Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jul 28;18(1):51.
doi: 10.1186/s12902-018-0274-y.

Variability of the Ki-67 proliferation index in gastroenteropancreatic neuroendocrine neoplasms - a single-center retrospective study

Huiying Shi  1 , Qin Zhang  2 , Chaoqun Han  1 , Ding Zhen  1 , Rong Lin  3
Affiliations

Variability of the Ki-67 proliferation index in gastroenteropancreatic neuroendocrine neoplasms - a single-center retrospective study

Huiying Shi et al. BMC Endocr Disord. .

Abstract

Background: The Ki-67 index in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) may change throughout the disease course. However, the definitive effect of Ki-67 variability on GEP-NENs remains unknown. The aims of this study were to evaluate changes in Ki-67 levels throughout the disease course and investigate the role of Ki-67 index variability in GEP-NENs.

Methods: Specimens with multiple pathologies were evaluated from 30 patients who were selected from 514 patients with GEP-NENs, being treated at Wuhan Union Hospital from July 2009 to February 2018. The Ki-67 index was evaluated among multiple specimens over the disease course. Univariable and multivariable Cox proportional hazards regression analyses were performed to assess the prognostic significance of various clinical and histopathologic features.

Results: Among the 514 patients with GEP-NENs, metastases were seen in 182 (35.41%). Among the 30 patients from whom specimens with multiple pathologies were obtained, 24 were both primary and metastatic specimens and six were specimens collected over the course of the disease. Changes in Ki-67 levels were detected in 53.3% of the patients, of whom 40% had up-regulated Ki-67 levels, and 13.3% had down-regulated Ki-67 levels. Kaplan-Meier survival analysis showed that the group with Ki-67 variability had a shorter overall survival (p = 0.0297). The Cox regression analysis indicated that Ki-67 variability (p = 0.038) was the only independent prognostic factor for overall survival.

Conclusions: Our data suggest that patients with GEP-NENs and Ki-67 variability had a poorer prognosis. The re-assessment of Ki-67 at sites of metastasis or during the disease course might play a role in predicting the prognosis of patients with GEP-NENs. This finding could have implications for how GEP-NENs are monitored and treated.

Keywords: Gastroenteropancreatic neuroendocrine neoplasms; Ki-67; Metastases; Prognostic factors; Variability.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the ethics committee of Tongji Medical College, Huazhong University of Science and Technology (IORG No: IORG0003571), and performed in accordance with the Declaration of Helsinki. As it was a retrospective study, all data were collected from a medical records system. Therefore, the study was exempt from the requirement to obtain individual informed consent, based on the Ethical Guidelines of the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Distribution of variable cases according to GEP-NENs grade (a) and primary tumor site (b)
Fig. 2
Fig. 2
Survival curves in patients with GEP-NENs according to (a) Ki-67 index variability, (b) Sex, (c) Primary tumor site, (d) Metastatic tumor site
See this image and copyright information in PMC

References

    1. Miller HC, Drymousis P, Flora R, Goldin R, Spalding D, Frilling A. Role of Ki-67 proliferation index in the assessment of patients with neuroendocrine neoplasias regarding the stage of disease. World J Surg. 2014;38(6):1353–1361. doi: 10.1007/s00268-014-2451-0. - DOI - PubMed
    1. Singh S, Hallet J, Rowsell C, Law CH. Variability of Ki67 labeling index in multiple neuroendocrine tumors specimens over the course of the disease. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2014;40(11):1517–1522. doi: 10.1016/j.ejso.2014.06.016. - DOI - PubMed
    1. Foltyn W, Zajecki W, Marek B, Kajdaniuk D, Sieminska L, Zemczak A, Kos-Kudla B. The value of the Ki-67 proliferation marker as a prognostic factor in gastroenteropancreatic neuroendocrine tumours. Endokrynologia Polska. 2012;63(5):362–366. - PubMed
    1. Kleihues PSL. Lyon: IARC press. 2004. World Health Organization classification of Tumours. Pathology and genetics of endocrine organs.
    1. Bosman FT CF, Hruban RH et al: WHO Classification of Tumours of the Digestive System, 4th edition. Geneva, Switzerland: WHO Press 2010, ISBN978–92–832–2432–7.

MeSH terms

Supplementary concepts