title: Malignant ileocaecal serotonin-producing carcinoid tumours: the presence of a solid growth pattern and/or Ki67 index above 1% identifies patients with a poorer prognosis.
abstract: Patients with malignant serotonin-producing carcinoid tumours in the jejunum, ileum and caecum generally have long survival expectancy. In some patients, however, tumour progression is more rapid and there is a need to identify them at an early stage. The purpose of this study was to determine if histopathological characteristics and/or Ki67 and apoptotic indices are of prognostic value in cases of metastatic disease. Eighty-one patients with this tumour were included in the study; all had metastases and their survival range was 1-223 months. Five growth patterns were identified and described. For 57 patients whose tumour material was available, the Ki67 and apoptotic indices were calculated for ten randomly selected tumour areas and 'hot spots'. A Cox regression analysis was used to test if histopathology and/or Ki67 index >/=1% could identify patients whose survival might be shorter than anticipated. One of the histopathological growth patterns-the solid (non-organoid) cell pattern-was correlated to shorter survival in both primary tumours and metastases, when compared with the organoid growth patterns (hazard ratio 2.9 and 2.3, p</=0.01). In 75% of primary tumours and 67% of metastases, the average Ki67 index was<0.5%. Ki67 index in 'hot spots' ranged from 0.1 to 14%. Ki67 index >/=1%, in both primary tumour and metastases, identified patients at increased risk of shorter survival (hazard ratio 5.4 and 2.5, p</=0.01). The apoptotic index was very low in all cases. We conclude that in patients with metastazising serotonin-producing carcinoids, two independent criteria, a solid growth pattern and Ki67 index >/=1%, can be used to identify patients with a poorer prognosis. This study also showed that Ki67 index <2% cannot, as previously suggested, be used to indicate a benign progression for this tumour category.
authors.affiliation: Department of Medical Sciences, Section of Endocrine Oncology, Uppsala University, Sweden. janet.cunningham@medsci.uu.se
authors.forename: Janet L
authors.initials: JL
authors.lastname: Cunningham
authors.forename: Lars
authors.initials: L
authors.lastname: Grimelius
authors.forename: Anders
authors.initials: A
authors.lastname: Sundin
authors.forename: Smriti
authors.initials: S
authors.lastname: Agarwal
authors.forename: Eva T
authors.initials: ET
authors.lastname: Janson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002276:Carcinoid Tumor / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology*; D002430:Cecal Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D007078:Ileal Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology*; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D012701:Serotonin / Q000096:biosynthesis*; D013534:Survival; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D012701:Serotonin