Combined Progesterone Receptor and PTEN Expression Predicts Metastasis and Survival in Patients with Pancreatic Neuroendocrine Tumors
Jeannelyn S Estrella, Russell Broaddus, James C Yao, Huamin Wang, Asif Rashid. U.T. M.D. Anderson Cancer Center, Houston, TX
Background: Lack of progesterone receptor (PR) expression has been shown to be associated with worse prognosis in pancreatic neuroendocrine tumors (PNETs). For endometrial and breast carcinoma, lack of PR expression is associated with loss of PTEN expression. This association and its utility to predict metastatic potential and survival have not been studied in low and intermediate grade PNETs.
Design: 104 resected PNETs (52 low and 52 intermediate grade) were analyzed for PR and PTEN immunohistochemical expression. PR stain was scored as positive or negative using <5% as cut-off. Tumors with reduced PTEN expression exhibited diffuse faint staining compared with strong staining of stromal cells (internal positive control). None of the tumors demonstrated complete loss of PTEN expression. Combined PR and PTEN expression was correlated with distant metastasis and overall survival using chi-squared and Kaplan-Meier analyses.
Results: 36 of 104 (35%) patients had distant metastasis at diagnosis. Among the remaining 68 patients with stage 1 and 2 disease, 8 (12%) developed distant metastasis at last follow-up. 12 (12%) patients had combined PR negative-PTEN reduced, 26 (25%) had either PR negative-PTEN strong or PR positive-PTEN reduced, and 66 (64%) had PR positive-PTEN strong PNETs. 8 of 11 patients (73%) with PR negative-PTEN reduced PNETs presented with distant metastasis compared to 15 of 64 patients (23%) with PR positive-PTEN strong PNETs (p=0.002). The combination of positive PR and strong PTEN expression was significantly associated with prolonged time to distant metastasis (p=0.034, Figure 1) and improved overall survival (p<0.001, Figure 2).
Conclusions: Immunohistochemical assessment of PR and PTEN can help identify a subset of PNETs with clinically aggressive behavior. These patients may be candidates for therapeutic approaches.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 249, Wednesday Morning