title: Impact of the tumor microenvironment in predicting postoperative hepatic recurrence of pancreatic neuroendocrine tumors.
abstract: The disease frequency of pancreatic neuroendocrine tumors (PNETs) has been growing, and postoperative hepatic recurrence (PHR) is one of the factors affecting patient prognosis. The present study aimed to investigate biomarkers of PNETs in the primary disease site to predict PHR using immunohistochemical analysis for tumor-infiltrating lymphocytes (TILs: CD3, CD8 and CD45RO), human leukocyte antigen (HLA) class I, α-thalassemia/mental retardation X-linked (ATRX), death domain-associated protein (DAXX), mammalian target of rapamycin (mTOR) and phospho-mTOR (p-mTOR). Correlations were analyzed between TILs and the biomarkers, clinicopathological features and prognosis. Sixteen patients with PNETs who underwent radical surgery at our hospital were reviewed. We analyzed the correlation between PHR and immunohistochemical characteristics, and also between disease-free survival (DFS) or overall survival (OS) and the immunohistochemical characteristics. We found that PHR was associated with the expression patterns of DAXX and p-mTOR. No association was found between PHR and patient background, TILs or other biomarkers. DFS was found to be associated with ATRX, DAXX and p-mTOR. OS was associated only with p-mTOR. In conclusion, ATRX, DAXX and p-mTOR are useful molecular biomarkers for predicting PHR in patients who undergo radical surgery for PNETs. Use of these biomarkers will enable earlier decisions on which patients may benefit from adjuvant therapy.
authors.affiliation: Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Shoki
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tsuchikawa
authors.affiliation: Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Nagato
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Tamoto
authors.affiliation: Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Okamura
authors.affiliation: Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shichinohe
authors.affiliation: Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-0815, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirano
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D056970:Co-Repressor Proteins; D004265:DNA Helicases / Q000096:biosynthesis; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D009687:Nuclear Proteins / Q000096:biosynthesis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D011184:Postoperative Period; D011379:Prognosis; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis; D059016:Tumor Microenvironment / Q000235:genetics; D000075924:X-linked Nuclear Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein