表达可能有助于鉴别子宫平滑肌瘤和平滑肌瘤变体中的平滑肌肉瘤。对 44 例非典型平滑肌瘤（平均随访时间 50.8 个月）、16 例平滑肌肉瘤（平均随访时间 29.7 个月）和 8 例细胞性平滑肌瘤（平均随访时间 22.6 个月）进行了免疫组化检测 p16、p21、p27 和 p53 蛋白的表达。每个病例的 1 个代表性切片进行核染色半定量评分，结果为阴性（0%）、局灶性（>0%至 33%）、斑片状（>33%至 66%）或弥漫性（>66%）。此外，还记录了染色强度为弱、中或强。通过 Ki-67 和 PHH3 免疫组化染色评估增殖指数。有 35 例有随访数据的非典型平滑肌瘤患者中的 1 例在子宫切除术后 25.7 个月发生了子宫外复发，另 1 例在子宫肌瘤切除术后 24.9 个月发生了子宫内复发。8 例平滑肌肉瘤患者中有 7 例在随访期间复发，而细胞性平滑肌瘤患者无复发。非典型平滑肌瘤的 Ki-67 增殖指数为 0%至 25%（平均 2%），平滑肌肉瘤为 6%至 50%（平均 25%），细胞性平滑肌瘤为 0%至 10%（平均 3%），而 PHH3 增殖指数为 0%至 3%（平均 <1%），平滑肌肉瘤为 0%至 10%（平均 2%），细胞性平滑肌瘤为 0%至 2%（平均 <1%）。发生子宫外复发的非典型平滑肌瘤 p21 弥漫性阳性，但所有其他细胞周期标志物仅表现为弱阳性（<33%）局灶性染色。子宫非典型平滑肌瘤、细胞性平滑肌瘤和平滑肌肉瘤表现出细胞周期调节蛋白表达的异质性模式。仅根据细胞周期蛋白表达鉴别平滑肌肉瘤与非典型平滑肌瘤变体时应谨慎。在我们的研究中，细胞周期标志物对预测非典型平滑肌瘤的复发没有帮助。
