L1CAM: amending the "low-risk" category in endometrial carcinoma.
OBJECTIVE
Low- and intermediate-risk endometrial carcinomas have an excellent prognosis. Nonetheless, a small subgroup of such patients will experience unexpected relapse. Recently L1CAM was suggested to be a strong prognosticator in endometrial carcinoma. The focus of our study was on low- and intermediate-risk disease, where no or only limited adjuvant treatment is recommended according to current guidelines.


METHODS
Endometrial carcinomas of low, intermediate and high-intermediate risk according to published 2016 consensus guidelines were identified. The study was limited to cases with previous central pathology review focusing on histotype, depth of myometrial invasion, presence of lymphovascular space invasion (LVSI) and MELF pattern of invasion. Standard L1CAM immunohistochemistry was performed. Disease-specific uni- and multivariate survival analyses were calculated.


RESULTS
A total of 344 cases were available for immunohistochemistry (low-risk: n = 250; intermediate-risk: n = 67; high-intermediate-risk: n = 27). L1CAM positivity rates were: 29/344 (8.4 %; all cases), 18/250 (7.2 %; low-risk), 6/67 (9.0 %; intermediate-risk) and 5/27 (18.5 %; high-intermediate-risk). Expression of L1CAM was independent of LVSI and MELF. L1CAM was a significant independent prognosticator for disease-specific survival with a hazard ratio of 5.98 [CI 1.50-22.14, p = 0.012]. Adverse prognostic significance of L1CAM positivity was maintained after low-risk subgroup analysis (5-year disease-specific survival rates 71.8 vs. 100 %, p < 0.0001). All four tumour-related deaths in the subgroup of low-risk disease occurred in patients with L1CAM-positive tumours.


CONCLUSIONS
The current definition of "low-risk" in endometrial carcinoma should be amended. "Low-risk carcinomas" should be limited to L1CAM-negative tumours. L1CAM status will play a key role in future algorithms to tailor adjuvant treatment and patient follow-up strategies.
Department für Frauengesundheit, Universitätsklinikum Tübingen, Calwerstr. 7, 72076, Tübingen, Germany.
Felix
F
Kommoss
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
Friedrich
F
Kommoss
Department für Frauengesundheit, Universitätsklinikum Tübingen, Calwerstr. 7, 72076, Tübingen, Germany.
Friederike
F
Grevenkamp
Department für Frauengesundheit, Universitätsklinikum Tübingen, Calwerstr. 7, 72076, Tübingen, Germany.
Anne-Kathrin
AK
Bunz
Department für Frauengesundheit, Universitätsklinikum Tübingen, Calwerstr. 7, 72076, Tübingen, Germany.
Florin-Andrei
FA
Taran
Institut für Pathologie, Universitätsklinikum Tübingen, Tübingen, Germany.
Falko
F
Fend
Department für Frauengesundheit, Universitätsklinikum Tübingen, Calwerstr. 7, 72076, Tübingen, Germany.
Sara Y
SY
Brucker
Department für Frauengesundheit, Universitätsklinikum Tübingen, Calwerstr. 7, 72076, Tübingen, Germany.
Diethelm
D
Wallwiener
Department für Frauengesundheit, Universitätsklinikum Tübingen, Calwerstr. 7, 72076, Tübingen, Germany.
Birgitt
B
Schönfisch
Institut für Pathologie, Universitätsklinikum Tübingen, Tübingen, Germany.
Karen
K
Greif
Institut für Pathologie, LKH Graz West, Graz, Austria.
Sigurd
S
Lax
Institut für Pathologie, Universitätsklinikum Tübingen, Tübingen, Germany.
Annette
A
Staebler
Department für Frauengesundheit, Universitätsklinikum Tübingen, Calwerstr. 7, 72076, Tübingen, Germany. stefan.kommoss@med.uni-tuebingen.de.
Stefan
S
Kommoss
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018269:Carcinoma, Endometrioid / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D012306:Risk
D014408:Biomarkers, Tumor; D039842:Neural Cell Adhesion Molecule L1
Endometrial carcinoma; L1CAM; Prognostic marker; Risk stratification
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