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Review
. 2021 Mar 12;13(6):1247.
doi: 10.3390/cancers13061247.

Neuroendocrine Carcinomas with Atypical Proliferation Index and Clinical Behavior: A Systematic Review

Tiziana Feola  1   2 , Roberta Centello  1 , Franz Sesti  1 , Giulia Puliani  1   3 , Monica Verrico  4 , Valentina Di Vito  1 , Cira Di Gioia  4 , Oreste Bagni  5 , Andrea Lenzi  1 , Andrea M Isidori  1 , Elisa Giannetta  1 , Antongiulio Faggiano  6
Affiliations
Review

Neuroendocrine Carcinomas with Atypical Proliferation Index and Clinical Behavior: A Systematic Review

Tiziana Feola et al. Cancers (Basel). .

Abstract

Background: Highly proliferative (G3) neuroendocrine neoplasms are divided into well differentiated tumors (NETs) and poorly differentiated carcinomas (NECs), based on the morphological appearance. This systematic review aims to evaluate the clinicopathological features and the treatment response of the NEC subgroup with a Ki67 labeling index (LI) < 55%.

Methods: A literature search was performed using MEDLINE, Cochrane Library, and Scopus between December 2019 and April 2020, last update in October 2020. We included studies reporting data on the clinicopathological characteristics, survival, and/or therapy efficacy of patients with NECs, in which the Ki67 LI was specified.

Results: 8 papers were included, on a total of 268 NEC affected patients. NECs with a Ki67 LI < 55% have been reported in patients of both sexes, mainly of sixth decade, pancreatic origin, and large-cell morphology. The prevalent treatment choice was chemotherapy, followed by surgery and, in only one study, peptide receptor radionuclide therapy. The subgroup of patients with NEC with a Ki67 LI < 55% showed longer overall survival and progression free survival and higher response rates than the subgroup of patients with a tumor with higher Ki67 LI (≥55%).

Conclusions: NECs are heterogeneous tumors. The subgroup with a Ki67 LI < 55% has a better prognosis and should be treated and monitored differently from NECs with a Ki67 LI ≥ 55%.

Keywords: Ki67 labeling index; Ki67 proliferation index; neuroendocrine carcinoma; neuroendocrine neoplasm.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Current World Health Organization (WHO) gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) classification based on both cell morphology and Ki67 labelling index (LI). G1 neuroendocrine tumor (NET): a well-differentiated (WD) tumor characterized by a mitotic count <2/10 high power fields (HPFs) and/or a Ki67 LI <3%; G2 NET: a WD tumor characterized by a mitotic count 2–20/10 HPFs and/or a Ki67 LI 3–20%; G3 NET: a WD tumor characterized by a mitotic count >20/10 HPFs and/or a Ki67 LI >20%; G3 neuroendocrine carcinoma (NEC): a poorly-differentiated (PD) tumor characterized by a mitotic count >20/10 HPFs and/or a Ki67 LI >20%. As recent literature data suggested, NECs could be further subdivided into two distinct prognostic categories based on the Ki67 LI cut-off of 55%.
Figure 2
Figure 2
Flow-chart of the literature eligibility assessment process.
See this image and copyright information in PMC

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