Mutually Exclusive Expression of PAX8 and p63 in Transitional Cell Tumors of the Ovary
Melanie R Hawver, Jian-Jun Wei, Xiao-Wei Chen, Diane Hamele-Bena, Jason Wright, Guo-Xia Tong. Columbia University Medical Center, New York, NY; Northwestern University, Chicago, IL
Background: Transitional cell tumors of the ovary(OTCT) include benign, borderline and malignant Brenner tumors(BT) and transitional cell carcinoma of the ovary(OTCC). All are uncommon, collectively comprising less than 2% of ovarian tumors. They histologically resemble urothelial neoplasms of the urinary tract, potentially posing diagnostic pitfalls. PAX8 is a developmental transcription factor and a diagnostic and histogenetic marker for Müllerian epithelial tumors. Its expression has not been fully examined in OTCT. In this study, we investigate the expression of PAX8 in OTCT utilizing immunohistochemistry(IHC) and provide additional information regarding the histogenesis and differential diagnosis of these intriguing tumors.
Design: 25 benign BT, 1 malignant BT, and 23 OTCC were retrieved, and a tissue microarray(TMA) was assembled with 3 cores from each case. Walthard rests(WR) from 5 salpingectomy specimens and TMA containing 41 invasive TCCs of the urinary bladder(UTCC) from radical cystectomy specimens were also examined. IHC with PAX8, p63, and CD44 was performed. Only distinct nuclear staining was considered to be positive for PAX8 and p63. The staining intensity was graded as negative, weak(1+), moderate(2+) and strong(3+).
Results: All of the WR and benign BT were strongly positive for p63, while all of the OTCC were negative. All WR and benign BT were negative for PAX8, while all of the OTCC and the 1 malignant BT were strongly and diffusely positive for PAX8. In addition, all of the WR and benign BT were 2+ for CD44, while OTCC showed variable staining for CD44(negative in 5, 1+ in 9, 2+ in 8, and 3+ in 1 case(s)). All of the UTCC were consistently negative for PAX8, but had variable staining for p63(negative in 13, 1+ in 25, 2+ in 2, 3+ in 1 case(s)). Staining of CD44 in UTCC was also variable(negative in 9, 1+ in 9, 2+ in 13, and 3+ in 10 cases).
Conclusions: We have demonstrated a mutually exclusive expression of PAX8 and p63 in OTCT. Detection of PAX8 in OTCC confirms that this tumor is of Müllerian origin and thus is a variant of common ovarian carcinomas. Absence of PAX8 in WR and benign BT suggests a non-Müllerian origin of these lesions. The dual positive staining of p63 and CD44 indicates that WR and benign BT immunohistochemically resemble the basal cells of the stratified epithelium. In summary, PAX8, in combination with p63, is a useful marker to distinguish benign BT from malignant BT and OTCC. Furthermore, PAX8 is more reliable than p63 and CD44 in distinguishing OTCC from metastatic UTCC in the ovary.
Category: Gynecologic & Obstetrics
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 156, Wednesday Morning