TY - JOUR
T1 - PD-L1 expression in endocervical adenocarcinoma correlation with patterns of tumor invasion, CD8+ tumor-infiltrating lymphocytes, and clinical outcomes
AU - Rivera-Colon, Glorimar
AU - Chen, Hao
AU - Molberg, Kyle
AU - Niu, Shuang
AU - Strickland, Amanda L.
AU - Castrillon, Diego H.
AU - Carrick, Kelley
AU - Gwin, Katja
AU - Lea, Jayanthi
AU - Zheng, Wenxin
AU - Lucas, Elena
N1 - Funding Information:
Conflicts of Interest and Source of Funding: Partially funded by the UT Southwestern Medical Center, Department of Pathology; intramural research fund of the Department of Pathology, UT Southwestern Medical Center to G.R.-C., Mark and Jane Gibson endowment fund, UT Southwestern Medical Center to W.Z., and Philip O’Bryan Montgomery endowment fund, UT Southwestern Medical Center to K.M. The authors have disclosed that they have no significant rela-tionships with, or financial interest in, any commercial companies pertaining to this article.
Funding Information:
The authors acknowledge the assistance of the University of Texas Southwestern Tissue Resource, a shared resource at the Simmons Comprehensive Cancer Center, which is supported in part by the National Cancer Institute under award number 5P30CA142543.
Publisher Copyright:
© 2020 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2021/6
Y1 - 2021/6
N2 - Programmed death-1 ligand (PD-L1) expression has been used as a predictive marker for response to immune checkpoint inhibitors and has been reported to have prognostic value. Its prevalence and significance in endocervical adenocarcinoma (ECA) remain underinvestigated. We evaluated PD-L1 expression and CD8+ tumor-infiltrating lymphocyte density in whole tissue sections of 89 ECAs. PD-L1 expression was observed in 68% of ECAs by combined positive score (CPS, cutoff 1) and 29% of ECAs by tumor proportion score (TPS, cutoff 1%). Using CPS, PD-L1 expression was seen in 11%, 78%, and 72% of pattern A, B, and C tumors, respectively, with significantly higher expression in tumors with destructive-type invasion (B and C) (P = 0.001 [A vs. B], 0.0006 [A vs. C], 0.0002 [A vs. B+C]). Using TPS, no significant difference in PDL1 expression was seen between tumors with different invasion patterns (0%, 22%, and 32% in tumors with pattern A, B, and C, respectively; P = 0.27 [A vs. B], 0.053 [A vs. C], 0.11 [A vs. B+C]). PD-L1-positive ECAs demonstrated significantly higher CD8+ tumor-infiltrating lymphocyte density (CPS: P = 0.028; TPS: P = 0.013) and worse progression-free survival when compared with PD-L1-negative ECAs (CPS: hazard ratio [HR] = 4.253 vs. 0.235, P = 0.025; TPS: HR = 4.98 vs. 0.2; P = 0.004). When invasion patterns were separately assessed, pattern C tumors similarly showed worse progression-free survival in PD-L1-positive tumors (CPS: HR = 6.15 vs. 0.16, P = 0.045; TPS: HR = 3.78 vs. 0.26, P = 0.027). In conclusion, our data show frequent PD-L1 expression in ECA with destructive-type invasion, supporting the role of the PD-1/PDL1 pathway as a therapeutic target for these tumors. Our data also support PD-L1 as a negative prognostic marker associated with a potentially unfavorable outcome.
AB - Programmed death-1 ligand (PD-L1) expression has been used as a predictive marker for response to immune checkpoint inhibitors and has been reported to have prognostic value. Its prevalence and significance in endocervical adenocarcinoma (ECA) remain underinvestigated. We evaluated PD-L1 expression and CD8+ tumor-infiltrating lymphocyte density in whole tissue sections of 89 ECAs. PD-L1 expression was observed in 68% of ECAs by combined positive score (CPS, cutoff 1) and 29% of ECAs by tumor proportion score (TPS, cutoff 1%). Using CPS, PD-L1 expression was seen in 11%, 78%, and 72% of pattern A, B, and C tumors, respectively, with significantly higher expression in tumors with destructive-type invasion (B and C) (P = 0.001 [A vs. B], 0.0006 [A vs. C], 0.0002 [A vs. B+C]). Using TPS, no significant difference in PDL1 expression was seen between tumors with different invasion patterns (0%, 22%, and 32% in tumors with pattern A, B, and C, respectively; P = 0.27 [A vs. B], 0.053 [A vs. C], 0.11 [A vs. B+C]). PD-L1-positive ECAs demonstrated significantly higher CD8+ tumor-infiltrating lymphocyte density (CPS: P = 0.028; TPS: P = 0.013) and worse progression-free survival when compared with PD-L1-negative ECAs (CPS: hazard ratio [HR] = 4.253 vs. 0.235, P = 0.025; TPS: HR = 4.98 vs. 0.2; P = 0.004). When invasion patterns were separately assessed, pattern C tumors similarly showed worse progression-free survival in PD-L1-positive tumors (CPS: HR = 6.15 vs. 0.16, P = 0.045; TPS: HR = 3.78 vs. 0.26, P = 0.027). In conclusion, our data show frequent PD-L1 expression in ECA with destructive-type invasion, supporting the role of the PD-1/PDL1 pathway as a therapeutic target for these tumors. Our data also support PD-L1 as a negative prognostic marker associated with a potentially unfavorable outcome.
KW - Cervical cancer
KW - Endocervical adenocarcinoma
KW - Invasion pattern
KW - PD-L1
KW - Survival
KW - Tumor-infiltrating lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=85097814310&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097814310&partnerID=8YFLogxK
U2 - 10.1097/PAS.0000000000001633
DO - 10.1097/PAS.0000000000001633
M3 - Article
C2 - 33298732
AN - SCOPUS:85097814310
SN - 0147-5185
VL - 45
SP - 742
EP - 752
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 6
ER -