title: Prognostic Significance of Defining L-Cell Type on the Biologic Behavior of Rectal Neuroendocrine Tumors in Relation with Pathological Parameters.
abstract: In 2010, the World Health Organization categorized L-cell type neuroendocrine tumors (NETs) as tumors of uncertain malignancy, while all others were classified as malignant. However, the diagnostic necessity of L-cell immunophenotyping is unclear, as are tumor stage and grade that may guide diagnosis and management. To clarify the predictive markers of rectal neuroendocrine neoplasms (NENs), 5- and 10-year overall survival (OS) was analyzed by pathological parameters including L-cell phenotype.
  
  
  
  A total of 2,385 rectal NENs were analyzed from our previous multicenter study and a subset of 170 rectal NENs was immunophenotyped.
  
  
  
  In univariate survival analysis, tumor grade (p < 0.0001), extent (p < 0.0001), size (p < 0.0001), lymph node metastasis (p=0.0063), and L-cell phenotype (p < 0.0001) showed significant correlation with the prognosis of rectal NENs; however, none of these markers achieved independent significance in multivariate analysis. The 10-year OS of tumors of NET grade 1, < 10 mm, the mucosa/submucosa was 97.58%, 99.47%, and 99.03%, respectively. L-Cell marker, glucagon II (GLP-1&2), with a cut off score of > 10, is useful in defining L-Cell type. In this study, an L-cell immunophenotype was found in 83.5% of all rectal NENs and most, but not all L-cell type tumors were NET G1, small (< 10 mm) and confined to the mucosa/submucosa.
  
  
  
  From these results, the biological behavior of rectal NENs does not appear to be determined by L-cell type alone but instead by a combination of pathological parameters.
authors.affiliation: Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Sohn
authors.affiliation: Department of Pathology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Mee-Yon
authors.initials: MY
authors.lastname: Cho
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Yangsoon
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyunki
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Department of Pathology, Inha University Hospital, Inha University School of Medicine, Incheon, Korea.
authors.forename: Joon Mee
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Jung
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyoung-Mee
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Pathology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea.
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Chan
authors.affiliation: Department of Pathology, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea.
authors.forename: Do Youn
authors.initials: DY
authors.lastname: Park
authors.affiliation: Department of Pathology, Inje University Ilsan Paik Hospital, Inje Univeristy College of Medicine, Goyang, Korea.
authors.forename: Mee
authors.initials: M
authors.lastname: Joo
authors.affiliation: Department of Pathology, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Korea.
authors.forename: Sujin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Pathology, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Woo Sung
authors.initials: WS
authors.lastname: Moon
authors.affiliation: Department of Pathology, Inje University Busan Paik Hospital,Inje University College of Medicine, Busan, Korea.
authors.forename: Mi Seon
authors.initials: MS
authors.lastname: Kang
authors.affiliation: Department of Pathology, Soon Chun Hyang University Hospital, Soon Chun Hyang University College of Medicine, Seoul, Korea.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Jin
authors.affiliation: Department of Pathology, Inje University Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea.
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Kang
authors.affiliation: Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sun Och
authors.initials: SO
authors.lastname: Yoon
authors.affiliation: Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: HyeSeung
authors.initials: H
authors.lastname: Han
authors.affiliation: Division of Statistics in Institute of ifestyle Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: EunHee
authors.initials: E
authors.lastname: Choi
mesh_terms: D014408:Biomarkers, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping / Q000379:methods*; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors / Q000145:classification / Q000473:pathology*; D012004:Rectal Neoplasms / Q000145:classification / Q000473:pathology*; D056910:Republic of Korea; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor
keywords: Immunohistochemistry; International Classification of Diseases; L cells; Neuroendocrine tumors; Rectal neoplasms; Survival