The prognostic significance of the triple negative phenotype in endometrial cancer.
OBJECTIVE
To determine if the triple negative phenotype (TNP) has prognostic significance in endometrial cancer with respect to various surgicopathologic outcomes and survival.


METHODS
A tissue microarray was constructed of 396 endometrial cancers from patients who underwent surgical staging at the Ohio State University Medical Center. Immunohistochemistry was used to test for estrogen receptor, progesterone receptor, and HER2 expression. Fluorescent in-situ hybridization (FISH) was also used to test for HER2 amplification. TNP negative patients served as controls. Pearson's chi-square was used to evaluate the association of the TNP with variables associated with a poor prognosis. Cox proportional hazards model was used to perform univariate and multivariate analyses. Progression free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier curves, and the log rank test was used to compare the groups.


RESULTS
Twenty-seven percent of patients had the TNP. The TNP was associated with lymph node metastasis, myometrial invasion (>50%), high grade disease, non-endometrioid histology, and advanced staged disease (p<0.023 for lymph node metastasis and p<0.0001 for all others). The TNP was associated with a significantly worse survival, including a decreased PFS (p=0.009) and OS (p=0.01), but not in a fashion independent of other prognostic variables.


CONCLUSIONS
The TNP is associated with advanced stage, high grade, and high risk histology, as well as poor survival. Continued investigation of the exploitation of this phenotype with targeted therapies is necessary.
Kothari
Rajul
R
Division of Gynecologic Oncology, University of Minnesota Medical Center, 420 Delaware Street SE, Minneapolis, MN 55455, USA. koth0050@umn.edu
Morrison
Carl
C
Richardson
Debra
D
Seward
Shelly
S
O'Malley
David
D
Copeland
Larry
L
Fowler
Jeffrey
J
Cohn
David E
DE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D015996:Survival Rate; D055815:Young Adult
D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone