TY - JOUR
T1 - Tubo-Ovarian Transitional Cell Carcinoma and High-grade Serous Carcinoma Show Subtly Different Immunohistochemistry Profiles
AU - Magrill, Jamie
AU - Karnezis, Anthony N.
AU - Tessier-Cloutier, Basile
AU - Talhouk, Aline
AU - Kommoss, Stefan
AU - Cochrane, Dawn
AU - Chow, Christine
AU - Cheng, Angela
AU - Soslow, Robert
AU - Hauptmann, Steffen
AU - du Bois, Andreas
AU - Pfisterer, Jacobus
AU - Gilks, C. Blake
AU - Huntsman, David G.
AU - Kommoss, Friedrich
N1 - Publisher Copyright:
© 2018 International Society of Gynecological Pathologists.
PY - 2019/11
Y1 - 2019/11
N2 - Tubo-ovarian transitional cell carcinoma (TCC) is grouped with high-grade serous carcinoma (HGSC) in the current World Health Organization classification. TCC is associated with BRCA mutations and a better prognosis compared with HGSC. Previous papers examining the immunohistochemical features of TCC have studied limited numbers of samples. No marker reflecting the biological difference between TCC and HGSC is known. We collected a large cohort of TCC to determine whether TCC and HGSC could be distinguished by immunohistochemistry. A tissue microarray was built from 89 TCC and a control cohort of 232 conventional HGSC. Immunohistochemistry was performed, scored, and statistically analyzed for routine markers of HGSC and urothelial tumors: PAX8, WT1, p53, p16, ER, p63, and GATA3. Using scoring cutoffs commonly employed in clinical practice, the immunohistochemical profile of TCC was indistinguishable from HGSC for all markers. However, more detailed scoring criteria revealed statistically significant differences between the 2 groups of tumors with respect to ER, PAX8, and WT1. HGSC showed more diffuse and intense staining for PAX8 (P=0.004 and 0.001, respectively) and WT1 (P=0.002 and 0.002, respectively); conversely, TCC showed more intense staining for ER (P=0.007). TCC and HGSC therefore show subtle differences in their immunohistochemical profiles which might reflect underlying (epi)genetic differences. Further studies using proteomic analysis will focus on the identification of differentially expressed proteins that might serve as markers of TCC-like differentiation, which could help explain biologic differences between TCC and HGSC and might identify other cases of HGSC with a better prognosis.
AB - Tubo-ovarian transitional cell carcinoma (TCC) is grouped with high-grade serous carcinoma (HGSC) in the current World Health Organization classification. TCC is associated with BRCA mutations and a better prognosis compared with HGSC. Previous papers examining the immunohistochemical features of TCC have studied limited numbers of samples. No marker reflecting the biological difference between TCC and HGSC is known. We collected a large cohort of TCC to determine whether TCC and HGSC could be distinguished by immunohistochemistry. A tissue microarray was built from 89 TCC and a control cohort of 232 conventional HGSC. Immunohistochemistry was performed, scored, and statistically analyzed for routine markers of HGSC and urothelial tumors: PAX8, WT1, p53, p16, ER, p63, and GATA3. Using scoring cutoffs commonly employed in clinical practice, the immunohistochemical profile of TCC was indistinguishable from HGSC for all markers. However, more detailed scoring criteria revealed statistically significant differences between the 2 groups of tumors with respect to ER, PAX8, and WT1. HGSC showed more diffuse and intense staining for PAX8 (P=0.004 and 0.001, respectively) and WT1 (P=0.002 and 0.002, respectively); conversely, TCC showed more intense staining for ER (P=0.007). TCC and HGSC therefore show subtle differences in their immunohistochemical profiles which might reflect underlying (epi)genetic differences. Further studies using proteomic analysis will focus on the identification of differentially expressed proteins that might serve as markers of TCC-like differentiation, which could help explain biologic differences between TCC and HGSC and might identify other cases of HGSC with a better prognosis.
KW - Ovarian cancer
KW - Transitional cell carcinoma
KW - High-grade serous carcinoma
KW - Immunohistochemistry
KW - Biomarkers
KW - OVARIAN-CARCINOMA
KW - UROTHELIAL DIFFERENTIATION
KW - PROSTATE ADENOCARCINOMA
KW - INVASION PATTERNS
KW - BRCA2 MUTATIONS
KW - BRENNER-TUMORS
KW - USEFUL MARKER
KW - T-CELLS
KW - EXPRESSION
KW - SURVIVAL
U2 - 10.1097/PGP.0000000000000538
DO - 10.1097/PGP.0000000000000538
M3 - Article
C2 - 30059451
SN - 0277-1691
VL - 38
SP - 552
EP - 561
JO - International Journal of Gynecological Pathology
JF - International Journal of Gynecological Pathology
IS - 6
ER -