title: Ki-67 cytological index can distinguish well-differentiated from poorly differentiated pancreatic neuroendocrine tumors: a comparative cytohistological study of 53 cases.
abstract: The Ki-67 labeling index has been found to bear prognostic significance in gastrointestinal neuroendocrine tumors (NETs), and it was recently incorporated in NET histological grading. Nevertheless, a reliable preoperative determination of NET grading could be useful in clinical practice. The aim of this study is to compare the results of Ki-67 labeling index, as measured on cytological samples and on surgical specimens of patients with pancreatic NETs (P-NETs). We also investigated whether concordance might be improved, using a 5 % (instead of 2 %) cutoff value for defining G2 tumors. We retrospectively identified 48 consecutive patients with 53 P-NETs, from our five institutions, and we measured Ki-67 labeling index on their cytological samples and surgical specimens. The traditional 2 % and the alternative 5 % cutoff values were used to classify G2 tumors. The concordance rate between cytological and histological grading was 46/53 (86.8 %; weighted κ statistic 0.77; 95 % confidence interval (95 % CI) 0.60-0.94). No cases of cytological G1-G2 NETs were upgraded to G3 neuroendocrine carcinoma (NEC) at histological grading. Cytology was found to be highly specific in the diagnosis of both G2 (94.1 %; 95 % CI 80.3-99.3) and G3 tumors (100.0 %; 95 % CI 92.8-100), but the sensitivity was poor for G2 NETs (66.7 %; 95 % CI 38.4-88.2) and high for the prediction of G3 NECs (100 %; 95 % CI 39.8-100.0). When the 5 % cutoff value was adopted, concordance rate was 49/53 (92.4 %; weighted κ 0.82; 95 % CI 0.64-1.00). In conclusion, Ki-67 cytological expression can distinguish well-differentiated (both G1 and G2) from poorly differentiated P-NETs, and it may be useful for their preoperative classification.
authors.affiliation: Department of Pathology, Arcispedale Santa Maria Nuova-IRCCS, Viale Risorgimento 80, 42123, Reggio Emilia, Italy, carlinfante.gabriele@asmn.re.it.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Carlinfante
authors.forename: Paola
authors.initials: P
authors.lastname: Baccarini
authors.forename: Debora
authors.initials: D
authors.lastname: Berretti
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cassetti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cavina
authors.forename: Rita
authors.initials: R
authors.lastname: Conigliaro
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Pellegrin
authors.forename: Luca
authors.initials: L
authors.lastname: Di Tommaso
authors.forename: Carlo
authors.initials: C
authors.lastname: Fabbri
authors.forename: Adele
authors.initials: A
authors.lastname: Fornelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Frasoldati
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gardini
authors.forename: Luisa
authors.initials: L
authors.lastname: Losi
authors.forename: Livia
authors.initials: L
authors.lastname: Maccio
authors.forename: Raffaele
authors.initials: R
authors.lastname: Manta
authors.forename: Nico
authors.initials: N
authors.lastname: Pagano
authors.forename: Romano
authors.initials: R
authors.lastname: Sassatelli
authors.forename: Silvia
authors.initials: S
authors.lastname: Serra
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Camellini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018278:Carcinoma, Neuroendocrine / Q000473:pathology; D002454:Cell Differentiation; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen