The use of lymph vessel markers to predict endometrial cancer outcome.
OBJECTIVE
To evaluate lymphangiogenesis and lymph vessel space involvement in different subsets of endometrial cancer using podoplanin, a specific marker for lymphatic endothelium.


METHODS
Sixty-two patients undergoing a hysterectomy with lymphadenectomy were included. Distribution of histopathologic subtypes was as follows: 30 endometrioid (48%), 18 serous (29%), 9 clear cell carcinoma (15%), and 5 carcinosarcomas (8%). Distribution of surgical stage according to the International Federation of Gynecology and Obstetrics 2009 criteria was as follows: 33 stage I (53%), 7 stage II (11%), 1 stage IIIA (2%), 15 stage IIIC1 (24%), and 6 stage IIIC2 (10%). Tumor samples were immunostained for podoplanin and the panendothelial marker, CD31. Peritumoral and intratumoral blood vessel density and lymph vessel density were assessed using an image analysis system that calculated mean vessel cross-sectional area (in micrometer squared) and vessel density (per millimeter squared). Presence of blood vessel space involvement and lymph vessel space involvement was screened for. The findings were linked with clinical outcome using Cox regression.


RESULTS
Twenty-one patients (34%) experienced recurrence, and 13 (21%) died of disease. Univariate analysis showed that blood vessel space involvement was related to worse overall survival (hazard ratio, 6.59; 95% confidence interval, 1.30-120). Multivariate analyses confirmed the prognostic importance of this variable for overall survival (hazard ratio, 7.52; 95% confidence interval, 1.32-144).


CONCLUSIONS
Blood vessel space involvement is a prognostic marker for worse survival. Although lymph vessels were stained with the most reliable marker, podoplanin, lymph vessel density and lymphovascular space involvement do not seem to be of prognostic importance.
Vandenput
Ingrid
I
Leuven Cancer Institute, Gynecologic Oncology, UZ Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium.
Vanhove
Thomas
T
Calster
Ben Van
BV
Gorp
Toon Van
TV
Moerman
Philippe
P
Verbist
Godelieve
G
Vergote
Ignace
I
Amant
Frédéric
F
D018262:Adenocarcinoma, Clear Cell / Q000175:diagnosis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002296:Carcinosarcoma / Q000175:diagnosis / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D007124:Immunoenzyme Techniques; D008197:Lymph Node Excision; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009367:Neoplasm Staging; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011379:Prognosis; D000098853:Podoplanin
D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C117468:PDPN protein, human; D000098853:Podoplanin