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Nestin: A biomarker of aggressive uterine cancers
Erica R Hope1, Paulette Mhawech-Fauceglia2, Tanja Pejovic3
1Walter Reed National Military Medical Center, Department of Obstetrics and Gynecology, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States; Women's Health Integrated Research Center at Inova Health System, Department of Defense Gynecologic Cancer Center of Excellence, 3289 Woodburn Road, Suites 370 and 375, Annandale, VA 22003, United States.
Objective:
Evidence of potential prognostic and predictive value for nestin was investigated in well-annotated uterine cancers (UCs).
Methods:
Nestin expression and previously-published biomarkers were evaluated by immunohistochemistry (IHC) in UC tissue microarrays. Biomarkers were categorized as low vs. high, and nestin was cut at 10% positive staining. Relationship between nestin and clinicopathologic factors, biomarkers and outcome were evaluated using exact/log-rank testing or logistic/Cox modeling.
Results:
There were 323 eligible cases, 34% had advanced stage disease, 37% had type II disease, and 5% were carcinosarcomas. High nestin, observed in 19% of cases, was more common in advanced vs. early stage disease, type II cancers or uterine carcinosarcoma vs. type I cancers, grade 3 disease, positive lymphovascular space invasion (LVSI) and tumors >6cm (p<0.05). Nestin was inversely correlated with ER, PR and TFF3, and correlated with p53 and IMP3. Women with high vs. low nestin had worse progression-free survival (PFS) and cancer-specific survival overall, and worse PFS in the subset who received no adjuvant therapy or radiation, or had early stage, type I disease or tumors with both low and high ER, PR, TFF3, PTEN, p53 or IMP3. The relationship between nestin and PFS was independent of stage, LVSI and risk categorization but not type of UC.
Conclusions:
High nestin was more common in UCs with aggressive features and poor outcome. Nestin may represent a predictive biomarker for treatment selection for patients previously considered to be lower risk and a candidate for no or radiation-based adjuvant therapy, and compliment ER/PR testing.
