title: Ki-67 antigen in lung neuroendocrine tumors: unraveling a role in clinical practice.
abstract: Classification of lung neuroendocrine (NE) tumors is a step-wise process with four tumor categories being identified by morphology, namely typical carcinoid (TC), atypical carcinoid, large-cell NE carcinoma, and small-cell lung carcinoma (SCLC). Ki-67 antigen or protein (henceforth simply Ki-67) has been largely studied in these tumors, but the clinical implications are so far not clear. A well-defined role has regarded the diagnostic use in the separation of TC and AC from SCLC in nonsurgical specimens, with monoclonal antibody MIB-1 resulting in the most used reagent after antigen retrieval procedures. Uncertainties, however, have arisen in its assessment, usually expressed as Ki-67 labeling index, because of some variability in obtaining either value of the fraction. A diagnostic role is currently lacking, even though there are significant differences in most cases between TC and AC, less so between large-cell NE carcinoma and SCLC. In addition, the prognostic role of Ki-67 is debated, likely due to methodological and biological reasons. The last challenge would be to identify an effective lung-specific grading system based on Ki-67 labeling index. In this review article, five relevant issues to Ki-67 have been addressed by using a question-answer methodology, with relevant key points discussing major interpretation issues. The conclusion is that Ki-67 is a feasible and potentially meaningful marker in lung NE tumors, but more data are needed to determine its ideal function in this setting of tumors.
authors: *Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; †Department of Biomedical and Clinical Sciences "Luigi Sacco," Università degli Studi, Milan, Italy; ‡Division of Anatomic Pathology, Gemelli Hospital and Università Cattolica del Sacro Cuore, Rome, Italy; §Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York; and ‖Division of Anatomic Pathology, San Luigi Gonzaga Hospital and University of Turin, Orbassano, Italy.
authors: Giuseppe
authors: G
authors: Pelosi
authors: Guido
authors: G
authors: Rindi
authors: William D
authors: WD
authors: Travis
authors: Mauro
authors: M
authors: Papotti
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D018358:Neuroendocrine Tumors / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy*; D017410:Practice Guidelines as Topic; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen