TY - JOUR
T1 - Defining Substantial Lymphovascular Space Invasion in Endometrial Cancer
AU - Peters, E.E.M.
AU - Leon-Castillo, A.
AU - Smit, V.T.H.B.M.
AU - Boennelycke, M.
AU - Hogdall, E.
AU - Hogdall, C.
AU - Creutzberg, C.
AU - Jurgenliemk-Schulz, I.M.
AU - Jobsen, J.J.
AU - Mens, J.W.M.
AU - Lutgens, L.C.H.W.
AU - Van der Steen-Banasik, E.M.
AU - Ortoft, G.
AU - Bosse, T.
AU - Nout, R.
N1 - Funding Information:
The authors thank Curtis F. Barrett, PhD of English Editing Solutions, Bunnik, The Netherlands for providing medical editorial support, which was funded by Leiden University Medical Center, Leiden, The Netherlands. The PORTEC-1 study was supported by a grant from the Dutch Cancer Society (CKVO 90-01). The PORTEC-2 study was supported by a grant from the Dutch Cancer Society (CKTO 2001–04).
Funding Information:
R.N. reports grants by the Dutch Cancer Society, Dutch Research Council, Elekta, Varian and Accuracy, all unrelated to this work. C.C. reports grants by the Dutch Cancer Society. The remaining authors declare no conflict of interest.
Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Lymphovascular space invasion (LVSI) occurs in a minority of endometrial cancer (EC) cases, and the extent of LVSI is an important risk factor for recurrence and/or metastases. Our aim was to improve the reproducibility of measuring clinically meaningful LVSI by performing a quantitative analysis of the correlation between LVSI and the risk of pelvic lymph node recurrence in EC. EC samples from PORTEC-1 and PORTEC-2 trials were retrieved and used to collect quantitative data, including the number of LVSI-positive vessels per H&E-stained slide. Using a predefined threshold for clinical relevance, the risk of pelvic lymph node recurrence risk was calculated (Kaplan-Meier method, with Cox regression) using a stepwise adjustment for the number of LVSI-positive vessels. This analysis was then repeated in the Danish Gynecological Cancer Database (DGCD) cohort. Among patients in PORTEC-1 and PORTEC-2 trials who did not receive external beam radiotherapy, the 5-yr pelvic lymph node recurrence risk was 3.3%, 6.7% (P=0.51), and 26.3% (P<0.001), respectively when 0, 1 to 3, or >= 4 vessels had LVSI involvement; similar results were obtained for the DGCD cohort. Furthermore, both the average number of tumor cells in the largest embolus and the number of LVSI-positive H&E slides differed significantly between focal LVSI and substantial LVSI. On the basis of these results, we propose a numeric threshold (>= 4 LVSI-involved vessels in at least one H&E slide) for defining clinically relevant LVSI in EC, thereby adding supportive data to the semiquantitative approach. This will help guide gynecologic pathologists to differentiate between focal and substantial LVSI, especially in borderline cases.
AB - Lymphovascular space invasion (LVSI) occurs in a minority of endometrial cancer (EC) cases, and the extent of LVSI is an important risk factor for recurrence and/or metastases. Our aim was to improve the reproducibility of measuring clinically meaningful LVSI by performing a quantitative analysis of the correlation between LVSI and the risk of pelvic lymph node recurrence in EC. EC samples from PORTEC-1 and PORTEC-2 trials were retrieved and used to collect quantitative data, including the number of LVSI-positive vessels per H&E-stained slide. Using a predefined threshold for clinical relevance, the risk of pelvic lymph node recurrence risk was calculated (Kaplan-Meier method, with Cox regression) using a stepwise adjustment for the number of LVSI-positive vessels. This analysis was then repeated in the Danish Gynecological Cancer Database (DGCD) cohort. Among patients in PORTEC-1 and PORTEC-2 trials who did not receive external beam radiotherapy, the 5-yr pelvic lymph node recurrence risk was 3.3%, 6.7% (P=0.51), and 26.3% (P<0.001), respectively when 0, 1 to 3, or >= 4 vessels had LVSI involvement; similar results were obtained for the DGCD cohort. Furthermore, both the average number of tumor cells in the largest embolus and the number of LVSI-positive H&E slides differed significantly between focal LVSI and substantial LVSI. On the basis of these results, we propose a numeric threshold (>= 4 LVSI-involved vessels in at least one H&E slide) for defining clinically relevant LVSI in EC, thereby adding supportive data to the semiquantitative approach. This will help guide gynecologic pathologists to differentiate between focal and substantial LVSI, especially in borderline cases.
KW - Lymphovascular space invasion
KW - Substantial LVSI
KW - Endometrial carcinoma
KW - Threshold
KW - LVSI definition
KW - RISK-FACTORS
KW - STAGE-I
KW - RADIOTHERAPY
KW - CARCINOMA
KW - SURGERY
U2 - 10.1097/PGP.0000000000000806
DO - 10.1097/PGP.0000000000000806
M3 - Article
C2 - 34261899
SN - 0277-1691
VL - 41
SP - 220
EP - 226
JO - International Journal of Gynecological Pathology
JF - International Journal of Gynecological Pathology
IS - 3
ER -