University of Nebraska Medical Center, Omaha, NE 68198.
University of Nebraska Medical Center, Omaha, NE 68198.
Hum Pathol. 2018 Mar;73:122-127. doi: 10.1016/j.humpath.2017.12.020. Epub 2018 Jan 4.
Morphologically, distinguishing between leiomyoma (LM) and leiomyosarcoma (LMS) is not always straightforward, especially with benign variants such as bizarre leiomyoma (BLM). To identify potential markers of malignancy in uterine smooth muscle tumors, proteomic studies were performed followed by assessment of protein expression by immunohistochemistry. Archival formalin-fixed, paraffin-embedded tissues from tumors (n = 23) diagnosed as LM, BLM, and LMS (using published criteria) were selected for the study. Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry was applied to pooled samples of formalin-fixed, paraffin-embedded LM and LMS tumor tissue to assay the relative protein quantities and look for expression patterns differentiating the 2 tumor types. A total of 592 proteins were quantified, and 10 proteins were differentially expressed between LM and LMS. Select proteins were chosen for evaluation by immunohistochemistry (IHC) based on antibody availability and biologic relevance in the literature. IHC was performed on a tissue microarray, and intensity was evaluated using imaging software. Major vault protein (MVP) and catechol O-methyltransferase had 3.05 and 13.94 times higher expression in LMS relative to LM by sequential window acquisition of all theoretical fragment ion spectra mass spectrometry, respectively. By IHC, MVP (clone 1014; Santa Cruz Biotechnology, Dallas, TX) was found to be 50% sensitive and 100% specific when comparing LMS to LM. Catechol O-methyltransferase (clone FL-271; Santa Cruz Biotechnology) had a sensitivity of 38% and a specificity of 88%. Six of 7 BLM had expression of MVP similar to LM. Immunohistochemical staining for MVP is a useful adjunct in distinguishing LMS from LM and BLM in difficult cases.
形态学上，区分平滑肌瘤（LM）和平滑肌肉瘤（LMS）并不总是那么容易，尤其是对于良性变体，如奇异型平滑肌瘤（BLM）。为了确定子宫平滑肌肿瘤恶性的潜在标志物，进行了蛋白质组学研究，然后通过免疫组织化学评估蛋白质表达。选择存档的福尔马林固定、石蜡包埋的肿瘤组织（n=23），这些肿瘤根据发表的标准诊断为 LM、BLM 和 LMS，用于本研究。对福尔马林固定、石蜡包埋的 LM 和 LMS 肿瘤组织的混合样本应用连续窗口采集所有理论片段离子谱质谱，以测定相对蛋白质数量，并寻找区分 2 种肿瘤类型的表达模式。共定量了 592 种蛋白质，其中 10 种蛋白质在 LM 和 LMS 之间表达差异。根据抗体可用性和文献中生物学相关性，选择一些蛋白质进行免疫组织化学（IHC）评估。在组织微阵列上进行 IHC，并使用成像软件评估强度。连续窗口采集所有理论片段离子谱质谱显示，大 vault 蛋白（MVP）和儿茶酚-O-甲基转移酶在 LMS 中的表达分别比 LM 高 3.05 倍和 13.94 倍。通过 IHC，当比较 LMS 与 LM 时，MVP（克隆 1014；Santa Cruz Biotechnology，达拉斯，TX）的敏感性为 50%，特异性为 100%。儿茶酚-O-甲基转移酶（克隆 FL-271；Santa Cruz Biotechnology）的敏感性为 38%，特异性为 88%。7 例 BLM 中有 6 例的 MVP 表达与 LM 相似。免疫组织化学染色 MVP 有助于在困难病例中区分 LMS 与 LM 和 BLM。
