Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm.
Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm.
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DOI：
10.1016/j.humpath.2011.03.003
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发表时间：
2011-07
期刊：
影响因子：
3.3
通讯作者：
Shih, Ie-Ming
中科院分区：
文献类型：
--
作者：
Kurman, Robert J.;Shih, Ie-Ming
最近的形态学，免疫组织化学和分子遗传学研究导致了一个新的模式的发病机制和起源的上皮性卵巢癌（EOC）的基础上的二元模型，将EOC分为两大类指定类型I和类型II。I型肿瘤包括低度浆液性、低度类浆液性、透明细胞和粘液性癌以及Brenner肿瘤。它们通常是惰性的，存在于I期（肿瘤局限于卵巢），并以特定的突变为特征，包括KRAS，BRAF，ERBB 2，CTNNB 1，PTEN PIK 3CA，ARID 1A和PPPR 1A，靶向特定的细胞信号传导途径。I型肿瘤很少携带TP 53，并且在遗传上相对稳定。II型肿瘤由高级别浆液性、高级别类胶质瘤、恶性混合性中胚层肿瘤（癌性肉瘤）和未分化癌组成。它们是侵袭性的，存在于晚期，并且具有非常高的TP 53突变频率，但很少具有在I型肿瘤中检测到的突变。此外，II型肿瘤的分子改变通过基因突变或启动子甲基化干扰BRCA的表达。这些肿瘤的一个特点是它们在遗传上高度不稳定。最近的研究强烈表明，输卵管上皮（良性或恶性），种植在卵巢是低级别和高级别浆液性癌的来源，而不是卵巢表面上皮细胞如以前所认为的。同样，人们普遍认为子宫内膜异位症是卵巢样癌和透明细胞癌的前体，并且认为子宫内膜异位症是由月经逆行引起的，因此这些肿瘤也可以被认为是继发于卵巢。粘液性和移行细胞（Brenner）肿瘤的起源仍然没有得到很好的确定，虽然最近的数据表明可能起源于位于输卵管-腹膜交界处卵巢旁位置的移行上皮巢。因此，现在看来，I型和II型卵巢肿瘤独立发展沿着不同的分子途径，这两种类型的发展卵巢外，并涉及它其次。如果这一概念得到证实，就会得出这样的结论：唯一真正的原发性卵巢肿瘤是类似于睾丸肿瘤的性腺基质和生殖细胞肿瘤。这种卵巢癌发生的新模式具有重要的临床意义。通过将卵巢癌发生的早期事件转移到输卵管和子宫内膜而不是卵巢，预防方法，例如保留卵巢的输卵管切除术，可能在减少卵巢癌负担同时保留激素功能和生育能力方面发挥重要作用。
Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a dualistic model of carcinogenesis that divides EOC into two broad categories designated type I and type II. Type I tumors are comprised of low-grade serous, low-grade endometrioid, clear cell and mucinous carcinomas and Brenner tumors. They are generally indolent, present in stage I (tumor confined to the ovary) and are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type I tumors rarely harbor TP53 and are relatively stable genetically. Type II tumors are comprised of high-grade serous, high-grade endometrioid, malignant mixed mesodermal tumors (carcinosarcomas) and undifferentiated carcinomas. They are aggressive, present in advanced stage, and have a very high frequency of TP53 mutations but rarely harbor the mutations detected in type I tumors. In addition, type II tumors have molecular alterations that perturb expression of BRCA either by mutation of the gene or by promotor methylation. A hallmark of these tumors is that they are genetically highly unstable. Recent studies strongly suggest that fallopian tube epithelium (benign or malignant) that implants on the ovary is the source of low-grade and high-grade serous carcinoma rather than the ovarian surface epithelium as previously believed. Similarly, it is widely accepted that endometriosis is the precursor of endometrioid and clear cell carcinomas and as endometriosis is thought to develop from retrograde menstruation these tumors can also be regarded as involving the ovary secondarily. The origin of mucinous and transitional cell (Brenner) tumors is still not well established, although recent data suggest a possible origin from transitional epithelial nests located in paraovarian locations at the tubo-peritoneal junction. Thus, it now appears that type I and type II ovarian tumors develop independently along different molecular pathways, and that both types develop outside the ovary and involve it secondarily. If this concept is confirmed it leads to the conclusion that the only true primary ovarian neoplasms are gonadal stromal and germ cell tumors analogous to testicular tumors. This new paradigm of ovarian carcinogenesis has important clinical implications. By shifting the early events of ovarian carcinogenesis to the fallopian tube and endometrium instead of the ovary, prevention approaches, for example, salpingectomy with ovarian conservation, may play an important role in reducing the burden of ovarian cancer while preserving hormonal function and fertility.
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影响因子：
7.3
作者：
Ahmed, Ashour Ahmed;Etemadmoghadam, Dariush;Temple, Jillian;Lynch, Andy G.;Riad, Mohamed;Sharma, Raghwa;Stewart, Colin;Fereday, Sian;Caldas, Carlos;DeFazio, Anna;Bowtell, David;Brenton, James D.
通讯作者：
Brenton, James D.
影响因子：
4.7
作者：
Gemignani, ML;Schlaerth, AC;Boyd, J
通讯作者：
Boyd, J
DOI：
10.1097/01.pgp.0000101082.35393.84
发表时间：
2004-01-01
影响因子：
2.4
作者：
Carcangiu, ML;Radice, P;Pasini, B
通讯作者：
Pasini, B
影响因子：
5.6
作者：
Burks, RT;Sherman, ME;Kurman, RJ
通讯作者：
Kurman, RJ
影响因子：
6
作者：
Gamallo, C;Palacios, J;Armas, A
通讯作者：
Armas, A