Fallopian Tube Correlates of Ovarian Serous Borderline Tumors

Abstract

Ovarian serous borderline tumors (SBTs) are presumed to originate in the ovarian cortex or peritoneal surface. The pathogenetic role of the fallopian tube (FT) is unclear but recently, secretory cell outgrowths (SCOUTs) lacking PAX2 expression have been described in benign FTs. This study addressed 1) the differentiation characteristics of SBTs, 2) the frequency of SCOUTs lacking PAX2 expression in the fallopian tubes of patients with SBTs, and compared 3) SCOUT morphology and 4) PAX2 expression with SBTs. SBTs and FT epithelium shared both ciliated (p73) and secretory (HMFG2) differentiation. PAX2-null SCOUT frequency in FT cross sections from patients with SBTs was 0.27 (110/398) versus 0.09 in benign hysterectomies and nearly zero in pediatric and post partum sterilization specimens. (p=<0.001). When adjusted for age, the differences narrowed but remained significant (p = 0.010). SCOUTs were heterogenous, some displaying ciliated differentiation and papillary architecture. Two cases of discrete multi-focal papillary SCOUTs in the fallopian tube were associated with SBTs. All SBTs had heterogeneous PAX2 staining with areas of PAX2 loss. This study shows for the first time that PAX2-null SCOUTs are more common in the oviducts of women with SBTs and that loss of PAX2 expression occurs in most SBTs. These discoveries link both morphologic and functional gene (PAX2) alterations in the oviduct to SBTs, similar to that reported in high grade serous carcinoma. Further study is warranted to clarify the relationship of the oviduct to serous neoplasia.

PAX2-null secretory cell outgrowths in the oviduct and their relationship to pelvic serous cancer

“…15 It is important to emphasize that PAX2-null SCOUTs with normal p53 expression appear to be distributed equally in fimbrial and proximal oviductal sections, shown by Chen et al 14 and confirmed in this report. Thus, the absence of PAX2-null SCOUTs in pediatric and post-partum sterilization tubal sections is significant despite the limited sampling of the tubes in these populations.…”

“…14 However, SCOUTs were evenly distributed in the tube being no more prevalent in the fimbria than proximal segments. 14,15 From this, we concluded that SCOUTs reflected pathway disturbances that, while more prevalent in women with high-grade serous cancers, were not direct precursors to serous cancer. Nevertheless, loss of PAX2 staining was also highly prevalent in p53 signatures, secretory cell expansions with p53 mutations that are candidate precursors.…”

“…14,16 We have recently found that borderline serous tumors, which are not associated with loss of p53 function, also show an increase in PAX2-null secretory outgrowths in their oviducts and also display focal loss of PAX2 immunostaining. 15 Such associations emphasize the need for more study to resolve the significance of SCOUTs in pelvic epithelial tumorigenesis. What is clear is that although they are discrete in appearance, PAX2-null SCOUTs, like p53 signatures, do not harbor a marked increase in proliferative index (Ning G, unpublished data).…”

“…In two additional control groups consisting of pediatric autopsy cases and tubal sterilizations from another study, the frequency approached zero (Figure 3). 15 …”

“…The latter question was prompted by the exceedingly low frequency of PAX2-null SCOUTs in pediatric autopsy specimens and post-partum tubal sterilizations, two groups considerably younger on average than women undergoing surgery for benign disease and malignancies. 15 We addressed these questions in a regression model that adjusted for age, as well as the number of cross-sections on the frequency of PAX2-null SCOUTs by linear regression analysis. For cases and controls, each group was divided according to 10-year intervals (26-35, 36-45, 46-55, 56-65, etc) and the average frequencies for the intervals were compared ( Figure 5).…”