盆腔高级别浆液性癌中输卵管伞端上皮病变的病理学特征

Morphologic features of fallopian tubal epithelium in pelvic high-grade serous carcinoma

目的 探讨盆腔高级别浆液性癌（HGSC）中输卵管伞端上皮病变的病理学特征,及盆腔HGSC新分类的应用价值.方法 收集2015年6月至2016年12月58例盆腔HGSC（卵巢54例、输卵管3例、腹膜1例）和25例盆腔其他病变（包括卵巢低级别浆液性癌5例、卵巢子宫内膜样癌9例、卵巢透明细胞癌11例）患者的输卵管,按照广泛逐层切取检查法取材和切片,采用免疫组织化学EnVision法检测输卵管上皮p53和Ki-67表达情况,观察输卵管伞端上皮p53印记、浆液性输卵管上皮内病变（STIL）、浆液性输卵管上皮内癌（STIC）和浸润性癌的发生情况,并按照新分类标准重新分类.结果 58例盆腔HGSC中,输卵管上皮p53印记、STIL、STIC和输卵管浸润性癌的发生率分别为27.6%（16/58）、43.1%（25/58）、36.2%（21/58）和67.2%（39/58）,其中8例存在p53印记、STIL、STIC和输卵管浸润性癌谱系改变;而对照组25例盆腔其他病变患者输卵管p53印记、STIL、STIC和输卵管浸润性癌的发生率分别为24.0%（6/25）、0、0和8%（2/25）.盆腔HGSC中STIL、STIC和输卵管浸润性癌的发生率明显高于对照组,差异均有统计学意义（P〈0.01）.其中80.0%（20/25）STIL和85.7%（18/21）STIC病变累及单侧输卵管.根据新分类标准,重新分类为17例卵巢HGSC、40例输卵管HGSC和1例腹膜HGSC.结论 输卵管伞端存在p53印记、STIL、STIC与输卵管浸润性癌等一系列谱系性改变,表明伞端可能是盆腔HGSC的起始发生部位.STIL是比STIC更早期、可识别的输卵管上皮内病变,二者是HGSC特征性改变,可作为肿瘤早期发现和干预指标.按照新分类标准,更多HGSC被认为起源于输卵管,这有助于加深对肿瘤发生的理解,并对肿瘤的预防和早期干预具有潜在影响.

Objective To study the pathologic features of fallopian tubal epithelium in patients with pelvic high-grade serous carcinoma （HGSC）, to investigate its role in pelvic serous carcinogenesis and to reclassify the primary site of HGSC based on recently proposed criteria.Methods The fallopian tubes in 58 cases of pelvic HGSC （54 cases of ovarian primary, 3 cases of tubal primary, 1 case of peritoneum） and 25 cases of pelvic non-HGSC （5 cases of ovarian low-grade serous cancer, 9 cases of endometrioid cancer, and 11 cases of clear cell ovary carcinoma） were collected from June 2015 to December 2016, and serially examined under light microscope （SEE-FIM protocol）.Immunostaining for p53 and Ki-67 was performed to evaluate the presence of p53 signature, serous tubal intraepithelial lesion （STIL）, serous tubal intraepithelial carcinoma （STIC） and invasive carcinoma in these fallopian tubes.Meanwhile, primary site of HGSC based on the recently proposed diagnostic criteria were also reclassified.Results Among the study group, the frequencies of p53 signature, STIL, STIC and invasive HGSC were 27.6% （16/58）, 43.1% （25/58）, 36.2% （21/58） and 67.2% （39/58）, respectively, while in control group, the proportions were 24.0% （6/25）, 0, 0 and 8.0% （2/25）, respectively.The continuum of epithelial changes in the process of serous neoplasia including p53 signature, STIL, STIC and invasive carcinoma was identified in 8 cases of pelvic HGSC.The proportions of STIL, STIC and invasive carcinomas in HGSC group were higher than that in non-HGSC group （P〈0.01）.About 80.0% （20/25） of STIL and 85.7% （18/21） of STIC were present unilaterally.Diagnostically, the study group contained the 17 cases of ovarian HGSC, 40 cases of tubal HGSC, and 1 case of peritoneal HGSC after reclassification of the cancer primary.ConclusionsContinuous changes of tubal epithelium including p53 signature, STIL, STIC and invasive carcinomas are identified in patients with HGSC, supporting the current understanding that the fallopian tube is likely the cellular source of the majority HGSC.STIL and STIC may be specific to pelvic HGSC and may act as a target for future research on the early detection and prevention of this disease.The newly proposed diagnostic criteria for pelvic HGSC will lead us to more accurate classification of cancer primary sites.Correct classification of HGSC may have potential impacts for cancer prevention and improve our understanding of ovarian serous carcinogenesis.