Intraepithelial T cells and tumor proliferation: impact on the benefit from surgical cytoreduction in advanced serous ovarian cancer.
BACKGROUND
The aim of the study was to determine whether tumor-infiltrating lymphocytes and/or tumor mitotic activity could identify subgroups of patients with advanced serous epithelial ovarian cancer who would maximally benefit from aggressive surgical cytoreduction.


METHODS
Snap-frozen specimens from 134 consecutive patients with stage III or IV serous or poorly differentiated ovarian adenocarcinoma undergoing primary debulking surgery from a single US institution were characterized based on CD3(+), CD8(+), FoxP3(+) tumor-infiltrating lymphocytes, and Ki67 expression. Kaplan-Meier survival curves were estimated and compared using a log-rank statistic. A multivariate Cox model was used to estimate adjusted hazard ratios. Interactions were modeled using recursive partitioning based on maximal prognostic differentiation.


RESULTS
Brisk intraepithelial CD8(+) cells (P = .035) and low Ki67 expression (P = .042) portended prolonged survival. The T-cell infiltration was more likely to occur in tumors with high proliferation index. Patients whose tumors exhibited low Ki67 expression and high intraepithelial CD8(+) frequency had a 5-year survival rate of 73.3%. Patients with aggressive tumor behavior, that is, whose tumors exhibited low frequency of intraepithelial CD8(+) T cells or high Ki67 expression were more likely to draw benefit from aggressive surgical cytoreduction. Survival was similar for patients with brisk CD8(+) T cells who had optimal or suboptimal debulking. Likewise, survival was similar for patients with low Ki67 expression who had optimal or suboptimal debulking.


CONCLUSIONS
For the first time, these novel interactions of T cells, tumor proliferation index, and surgical treatment reveal that biological prognosticators may be useful for surgical decision making in ovarian cancer.
Adams
Sarah F
SF
Department of Obstetrics and Gynecology, Ovarian Cancer Research Center, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Levine
Douglas A
DA
Cadungog
Mark G
MG
Hammond
Rachel
R
Facciabene
Andrea
A
Olvera
Narciso
N
Rubin
Stephen C
SC
Boyd
Jeff
J
Gimotty
Phyllis A
PA
Coukos
George
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes; D049109:Cell Proliferation; D018293:Cystadenoma, Serous / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D011379:Prognosis; D013601:T-Lymphocytes; D016896:Treatment Outcome
D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D019394:Ki-67 Antigen