Abstract
The objective of this study was to investigate the relationship of insulin-like growth factor 2 (IGF2) expression and survival in women with uterine carcinosarcoma (UCS). Insulin-like growth factor 2 protein expression was determined by immunohistochemical staining of tumor tissues from 103 patients with UCS. The H-score (product of staining intensity and percentage positive cells) was quantified for the epithelial cytoplasmic (EC), epithelial nuclear (EN), and malignant stromal compartments. Multivariable Cox proportional hazard regression models were used to examine the relationship of IGF2 levels with progression-free survival (PFS) and overall survival (OS). Adjusting for stage, race, and adjuvant therapy, PFS and OS were reduced in patients with high IGF2 (H-score ≥ median) in the EC and EN compartments. Black race was independently associated with reduced PFS and OS in patients with early-stage disease, and IGF2 levels in the EC were higher in black than in white patients (P = 0.02, Wilcoxon test). In a race-stratified multivariable analysis, high IGF2 in the epithelial compartments more than doubled the risk of death in black women; HR = 2.43 (95% CI: 1.18–5.01, P = 0.02) for high IGF2 in the EC; and HR = 2.34 (95% CI: 1.25–4.39, P = 0.008) for high IGF2 in the EN. In conclusion, high tumor IGF2 expression is an independent risk factor for reduced PFS and OS in UCS. Black women have elevated tumor IGF2 compared with white women, and decreased survival associated with high IGF2. These findings identify IGF2 as a candidate biomarker for survival linked to racial disparity in women with UCS.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 616-625 |
| Number of pages | 10 |
| Journal | Cancer medicine |
| Volume | 7 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2018 |
Bibliographical note
Funding Information:This work was supported in part by the National Institutes of Health NIH Cancer Center Support Grant P30 CA013330, K12HD000849 and the American College of Obstetricians and Gynecologists Reproductive Scientist Development Program Award, and the American Association of Obstetricians and Gynecologists Foundation Bridge Award to G.S.H., and the National Institutes of Health 3P30CA013148-43S3, U10 CA180855, and K12HD001258-15 to C.A.L.
Funding Information:
This work was supported in part by the National Institutes of Health Cancer Center Support Grant P30 CA013330, NIH K12HD000849 and the American College of Obstetricians and Gynecologists Reproductive Scientist Development Program Award, and the American Association of Obstetricians and Gynecologists Foundation Bridge Award to G.S.H., and the National Institutes of Health 3P30CA013148-43S3, U10 CA180855, and K12HD001258-15 to C.A.L. The funders had no role in the study, in the collection, analysis, or interpretation of the data, in the writing of the manuscript, or in the decision to submit the manuscript for publication. We wish to thank Drs. Alessandro Santin and Jennifer Culhane for helpful comments.
Publisher Copyright:
© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
