Jarboe Elke, Folkins Ann, Nucci Marisa R, Kindelberger David, Drapkin Ronny, Miron Alexander, Lee Yonghee, Crum Christopher P
Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Int J Gynecol Pathol. 2008 Jan;27(1):1-9. doi: 10.1097/pgp.0b013e31814b191f.
The fimbria is the most common site of early serous cancer (tubal intraepithelial carcinoma or STIC) in women with BRCA mutations (BRCA+). A candidate serous cancer precursor--the p53 signature--has been found in nonneoplastic secretory cells of the fimbria, suggesting serous carcinogenesis in the tube (SCAT). This study surveyed fallopian tubes from 3 populations to characterize the morphological and immunohistochemical correlates of SCAT. The SCAT sequence was defined by strong nuclear p53 staining and DNA damage (gamma-H2AX+) in secretory cells and subdivided morphologically by (1) degree of nuclear stratification, (2) proliferative index, and (3) degree of disorganized growth. Fallopian tubes from women without a current ovarian cancer, women with BRCA mutations, and women with a coexisting pelvic serous cancer were completely examined. p53 signatures exhibited cuboidal to pseudostratified, polarized p53+ epithelial segments with variable nuclear enlargement and a MiB1 index of 0% to 30%. Tubal intraepithelial carcinomas contained from single (uncommon) to multilayered, poorly polarized, uninterrupted neoplastic cell populations that completely displaced the normal mucosa; MiB1 index exceeded 45% and was usually more than 70%. An uncommon third category, p53-positive foci with features intermediate between p53 signatures and STICs, exhibited preserved epithelial polarity, pseudostratification, incomplete replacement of the adjacent normal ciliated cells, and a MiB1 index between 40% and 75%. Transitions from 1 category to another were documented. Combined with recent reports associating STICs with pelvic serous cancer, this continuum of epithelial change validates the SCAT sequence and the fimbrial secretory cell as the site of origin for many serous carcinomas.
在携带BRCA突变（BRCA+）的女性中，输卵管伞端是早期浆液性癌（输卵管上皮内癌或STIC）最常见的发生部位。在输卵管伞端的非肿瘤性分泌细胞中发现了一种潜在的浆液性癌前体——p53特征，提示输卵管浆液性癌发生（SCAT）。本研究对来自3个群体的输卵管进行了调查，以描述SCAT的形态学和免疫组化相关性。SCAT序列的定义为分泌细胞中强烈的核p53染色和DNA损伤（γ-H2AX+），并根据（1）核分层程度、（2）增殖指数和（3）生长紊乱程度进行形态学细分。对无当前卵巢癌的女性、携带BRCA突变的女性以及合并盆腔浆液性癌的女性的输卵管进行了全面检查。p53特征表现为立方形至假复层、极性p53+上皮段，核大小可变，MiB1指数为0%至30%。输卵管上皮内癌包含单个（不常见）至多层、极性差、不间断的肿瘤细胞群体，这些细胞群体完全取代了正常黏膜；MiB1指数超过45%，通常超过70%。第三种不常见的类型，即具有介于p53特征和STIC之间特征的p53阳性灶，表现为保留上皮极性、假复层、相邻正常纤毛细胞未完全被取代，MiB1指数在40%至75%之间。记录了从一种类型到另一种类型的转变。结合最近将STIC与盆腔浆液性癌相关联的报道，这种上皮变化的连续性证实了SCAT序列以及输卵管分泌细胞是许多浆液性癌的起源部位。
