State of the Art: Concise Review
Ki-67 Antigen in Lung Neuroendocrine Tumors: Unraveling a Role in Clinical Practice

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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.

Key Words

Ki-67
Antigen
MIB-1
Labeling index
Lung
Neuroendocrine
Carcinoid
Large-cell neuroendocrine carcinoma
Small-cell lung carcinoma
Diagnosis
Immunohistochemistry
Prognosis
Therapy

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Disclosure: The authors declare no conflict of interest.