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Background: Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients. Methods: To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival. Results: PR expression was gradually decreased from normal islets (49/49 cases, 100%) to neuroendocrine microadenoma (14/21, 66.6%) to PanNETs (60/277, 21.3%; p < .001). PanNETs with loss of PR expression were associated with increased tumor size (p < .001), World Health Organization grade (p = .001), pT classification (p < .001), perineural invasion (p = .028), lymph node metastasis (p = .004), activation of alternative lengthening of telomeres (p = .005), other peptide hormonal expression (p < .001) and ATRX/DAXX expression (p = .015). PanNET patients with loss of PR expression (5-year survival rate, 64.1%) had significantly poorer recurrence-free survival outcomes than those with intact PR expression (90%) by univariate (p = .012) but not multivariate analyses. Similarly, PanNET patients with PR expression loss (5-year survival rate, 76%) had significantly poorer overall survival by univariate (p = .015) but not multivariate analyses. Conclusions: Loss of PR expression was noted in neuroendocrine microadenomas and was observed in the majority of PanNETs. This was associated with increased grade, tumor size, and advanced pT and pN classification; and was correlated with decreased patient survival time by univariate but not multivariate analyses. Loss of PR expression can provide additional information on shorter disease-free survival in PanNET patients.
Key Words: Pancreas; Neuroendocrine tumors; Receptors, progesterone; Survival
Pancreatic neuroendocrine tumors (PanNETs) are rare, amounting to only 3% of pancreatic neoplasms1,2 and 9% of all gastroenteropancreatic neuroendocrine tumors in Korea.3 Although PanNET patients have better survival outcomes than pancreatic ductal adenocarcinoma patients, PanNETs are still malignant neoplasms with a 10-year survival rate of only 40%50% after surgical resection.4-6 Surgical resection is the main curative treatment option for PanNET patients, although other therapies with somatostatin analogs, cytotoxic chemotherapies, and molecular targeted therapies have recently been used in metastatic or unresectable PanNET patients.7,8
A better understanding of the molecular mechanisms of PanNETs is important to better...