GREB1 Protein Expression Is Associated With Low Recurrence Risk On Stage I Endometrioid Endometrial Carcinoma

Claudia CHAVES, Brazilian National Camcer Institute, Brazil
SIMAO T. 5 , NICOLAU-NETO P. 2 , SANTOS P. 2 , LISBOA L. 5 , MOREIRA F. 4 , BIANCCHI B. 4 , MOREIRA M. 3 , BESSA C. 1

1 Gynecologic Oncology Department, Brazilian National Cancer Institute, Rio de Janeiro, Brazil
2 Molecular Carcinogenesis Program, Brazilian National Cancer Institute, Rio de Janeiro, Brazi
3 Department of Genetics, Brazilian National Cancer Institute, Rio de Janeiro, Brazi
4 Pathology Department, Brazilian National Cancer Institute, Rio de Janeiro, Brazi
5 Biochemistry Department, IBRAG, Rio de Janeiro State University, Rio de Janeiro, Brazi

Purposes: Endometriod endometrial carcinoma (EEC) is usually diagnosed in early stages and has a favorable prognosis. However, some cases may present unexpected relapse with poor responsiveness to treatment. A previous DNA microarray assessment was performed with stage I EEC tumors, comparing gene expression profile of recurrent and non-recurrent cases. GREB1 (Growth Regulation by Estrogen in Breast Cancer 1) overexpression showed significant association with relapse. Therefore, the purpose of this study was to evaluate GREB1 protein expression on stage I EEC regarding recurrence status.
 
Methods: Clinicopathological features of 107 stage I EEC cases were collected, from which 35 presented recurrence and 72 had no relapse. GREB1 protein expression was assessed by immunohistochemistry (IHC) with the primary rabbit polyclonal antibody against GREB1 (N-13) (Santa Cruz Biotechnology, Inc®). The staining score evaluation was performed by two independent pathologists. Protein expression was considered positive when nuclear staining was greater than 10% and its results were compared to relapse status and other clinicopathological data. The chance of recurrence was calculated by Odds Ratio (OR).
 
Results: IHC revealed that GREB1 expression was found positive on 54 (50.5%) of 107 cases. Regarding non-recurrence group (n=72), it was positive in 42 (58.3%) cases; in 35 cases that presented relapse, it was positive in 12 (34.3%) (p=0.0196). No variables showed a significant association with GREB1 positive expression. However, women with low grade tumors had a higher chance of 2.7-fold to present positive GREB1 expression (p = 0.044). Crude and adjusted by age OR were calculated and both showed GREB1 positive expression conferred a protection association: positive GREB1 tumors provide 63% lower risk of relapse ocurrence comparing to negative tumors (OR = 0.37; p = 0.021).
 
Conclusion: positive GREB1 protein expression is associated with low recurrence risk on stage I EEC.
Funding: CNPq, FAPERJ, CAPES, MS.