Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients.
- Author:
Sung Joo KIM
1
;
Soyeon AN
;
Jae Hoon LEE
;
Joo Young KIM
;
Ki Byung SONG
;
Dae Wook HWANG
;
Song Cheol KIM
;
Eunsil YU
;
Seung Mo HONG
Author Information
- Publication Type:Original Article
- Keywords: Pancreas; Neuroendocrine tumors; Receptors, progesterone; Survival
- MeSH: Carcinogenesis*; Classification; Disease-Free Survival; Humans; Lymph Nodes; Multivariate Analysis; Neoplasm Metastasis; Neuroendocrine Tumors*; Pancreas; Pancreatic Neoplasms; Progesterone*; Prognosis; Receptors, Progesterone*; Survival Rate; Telomere; World Health Organization
- From:Journal of Pathology and Translational Medicine 2017;51(4):388-395
- CountryRepublic of Korea
- Language:English
- Abstract: 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.
