Fallopian Tube as Main Source for Ovarian and Pelvic (Non-Endometrial)Serous Carcinomas

Abstract

In 2012, it is estimated that 22,280 new cases of ovarian carcinoma will be diagnosed in the United States, with 15500 associated deaths [1]. The high case fatality rate of ovarian cancers, most of which are high-grade serous adenocarcinomas, can be attributed to the advanced stage at which most patients with this disease present, and their attendant poor prognoses at this stage [2]. Attempts at screening and early detection of ovarian cancer, using a combination of transvaginal ultrasounds, measurements of serum CA-125 and other biomarkers, have largely been unsuccessful due to their lack of sufficient specificity and sensitivity in the general population [3][4][5]. Prophylactic oophorectomies, which surveys shown are performed in a substantial portion of postmenopausal women [6][7][8][9], remain a subject of debate as a way a reducing the mortality of ovarian cancers. In any event, the failure of most current preventive methods is evidenced by the fact that the overall mortality for ovarian carcinoma has largely remained unchanged for several decades [10]. A logical approach to a seemingly intractable problem is to re-assess and question some fundamental assumptions, in this case the cell and organ of origin for "ovarian" or pelvic non-endometrial serous carcinomas. In this regard, the last decade has seen the emergence of a robust body of evidence that implicates the fallopian tube as the origin for most pelvic serous carcinomas that have traditionally been assumed to be of ovarian origin [11].Several theories of ovarian carcinogenesis have been proposed over the years. Most assume the ovarian surface epithelium undergo malignant transformation. In incessant ovulation theory, a perpetual cycle of damage and repair of the ovarian surface epithelium increases the risk of malignant transformation [12]. The hormonal theory postulates that estrogen and gonadotropins cause stimulation and proliferation, and potentially malignant transformation of the ovarian surface epithelium [13]. Ovarian inclusions cysts are thought to develop from the ovarian surface epithelium, possibly after ovulation [14,15]. Based on morphologic observations [16], the fact that inclusions are more commonly identified in the ovary contralateral to cancerharboring ovaries [17,18], and the extremely rare occurrence of early serous carcinomas within the inclusions [19,20], it was assumed that after the ovarian surface epithelium invaginates into the underlying stroma to form inclusions, it undergoes mullerian metaplasia under the influence of the local stromal microenvironment [20,21], then potentially undergoes malignant transformation resulting in carcinomas corresponding to the different cell types (serous, endometrioid, clear cell, mucinous and transitional cell). The notion that the ovarian surface epithelium is the source for ovarian serous carcinomas has endured for decades, its relatively weak evidentiary basis notwithstanding, due to the absence of a competing theory that can incorporate the available evidence into a convincing and log...

Primary sources of pelvic serous cancer in patients with endometrial intraepithelial carcinoma

“…44 TP53 alteration has a key role in endometrial serous carcinoma carcinogenesis. 6,38,45 Studies have shown high prevalence of TP53 mutations in endometrial serous carcinoma and its noninvasive form serous endometrial intraepithelial carcinoma (up to 90% and 80%, respectively). 24,26,36 TP53-mutation analysis well defines the cellular lineage between primary organ sites and potential metastasis including serous endometrial intraepithelial carcinoma and associated extrauterine disease.…”

“…Pelvic serous carcinoma is mainly derived from adnexa and endometrial serous carcinoma. 6 Endometrial serous carcinoma without myometrial invasion, or serous endometrial intraepithelial carcinoma, is defined morphologically as the replacement of endometrial surface epithelium and/or glands by malignant serous cells. [7][8][9][10][11] To some, serous endometrial intraepithelial carcinoma is synonymous with stage IA endometrial serous carcinoma or minimal uterine serous carcinoma when tumor size is less than 1 cm.…”

Effect of prophylactic salpingectomy on ovarian function in premenopausal women in tertiary referral center

“…4 At present investigative efforts that are aimed at reducing the incidence of, and mortality from pelvic (non-endometrial) serous carcinomas should be focused on the fallopian tube, as the current state of evidence indicates that this is their site of origin in most cases, particularly because all previous attempts for screening programs could not be successfully implemented. 2,5 Therefore, careful and well-designed clinical trials for pelvic serous carcinoma prevention by removal of fallopian tubes or their fimbriated ends are justified and should be conducted. 5 It is currently recommended to perform prophylactic salpingectomy during hysterectomy for benign lesions [e.g.…”

“…2,5 Therefore, careful and well-designed clinical trials for pelvic serous carcinoma prevention by removal of fallopian tubes or their fimbriated ends are justified and should be conducted. 5 It is currently recommended to perform prophylactic salpingectomy during hysterectomy for benign lesions [e.g. fibromyoma or endometrial hyperplasia without atypia] which is still a common procedure.…”

Fallopian tube pathology – New findings: A review

“…In spite of traditional guidelines laid down to categorize a tumor as adnexal serous carcinoma, most are being classified as ovarian. [4] The evidences cited now in favor of primary fallopian origin are as follows: 1. The dysplastic, intraepithelial lesions predominantly identified in fallopian tube and not in the ovaries in riskreducing salpingo-oophorectomy specimens of women at increased risk for ovarian carcinomas.…”