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Utility of KI-67 as a prognostic biomarker in pulmonary neuroendocrine neoplasms: a systematic review and meta-analysis

Utility of KI-67 as a prognostic biomarker in pulmonary neuroendocrine neoplasms: a systematic review and meta-analysis
Utility of KI-67 as a prognostic biomarker in pulmonary neuroendocrine neoplasms: a systematic review and meta-analysis

Objectives: Ki-67, a marker of cellular proliferation, is associated with prognosis across a wide range of tumours, including gastroenteropancreatic neuroendocrine neoplasms (NENs), lymphoma, urothelial tumours and breast carcinomas. Its omission from the classification system of pulmonary NENs is controversial. This systematic review sought to assess whether Ki-67 is a prognostic biomarker in lung NENs and, if feasible, proceed to a meta-analysis.

Research, design and methods: Medline (Ovid), Embase, Scopus and the Cochrane library were searched for studies published prior to 28 February 2019 and investigating the role of Ki-67 in lung NENs. Eligible studies were those that included more than 20 patients and provided details of survival outcomes, namely, HRs with CIs according to Ki-67 percentage. Studies not available as a full text or without an English manuscript were excluded. This study was prospectively registered with PROSPERO.

Results: of 11 814 records identified, seven studies met the inclusion criteria. These retrospective studies provided data for 1268 patients (693 TC, 281 AC, 94 large cell neuroendocrine carcinomas and 190 small cell lung carcinomas) and a meta-analysis was carried out to estimate a pooled effect. Random effects analyses demonstrated an association between a high Ki-67 index and poorer overall survival (HR of 2.02, 95% CI 1.16 to 3.52) and recurrence-free survival (HR 1.42; 95% CI 1.01 to 2.00).

Conclusion: this meta-analysis provides evidence that high Ki-67 labelling indices are associated with poor clinical outcomes for patients diagnosed with pulmonary NENs. This study is subject to inherent limitations, but it does provide valuable insights regarding the use of the biomarker Ki-67, in a rare tumour.

Prospero registration number: CRD42018093389.

endocrine tumours, pathology, respiratory tract tumours
2044-6055
e041961
Naheed, Salma
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Holden, Chloe
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Tanno, Lulu
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Pattini, Linda
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Pearce, Neil W
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Green, Bryan
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Jaynes, Eleanor
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Cave, Judith
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Ottensmeier, Christian H
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Pelosi, Giuseppe
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Naheed, Salma
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Holden, Chloe
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Tanno, Lulu
b1e0f618-9918-428a-88c7-52846c2b8a64
Pattini, Linda
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Pearce, Neil W
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Green, Bryan
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Jaynes, Eleanor
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Cave, Judith
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Ottensmeier, Christian H
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Pelosi, Giuseppe
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Naheed, Salma, Holden, Chloe, Tanno, Lulu, Pattini, Linda, Pearce, Neil W, Green, Bryan, Jaynes, Eleanor, Cave, Judith, Ottensmeier, Christian H and Pelosi, Giuseppe (2022) Utility of KI-67 as a prognostic biomarker in pulmonary neuroendocrine neoplasms: a systematic review and meta-analysis. BMJ Open, 12 (3), e041961. (doi:10.1136/bmjopen-2020-041961).

Record type: Article

Abstract

Objectives: Ki-67, a marker of cellular proliferation, is associated with prognosis across a wide range of tumours, including gastroenteropancreatic neuroendocrine neoplasms (NENs), lymphoma, urothelial tumours and breast carcinomas. Its omission from the classification system of pulmonary NENs is controversial. This systematic review sought to assess whether Ki-67 is a prognostic biomarker in lung NENs and, if feasible, proceed to a meta-analysis.

Research, design and methods: Medline (Ovid), Embase, Scopus and the Cochrane library were searched for studies published prior to 28 February 2019 and investigating the role of Ki-67 in lung NENs. Eligible studies were those that included more than 20 patients and provided details of survival outcomes, namely, HRs with CIs according to Ki-67 percentage. Studies not available as a full text or without an English manuscript were excluded. This study was prospectively registered with PROSPERO.

Results: of 11 814 records identified, seven studies met the inclusion criteria. These retrospective studies provided data for 1268 patients (693 TC, 281 AC, 94 large cell neuroendocrine carcinomas and 190 small cell lung carcinomas) and a meta-analysis was carried out to estimate a pooled effect. Random effects analyses demonstrated an association between a high Ki-67 index and poorer overall survival (HR of 2.02, 95% CI 1.16 to 3.52) and recurrence-free survival (HR 1.42; 95% CI 1.01 to 2.00).

Conclusion: this meta-analysis provides evidence that high Ki-67 labelling indices are associated with poor clinical outcomes for patients diagnosed with pulmonary NENs. This study is subject to inherent limitations, but it does provide valuable insights regarding the use of the biomarker Ki-67, in a rare tumour.

Prospero registration number: CRD42018093389.

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Accepted/In Press date: 8 October 2021
Published date: 3 March 2022
Keywords: endocrine tumours, pathology, respiratory tract tumours

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Local EPrints ID: 456479
URI: http://eprints.soton.ac.uk/id/eprint/456479
ISSN: 2044-6055
PURE UUID: e7ccb4ea-f049-437f-9d03-506473b8fb9b

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Date deposited: 03 May 2022 16:51
Last modified: 03 May 2022 16:52

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Contributors

Author: Salma Naheed
Author: Chloe Holden
Author: Lulu Tanno
Author: Linda Pattini
Author: Neil W Pearce
Author: Bryan Green
Author: Eleanor Jaynes
Author: Judith Cave
Author: Giuseppe Pelosi

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