An Immunohistochemically Defined Correlate (PAX2-null SCOUTs) of Concurrent High-Grade Serous Carcinoma That Resides in the Fallopian Tube.
Charles M Quick, Geng Ning, Anna R Laury, Sara O Vargas, Frank D McKeon, Eleanor Y Chen, Wa Xian, Christopher P Crum. Brigham and Women's Hospital, Boston, MA
Background: Secretory cell outgrowths (SCOUTS) are discrete expansions of tubal epithelium that share loss of PAX2 expression with high-grade serous carcinoma; and, in one recent study (Chen 2010), were observed more frequently in cases of serous carcinoma. This study computed the frequency of PAX2-null SCOUTs (PAX2NS) in tubes of a range of conditions, including prepubertal, reproductive age (tubal ligation and benign disorders), endometriomas and low-grade endometrioid carcinomas of the ovary as well as high-grade serous carcinomas (HGSCA).
Design: A series of 167 cases (65 benign \ non-lesional controls, 14 ovarian HGSCAs, 41 low grade ovarian endometrioid adenocarcinomas, and 47 ovarian endometriomas) were culled from divisional files. Immunohistochemical staining for PAX2 was performed on all sections of fallopian tube, and null areas with traditional SCOUT morphology were counted. The PAX2-null SCOUTS (PAX2NS) were scored as events per cross section of fallopian tube (n=1200 cross sections), and data compiled as an average per histologic cross section.
Results: Patient age ranged from 26 to 84 (average 49 years). The frequency of sections with PAX2NS ranged from 0 – 0.11 in pre-adolescents and benign controls to 0.042-0.066 in endometrioid lesions. In contrast, the percentage of PAX2NS sections in HGSCA was 0.314, a highly significant difference relative to the other groups by chi square analysis (p < .001). Moreover, the disparity in average frequency of PAX2NS per section was greatest when comparing benign samples (0.0-0.11), endometrioid lesions (0.045-0.085) and HGSCA (0.562) (p < 0.001). The patient groups with a higher frequency of PAX2NS were older on average, and SCOUTs tended to cluster at greater frequency around 50 and 65 years of age. However, at any age, the frequency was always higher in the group with HGSCA.
Conclusions: This study reveals, for the first time, an immunohistochemically detectible entity (PAX2-null SCOUT) in benign tubal mucosa that is strongly associated with high-grade serous carcinoma relative to benign conditions and endometrioid neoplasia. This supports further the concept that the fallopian tube is not only a site of origin for HGSCA but harbors alterations in gene function in the benign epithelium that could signal either the presence, or greater risk, of pelvic serous cancer.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 11:00 AM
Platform Session: Section D, Tuesday Morning