Medeiros Fabiola, Muto Michael G, Lee Yonghee, Elvin Julia A, Callahan Michael J, Feltmate Colleen, Garber Judy E, Cramer Daniel W, Crum Christopher P
Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Am J Surg Pathol. 2006 Feb;30(2):230-6. doi: 10.1097/01.pas.0000180854.28831.77.
A proportion of adenocarcinomas in prophylactic adnexectomies (bilateral salpingo-oophorectomies [BSOs]) from women with BRCA mutations (BRCA positive) occur in the fallopian tube. We analyzed a consecutive series of BSOs from BRCA-positive women following an index case of fimbrial serous carcinoma. To determine if the fimbria is a preferred site of origin, we followed a protocol for Sectioning and Extensively Examining the FIMbria (SEE-FIM). Immunostaining for p53 and Ki-67 was also performed. Thirteen BRCA-positive women (cases) and 13 women undergoing BSOs for other disorders (controls) were studied. Tubal carcinoma was detected in 4 cases at the initial histologic evaluation and in no controls. A fifth carcinoma was discovered following further sectioning of the fimbriae. Three were BRCA2 positive and two BRCA1 positive. Three were in the fimbria, one in both the fimbria and proximal tube, and one involved the ampulla. Four were serous carcinomas, four were confined to the tube, and three were noninvasive (intraepithelial). No ovarian carcinomas were identified. All tumors were Ki-67 positive (>75% of cell nuclei), and excluding one endometrioid carcinoma, p53 positive (>75% cell nuclei); p53 positivity in the absence of elevated Ki-67 did not correlate with morphologic neoplasia. The fimbria was the most common location for early serous carcinoma in this series of BRCA-positive women. Protocols that extensively examine the fimbria (SEE-FIM) will maximize the detection of early tubal epithelial carcinoma in patients at risk for ovarian cancer. Investigative strategies targeting the fimbriated end of the fallopian tube should further define its role in the pathogenesis of familial and sporadic ovarian serous carcinomas.
在接受预防性附件切除术(双侧输卵管卵巢切除术[BSO])的携带BRCA突变(BRCA阳性)女性中,一部分腺癌发生于输卵管。我们分析了一系列BRCA阳性女性在发生首例输卵管浆液性癌后的连续BSO病例。为确定输卵管伞端是否为优先起源部位,我们遵循了输卵管伞端切片及全面检查方案(SEE-FIM)。同时还进行了p53和Ki-67免疫染色。研究了13例BRCA阳性女性(病例组)和13例因其他疾病接受BSO的女性(对照组)。初始组织学评估时在4例病例中检测到输卵管癌,对照组未检测到。在对输卵管伞端进一步切片后又发现1例癌。3例为BRCA2阳性,2例为BRCA1阳性。3例位于输卵管伞端,1例同时累及输卵管伞端和近端,1例累及壶腹部。4例为浆液性癌,4例局限于输卵管,3例为非浸润性(上皮内)。未发现卵巢癌。所有肿瘤Ki-67均呈阳性(>75%的细胞核),除1例子宫内膜样癌外,p53均呈阳性(>75%的细胞核);p53阳性而Ki-67未升高与形态学肿瘤形成无关。在这组BRCA阳性女性中,输卵管伞端是早期浆液性癌最常见的部位。广泛检查输卵管伞端的方案(SEE-FIM)将最大限度地检测出卵巢癌高危患者的早期输卵管上皮癌。针对输卵管伞端的研究策略应进一步明确其在家族性和散发性卵巢浆液性癌发病机制中的作用。