TY - JOUR
T1 - Specific Biomarker Expression Patterns in the Diagnosis of Residual and Recurrent Endometrial Precancers after Progestin Treatment
T2 - A Longitudinal Study
AU - Chen, Hao
AU - Lucas, Elena
AU - Strickland, Amanda L.
AU - Carrick, Kelley
AU - Gwin, Katja
AU - Castrillon, Diego H.
AU - Rivera-Colon, Glorimar
AU - Niu, Shuang
AU - Molberg, Kyle H.
AU - Zheng, Wenxin
N1 - Funding Information:
Conflicts of Interest and Source of Funding: Supported in part by the start-up fund and intramural research fund of the Department of Pathology to H.C., Philip O’Bryan Montgomery endowment fund to K.H.M., and Mark and Jane Gibson Endowment fund to W.Z., University of Texas Southwestern Medical Center. The remaining authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
Publisher Copyright:
© 2020 Lippincott Williams and Wilkins. All rights reserved.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Background:Conservative management with progestin is a treatment option for atypical hyperplasia (AH). However, pathologic diagnosis of residual/recurrent lesions is often problematic because of the profound morphologic changes induced by progestin and the lack of established diagnostic criteria for progestin-treated residual AH.Methods:We conducted a longitudinal study of 265 endometrial biopsies from 54 patients with a history of AH on progestin therapy. Patient outcomes were divided into 3 categories after morphologic review and immunohistochemical staining with phosphatase and tensin homolog (PTEN) and paired box 2 (PAX2): (1) persistent or residual disease; (2) recurrent disease; (3) complete response. All specimens were classified into 3 categories based on morphology: (1) persistent/recurrent disease (nonresponse), (2) morphologically uncertain response, (3) optimally treated (complete response). The staining patterns of PTEN/PAX2 were tracked over time in individual patients and correlated with morphologic findings before and after progestin therapy.Results:Our data showed that aberrant expression patterns of PTEN and/or PAX2 were identified in 48 (88.9%) of the 54 primary biopsies and persisted in persistent/recurrent AH across serial endometrial biopsies (n=99, P<0.00001), while normal PTEN and PAX2 expressions were consistently observed in optimally treated cases (n=84, P<0.00001). More importantly, follow-up biopsies that showed a morphologically uncertain response but a PTEN/PAX2 expression pattern identical to the initial biopsy were significantly correlated with persistent or recurrent disease (n=18, P=0.000182), as evidenced by areas with morphologic features diagnostic of AH on subsequent biopsy.Conclusions:Biomarker PTEN/PAX2 signatures offer a valuable diagnostic aid to identify residual AH in progestin-treated endometrial samples for which the biomarker status from preprogestin treated AH is known. The findings of this study are promising for a possible future change of diagnostic practice.
AB - Background:Conservative management with progestin is a treatment option for atypical hyperplasia (AH). However, pathologic diagnosis of residual/recurrent lesions is often problematic because of the profound morphologic changes induced by progestin and the lack of established diagnostic criteria for progestin-treated residual AH.Methods:We conducted a longitudinal study of 265 endometrial biopsies from 54 patients with a history of AH on progestin therapy. Patient outcomes were divided into 3 categories after morphologic review and immunohistochemical staining with phosphatase and tensin homolog (PTEN) and paired box 2 (PAX2): (1) persistent or residual disease; (2) recurrent disease; (3) complete response. All specimens were classified into 3 categories based on morphology: (1) persistent/recurrent disease (nonresponse), (2) morphologically uncertain response, (3) optimally treated (complete response). The staining patterns of PTEN/PAX2 were tracked over time in individual patients and correlated with morphologic findings before and after progestin therapy.Results:Our data showed that aberrant expression patterns of PTEN and/or PAX2 were identified in 48 (88.9%) of the 54 primary biopsies and persisted in persistent/recurrent AH across serial endometrial biopsies (n=99, P<0.00001), while normal PTEN and PAX2 expressions were consistently observed in optimally treated cases (n=84, P<0.00001). More importantly, follow-up biopsies that showed a morphologically uncertain response but a PTEN/PAX2 expression pattern identical to the initial biopsy were significantly correlated with persistent or recurrent disease (n=18, P=0.000182), as evidenced by areas with morphologic features diagnostic of AH on subsequent biopsy.Conclusions:Biomarker PTEN/PAX2 signatures offer a valuable diagnostic aid to identify residual AH in progestin-treated endometrial samples for which the biomarker status from preprogestin treated AH is known. The findings of this study are promising for a possible future change of diagnostic practice.
KW - atypical endometrial hyperplasia
KW - endometrial precancer
KW - endometrioid intraepithelial neoplasia
KW - progestin treatment
KW - recurrent hyperplasia after progestin therapy
KW - residual hyperplasia after progestin treatment
UR - http://www.scopus.com/inward/record.url?scp=85091054650&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85091054650&partnerID=8YFLogxK
U2 - 10.1097/PAS.0000000000001537
DO - 10.1097/PAS.0000000000001537
M3 - Article
C2 - 32931681
AN - SCOPUS:85091054650
SN - 0147-5185
VL - 44
SP - 1429
EP - 1439
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 10
ER -