PAX8 and PAX2 Immunostaining Facilitates the Diagnosis of Primary Epithelial Neoplasms of the Male Genital Tract

Abstract

PAX8 and PAX2 are cell-lineage-specific transcription factors that are essential for the development of Wolffian and Müllerian ducts and have recently emerged as specific diagnostic markers for tumors of renal or Müllerian origin. Little is known about their expression in the Wolffian duct-derived human male genital tract. We report our findings of PAX8 and PAX2 expression in the epithelium of the normal male genital tract and in epithelial tumors derived therefrom using immunohistochemistry (IHC). We found that PAX8 and PAX2 were expressed in the epithelium of the male genital tract from the rete testis to the ejaculatory duct. Rare glands in the prostatic central zone, a tissue of purported Wolffian duct origin, were focally positive for PAX2, but no PAX8 was detected in this area, a finding that may warrant further study. We found diffuse expression of PAX8 and PAX2 in 1 case each of serous cystadenoma of the epididymis, carcinoma of the rete testis, Wolffian adnexal tumor of the seminal vesicle, and endometrioid carcinoma of the seminal vesicle. Neither PAX8 nor PAX2 was detected in the seminiferous tubules and interstitium of the normal testis, nor in Leydig cell tumors (n=6), Sertoli cell tumors (n=2), or 48 of 49 germ cell tumors. One pediatric yolk sac tumor showed focal and weak staining for PAX8. Tumors of mesothelial origin, that is, adenomatoid tumors (n=3) and peritoneal malignant mesotheliomas (n=37) in men, were negative for PAX2 and PAX8. Neither PAX2 nor PAX8 was present in other areas of the prostate. Expression of PAX8 and PAX2 in these primary epithelial neoplasms of the male genital tract is due to their histogenetic relationship with Wolffian or Müllerian ducts. PAX8 and PAX2 IHC may facilitate the diagnosis of these tumors and should be included in the differential diagnostic IHC panel.

Comprehensive Immunophenotypic Characterization of Adult and Fetal Testes, the Excretory Duct System, and Testicular and Epididymal Appendages

“…[3][4][5][6][8][9][10][11][12][13] GC expression of SALL4, in contrast, is relatively decreased, but retained postnatally, with focal, weak staining in adult GC. 5,7 Our data also support prior studies demonstrating a lack of AR, ER, PAX8, WT1, calretinin, CK7, and CK20 in fetal and adult GC [14][15][16][17][18] and expand the set of negative GC markers to include PR, PSA, and PSMA.…”

“…5,19 Similarly, whereas our results confirm variable AR expression in adult SC, 14 we detected no significant ER expression in these cells. 15 Finally, our observations corroborate prior findings of negative IHC staining for PAX8, CK7, CK20, OCT4, SALL4, CD117, and PR in both fetal and adult SC, 5,10,16,18,20 and expand the set of negative SC markers to include PSA and PSMA.…”

“…1 As noted above, we found that adult RT consistently expresses CK7, PAX8, WT1, calretinin, and AR and shows variable expression of CK20 and ER; these data both confirm and expand the known RT IHC staining pattern. 5,[16][17][18][19][20][21] We also found that RT does not express PSA, PSMA, or CD117 and showed that the only significant difference between fetal and adult RT IHC staining is a lack of calretinin expression in fetal patients. The expression of WT1 and calretinin in adult RT is intriguing, given its possible sex cord derivation and our finding of strong and diffuse WT1 and calretinin staining in fetal SC.…”

“…2 We found that adult LC show strong and diffuse staining for calretinin only, despite prior reports of variable ER and CD117 expression. 5,11,[13][14][15][16][17][18] Furthermore, these cells do not express other examined IHC markers, including PSA, PSMA, and PR. Our data also indicate that fetal SC strongly and diffusely express WT1 and calretinin, an immunophenotype that is subsequently lost in adult SC, in contrast to prior studies.…”

Primary mediastinal seminomas: a comprehensive immunohistochemical study with a focus on novel markers

“…Although initial reports showed positive yet weak staining in 2 of 3 seminomas (15), more recent and substantially larger studies including series of 62 and 32 testicular seminomas, respectively, failed to identify any Pax8 staining in these tumors (14,37).…”