Soong T Rinda, Kolin David L, Teschan Nathan J, Crum Christopher P
Department of Pathology, University of Washington Medical Center, Seattle, WA 98195, USA.
Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Cancers (Basel). 2018 Nov 28;10(12):468. doi: 10.3390/cancers10120468.
Beginning with the discovery of the -associated ovarian cancer susceptibility genes and subsequent detailed examination of risk-reducing salpingo-oophorectomy (RRSO) specimens, a new paradigm of ovarian carcinogenesis has unfolded with attention to the distal fallopian tube. The primary focus has been an early cancer or neoplasm in the fallopian tube which is seen in virtually all incidentally discovered high-grade serous cancers in asymptomatic women. This high-frequency of tubal involvement in early serous neoplasm (usually in the form of serous tubal intraepithelial carcinoma-STIC) has galvanized attention to this organ as a primary source of this disease. However, an enduring mystery has been the relatively low frequency of STIC in the fallopian tubes of women with advanced malignancy. This paradox, a high frequency of tubal involvement early on and a low frequency of involvement later in the disease process, has spurred interest in other potential sources, such as the ovarian surface epithelium or cortical inclusions and the secondary Mullerian system. However, because essentially all high-grade serous carcinomas are linked by mutations, and because fallopian tubes frequently contain early serous proliferations (ESPs) with these mutations, attention has turned to the possibility that the nonmalignant but mutated tubal epithelium could be responsible for an eventual malignancy. Recent data have shown evidence of a lineage continuity between ESPs and concurrent serous carcinomas prompting the concept of "precursor escape". This creates a second component of the paradigm by which cells from early precursors are shed from the tube and undergo subsequent malignant transformation, emerging suddenly as widespread intraperitoneal malignancy. This dualistic model thus provides a unique pathway by which the future outcome (wide spread high-grade serous carcinomas-HGSC) is ultimately explained by going back in time to an early serous proliferation. This paradigm also brings the peritoneal cavity into focus, raising new questions about the potential co-variables or exposures that might facilitate the occasional malignant transformation of an ESP in the peritoneal cavity or on the peritoneal surface.
从发现与卵巢癌相关的易感基因以及随后对降低风险的输卵管卵巢切除术（RRSO）标本进行详细检查开始，随着对远端输卵管的关注，卵巢癌发生的新范式逐渐显现。主要关注点是输卵管中的早期癌症或肿瘤，在无症状女性中几乎所有偶然发现的高级别浆液性癌中都能看到这种情况。早期浆液性肿瘤中输卵管受累的高频率（通常以浆液性输卵管上皮内癌-STIC的形式）已促使人们将注意力集中在这个器官上，将其视为这种疾病的主要来源。然而，一个长期存在的谜团是，在晚期恶性肿瘤女性的输卵管中，STIC的频率相对较低。这种矛盾现象，即疾病早期输卵管受累频率高而后期受累频率低，激发了人们对其他潜在来源的兴趣，如卵巢表面上皮或皮质包涵体以及副苗勒管系统。然而，由于基本上所有高级别浆液性癌都与特定基因突变相关，并且由于输卵管中经常含有具有这些突变的早期浆液性增殖（ESP），人们的注意力转向了这样一种可能性，即非恶性但发生突变的输卵管上皮可能是最终恶性肿瘤的病因。最近的数据显示了ESP与同期浆液性癌之间存在谱系连续性的证据，从而引出了“前体逃逸”的概念。这就形成了该范式的第二个组成部分，即早期前体细胞从输卵管脱落并经历随后的恶性转化，突然以广泛的腹腔内恶性肿瘤形式出现。这种二元模型因此提供了一条独特的途径，通过追溯到早期浆液性增殖来最终解释未来的结果（广泛传播的高级别浆液性癌-HGSC）。这个范式也将腹腔纳入了关注焦点，引发了关于可能促进ESP在腹腔内或腹膜表面偶尔发生恶性转化的潜在协变量或暴露因素的新问题。
