Int J Gynecol Cancer. 2018 Feb;28(2):363-370. doi: 10.1097/IGC.0000000000001160.
Class V Beta tubulin isotype (βV-tubulin) was recently found to have tissue-specific expression patterns in epithelial tissues with secretory function and aberrant expression in tumors. The aims of this pilot study were (a) to examine expression of βV-tubulin in the fallopian tube epithelium (FTE) of patients who underwent salpingectomy, (b) to characterize FTE atypia in high-risk patients with BRCA mutations, and (c) to determine expression of βV-tubulin in serous ovarian neoplasms.
Immunohistochemistry, with a highly specific antibody developed in our laboratory against human βV-tubulin, was used to evaluate expression in paraffin-embedded sections of the fallopian tube (n = 82) and tumors (n = 13), from prospectively selected cases, categorized by reason for salpingectomy.
βV-tubulin, when present, was expressed in secretory cells and essentially never in ciliated cells of the FTE. Histologically "normal" FTE had very rare, scattered βV-tubulin-positive cells; percentage positivity increased in cases of serous ovarian neoplasms. The highest expression was observed in FTE from patients with BRCA mutant breast cancer. Four distinct types of FTE atypia were delineated in patients with known BRCA mutations. In a few additional test cases of ovarian neoplasms, βV-tubulin was highly expressed, with the extent and intensity of staining elevated in high-grade serous carcinomas compared with serous borderline tumors.
In summary, βV-tubulin was localized to secretory cells of the distal FTE and its expression varied according to the clinical diagnosis. The frequency of these cells and thus expression of βV-tubulin were dramatically enriched in tissue obtained from BRCA mutant cases, which also exhibited pronounced histologic atypia indicative of early predysplastic aberrations. Furthermore, elevated expression of βV-tubulin correlated with poor differentiation status in serous ovarian neoplasms.
βV 微管蛋白同种型(βV-tubulin)最近在具有分泌功能的上皮组织中发现具有组织特异性表达模式,并且在肿瘤中表达异常。本研究的目的是:(a)检测接受输卵管切除术的患者输卵管上皮(FTE)中βV-tubulin的表达;(b)描述 BRCA 突变高危患者的 FTE 非典型性;(c)确定浆液性卵巢肿瘤中βV-tubulin的表达。
使用我们实验室针对人βV-tubulin 开发的高度特异性抗体,通过免疫组织化学方法对来自前瞻性选择病例的输卵管(n=82)和肿瘤(n=13)的石蜡包埋切片进行评估,这些病例根据输卵管切除术的原因进行分类。
βV-tubulin 存在时,表达于 FTE 的分泌细胞中,而在纤毛细胞中基本不存在。组织学“正常”的 FTE 中βV-tubulin 阳性细胞很少且分散;浆液性卵巢肿瘤病例中阳性细胞百分比增加。BRCA 突变乳腺癌患者的 FTE 表达最高。在已知 BRCA 突变的患者中,确定了 4 种不同类型的 FTE 非典型性。在少数其他卵巢肿瘤的测试病例中,βV-tubulin 高度表达,与浆液性交界性肿瘤相比,高级别浆液性癌中染色的程度和强度更高。
总之,βV-tubulin 定位于 FTE 的远端分泌细胞,其表达根据临床诊断而变化。这些细胞的频率及其βV-tubulin 的表达在 BRCA 突变病例中明显丰富,这些病例还表现出明显的组织学非典型性,表明早期前发育异常。此外,βV-tubulin 的高表达与浆液性卵巢肿瘤的分化状态不良相关。