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

Abstract

With the exception of germ-line mutations in ovarian cancer susceptibility genes, genetic predictors for women destined for ovarian serous cancer cannot be identified in advance of malignancy. We recently showed that benign secretory cell outgrowths (SCOUTs) in the oviduct are increased in frequency with concurrent serous cancer and typically lack PAX2 expression (PAX2-null). The present study examined the relationship of PAX2-null SCOUTs to high-grade serous cancers by comparing oviducts from women with benign gynecologic conditions and high-grade serous cancers. PAX2-null SCOUTs were identified by immunostaining and computed as a function of location, frequency (F) per number of cross-sections examined, and age. Six hundred thirty-nine cross-sections from 35 serous cancers (364) and 35 controls (275) were examined. PAX2-null SCOUTs consisted of discrete linear stretches of altered epithelium ranging from cuboidal/columnar, to pseudostratified, the latter including ciliated differentiation. They were evenly distributed among proximal and fimbrial tubal sections. One hundred fourteen (F=0.31) and 45 (F=0.16) PAX2-null SCOUTs were identified in cases and controls, respectively. Mean individual case-specific frequencies for cases and controls were 0.39 and 0.14, respectively. SCOUT frequency increased significantly with age in both groups (P=0.01). However, when adjusted for age and the number of sections examined, the differences in frequency between cases and controls remained significant at P=0.006. This study supports a relationship between discrete PAX2 gene dysregulation in the oviduct and both increasing age and, more significantly, the presence of co-existing serous cancer. We propose a unique co-variable in benign oviductal epithelium—the PAX2-null SCOUT—that reflects underlying dysregulation in genes linked to serous neoplasia.