Presence of tumor-infiltrating lymphocytes is an independent prognostic factor in type I and II endometrial cancer.
OBJECTIVE
Presence of tumor-infiltrating lymphocytes (TIL) is of prognostic importance in a variety of malignancies. This study aims to determine the prognostic value of CD8(+) cytotoxic T-lymphocytes (CTL), FoxP3(+) regulatory T-lymphocytes (Treg) and CD45R0(+) memory T-lymphocytes in endometrial cancer.


METHODS
The number of tumor-infiltrating CD8(+), FoxP3(+), and CD45R0(+) T-lymphocytes was determined by immunohistochemistry on tissue microarrays containing tumor material from 368 FIGO stage I-IV endometrial cancer patients. Results from immunohistochemistry were correlated with clinicopathological parameters and survival.


RESULTS
High numbers of intra-tumoral CD8(+) T-lymphocytes, a high CD8(+)/FoxP3(+) ratio and the presence of CD45R0(+) T-lymphocytes were strongly associated with well-known favorable prognostic factors in endometrial cancer. Furthermore, high numbers of CD8(+) T-lymphocytes and a high CD8(+)/FoxP3(+) ratio were associated with a better disease free survival (DFS). High numbers of CD8(+) T-lymphocytes and the presence of CD45R0(+) T-lymphocytes were associated with a prolonged overall survival (OS). In multivariate analysis, high numbers of CD8(+) T-lymphocytes had an independent prognostic impact for overall survival in the entire cohort (HR 0.48, 95% C.I. 0.26-0.89, p=0.019) and in type II endometrial cancer (HR 0.17, 95% C.I. 0.08-0.36, p<0.001). A high CD8(+)/FoxP3(+) ratio was independently associated with improved survival in type I endometrial cancer (HR 0.44, 95% C.I. 0.23-0.84, p=0.013). CD45R0(+) lymphocytes were an independent factor for improved OS (HR 0.42, 95% C.I. 0.19-0.93, p=0.033).


CONCLUSIONS
This study shows that the presence of TIL is an independent prognostic factor in endometrial cancer and indicates an important role for the immune system in endometrial cancer.
Department of Gynecologic Oncology, University Medical Center Groningen, PO 30.001, 9700 RB Groningen, The Netherlands.
R A
RA
de Jong
N
N
Leffers
H M
HM
Boezen
K A
KA
ten Hoor
A G J
AG
van der Zee
H
H
Hollema
H W
HW
Nijman
D015703:Antigens, CD / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D016889:Endometrial Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000276:immunology; D008197:Lymph Node Excision; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology*; D046228:Microarray Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D017741:Survivors; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D015703:Antigens, CD; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D017493:Leukocyte Common Antigens