TY - JOUR
T1 - Morules But Not Squamous Differentiation are a Reliable Indicator of CTNNB1 (β-catenin) Mutations in Endometrial Carcinoma and Precancers
AU - Niu, Shuang
AU - Lucas, Elena
AU - Molberg, Kyle
AU - Strickland, Amanda
AU - Wang, Yan
AU - Carrick, Kelley
AU - Rivera-Colon, Glorimar
AU - Gwin, Katja
AU - Sorelle, Jeffrey A.
AU - Castrillon, Diego H.
AU - Zheng, Wenxin
AU - Chen, Hao
N1 - Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/10/1
Y1 - 2022/10/1
N2 - Although collectively regarded as "squamous differentiation (SD)" in endometrial endometrioid carcinoma (EEC) and atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN), morules (often referred to as "squamous morules") and true SD may represent two distinct phenomena. Here, we explored the distinction between morules versus SD and investigated the association of morules and SD with CTNNB1 mutations. A total of 270 cases of EEC and AH/EIN were studied, including EEC with (n=36) or without (n=36) morules and AH/EIN with (n=80) or without (n=118) morules. Cases were analyzed by immunohistochemistry and selected cases (n=20) by targeted next-generation sequencing panel. Near-perfect agreement was found between morules and glandular β-catenin nuclear staining in AH/EIN and EEC. A strong positive association was found between morules and glandular β-catenin nuclear staining (P<0.0001, Φ=0.59 in AH/EIN; P<0.0001, Φ=0.85 in EEC). There was no association between (1) morules and glandular PAX2 or PTEN aberrant expression or (2) SD and aberrant expression of β-catenin, PAX2 or PTEN (Φ=0.09, β-catenin; Φ=0.16, PAX2; Φ=0.13, PTEN). CTNNB1 mutations were identified in all 20 selected morule-containing cases (100%). Next-generation sequencing was performed on 2 (preprogestin and postprogestin treatment) biopsies from 1 patient, revealing identical mutational profile in morules and glands. In conclusion, (1) SD and morules are distinct biological phenomena; (2) the presence of morules, but not SD, is a reliable indicator of CTNNB1 mutations in EEC and AH/EIN. Our findings demonstrate that SD and morules are distinct biological phenomena. Since morules but not SD are associated with β-catenin mutations, the distinction is clinically relevant and should be included in diagnostic reports.
AB - Although collectively regarded as "squamous differentiation (SD)" in endometrial endometrioid carcinoma (EEC) and atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN), morules (often referred to as "squamous morules") and true SD may represent two distinct phenomena. Here, we explored the distinction between morules versus SD and investigated the association of morules and SD with CTNNB1 mutations. A total of 270 cases of EEC and AH/EIN were studied, including EEC with (n=36) or without (n=36) morules and AH/EIN with (n=80) or without (n=118) morules. Cases were analyzed by immunohistochemistry and selected cases (n=20) by targeted next-generation sequencing panel. Near-perfect agreement was found between morules and glandular β-catenin nuclear staining in AH/EIN and EEC. A strong positive association was found between morules and glandular β-catenin nuclear staining (P<0.0001, Φ=0.59 in AH/EIN; P<0.0001, Φ=0.85 in EEC). There was no association between (1) morules and glandular PAX2 or PTEN aberrant expression or (2) SD and aberrant expression of β-catenin, PAX2 or PTEN (Φ=0.09, β-catenin; Φ=0.16, PAX2; Φ=0.13, PTEN). CTNNB1 mutations were identified in all 20 selected morule-containing cases (100%). Next-generation sequencing was performed on 2 (preprogestin and postprogestin treatment) biopsies from 1 patient, revealing identical mutational profile in morules and glands. In conclusion, (1) SD and morules are distinct biological phenomena; (2) the presence of morules, but not SD, is a reliable indicator of CTNNB1 mutations in EEC and AH/EIN. Our findings demonstrate that SD and morules are distinct biological phenomena. Since morules but not SD are associated with β-catenin mutations, the distinction is clinically relevant and should be included in diagnostic reports.
KW - AH/EIN
KW - CTNNB1 (β-catenin) mutations
KW - endometrial endometrioid carcinoma
KW - morules
KW - squamous differentiation
UR - http://www.scopus.com/inward/record.url?scp=85138453264&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85138453264&partnerID=8YFLogxK
U2 - 10.1097/PAS.0000000000001934
DO - 10.1097/PAS.0000000000001934
M3 - Article
C2 - 35834400
AN - SCOPUS:85138453264
SN - 0147-5185
VL - 46
SP - 1447
EP - 1455
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 10
ER -