title: Ki-67 labeling index of neuroendocrine tumors of the lung has a high level of correspondence between biopsy samples and surgical specimens when strict counting guidelines are applied.
abstract: Optimal histopathological analysis of biopsies from metastases of neuroendocrine tumor (NET) of the lung requires more than morphology only. Additional parameters such as Ki-67 labeling index are required for adequate diagnosis, but few studies have compared reproducibility of different counting protocols and modalities of reporting on biopsies of lung NET. We compared the results of four different manual counting techniques to establish Ki-67 LI. On 47 paired biopsies and surgical specimens from 22 typical carcinoids (TCs), 14 atypical carcinoids (ACs), six large cell neuroendocrine carcinomas (LCNECs), and five small cell carcinomas (SCCs) immunohistochemical staining of Ki-67 antigen was performed. We counted, in regions of highest nuclear staining (HSR), a full ×40-high-power field (diameter = 0.55 mm), 500 or 2000 cells, or 2 mm2surface area, including the HSR or the entire biopsy fragment(s). Mitoses and necrosis were evaluated in an area of 2 mm2or the entire biopsy fragment(s). Between the four counting methods, no differences in Ki-67 LI were observed. However, a Ki-67 LI higher than 5% was found in only four cases when in an HSR, 500 cells were counted (18%), five (23%) when in an HSR 2000 cells were counted, four (18%) when 2 mm2were counted, and one (5%) TC case when the entire biopsy was counted. A 20% cutoff distinguished TC and AC from LCNEC and SCC with 100% specificity and sensitivity, while mitoses and necrosis failed to a large extent. Ki-67 LI in biopsy samples was concordant with that in resection specimens when 2000 cells, 2 mm2, or the entire biopsy fragment(s) were counted. Our results are important for clinical management of patients with metastases of a lung NET.
authors.affiliation: Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabbri
authors.affiliation: Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Cossa
authors.affiliation: Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Angelica
authors.initials: A
authors.lastname: Sonzogni
authors.affiliation: Department of Oncology, University of Turin, Turin, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
authors.affiliation: Department of Oncology, University of Turin, Turin, Italy.
authors.forename: Luisella
authors.initials: L
authors.lastname: Righi
authors.affiliation: Department of Oncology, University of Turin, Turin, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Gatti
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
authors.forename: Patrick
authors.initials: P
authors.lastname: Maisonneuve
authors.affiliation: Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Valeri
authors.affiliation: Division of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Pastorino
authors.affiliation: Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. giuseppe.pelosi@unimi.it.|Department of Oncology and Hemato-oncology, Università degli Studi, Milan, Italy. giuseppe.pelosi@unimi.it.|Dipartimento di Oncologia ed Emato-oncologia, Via Festa del Perdono, 7, I-20122, Milan, Italy. giuseppe.pelosi@unimi.it.
authors.forename: Giuseppe
authors.identifier: http://orcid.org/0000-0003-4725-4692
authors.initials: G
authors.lastname: Pelosi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D017410:Practice Guidelines as Topic; D015203:Reproducibility of Results; D012189:Retrospective Studies
chemical_list: D019394:Ki-67 Antigen
keywords: Atypical; Carcinoid; Carcinoma; Cell; Immunohistochemistry; KI-67 antigen; Large; Lung; Methodology; Neuroendocrine; Small; Tumors; Typical