Ning Gang, Bijron Jonathan G, Yuan Ju, Hirsch Michelle S, McKeon Frank D, Nucci Marisa R, Crum Christopher P, Xian Wa
Department of Cell Biology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Int J Gynecol Pathol. 2013 Jul;32(4):345-52. doi: 10.1097/PGP.0b013e31826feee2.
Serous tubal intraepithelial carcinoma (STIC) is a noninvasive phase of pelvic serous cancer at risk for metastasizing. Because of its biologic significance, its accurate distinction from nonmalignant mimics is important. Loss of cell orientation is an important feature of STIC. We sought to determine whether the immunohistochemical localization of cytoskeletal-organizing proteins phospho-ezrin-radaxin-moesin (p-ERM) would be useful in making this distinction. The benign oviductal entities (normal and p53 signatures), premalignant atypias (tubal intraepithelial lesions in transition), serous intraepithelial carcinomas (STICs), and carcinomas were analyzed for 5 staining patterns and compared. Linear or uniform luminal p-ERM staining was strongly associated with benign mucosa in contrast to STICs, in which it was lost and often replaced by nonlinear or nonuniform patterns highlighting individually cell groups or single cells. Premalignant atypias were similar to benign mucosa by p-ERM staining and retained the linear luminal pattern. This study shows, for the first time, that patterns of staining for an immunohistochemical correlate of cell polarity (p-ERM) differ between STICs, their benign counterparts and premalignant atypias that do not fulfill the criteria for STICs. If confirmed, these findings warrant further analysis of indices of cell polarity as objective markers for the diagnosis and mapping of the evolution of pelvic serous precursors.
浆液性输卵管上皮内癌(STIC)是盆腔浆液性癌的非侵袭性阶段,有转移风险。因其生物学意义,准确区分它与非恶性的相似病变很重要。细胞极性丧失是STIC的一个重要特征。我们试图确定细胞骨架组织蛋白磷酸化埃兹蛋白-根蛋白-莫埃辛(p-ERM)的免疫组化定位在进行这种区分时是否有用。对良性输卵管实体(正常和p53特征)、癌前不典型病变(过渡中的输卵管上皮内病变)、浆液性上皮内癌(STIC)和癌进行了5种染色模式的分析并比较。与STIC相反,线性或均匀的管腔内p-ERM染色与良性黏膜密切相关,在STIC中这种染色会丧失,常被突出单个细胞群或单个细胞的非线性或不均匀模式所取代。癌前不典型病变在p-ERM染色方面与良性黏膜相似,保留线性管腔模式。本研究首次表明,细胞极性免疫组化相关物(p-ERM)的染色模式在STIC、其良性对应物以及不符合STIC标准的癌前不典型病变之间存在差异。如果得到证实,这些发现值得进一步分析细胞极性指标,将其作为盆腔浆液性癌前病变诊断和演变图谱的客观标志物。