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KI-67 heterogeneity in well differentiated gastro-entero-pancreatic neuroendocrine tumors: when is biopsy reliable for grade assessment?

An Erratum to this article was published on 19 August 2017

This article has been updated

Abstract

Purpose

Ki-67 heterogeneity can impact on gastroenteropancreatic neuroendocrine tumor grade assignment, especially when tissue is scarce. This work is aimed at devising adequacy criteria for grade assessment in biopsy specimens.

Method

To analyze the impact of biopsy size on reliability, 360 virtual biopsies of different thickness and lengths were constructed. Furthermore, to estimate the mean amount of non-neoplastic tissue component present in biopsies, 28 real biopsies were collected, the non-neoplastic components (fibrosis and inflammation) quantified and the effective area of neoplastic tissue calculated for each biopsy.

Results

Heterogeneity of Ki-67 distribution, G2 tumors and biopsy size all play an important role in reducing the reliability of biopsy samples in Ki-67-based grade assignment. In particular in G2 cases, 59.9% of virtual biopsies downgraded the tumor and the smaller the biopsy, the more frequent downgrading occurs. In real biopsies the presence of non-neoplastic tissue reduced the available total area by a mean of 20%.

Conclusions

By coupling the results from these two different approaches we show that both biopsy size and non-neoplastic component must be taken into account for biopsy adequacy. In particular, we can speculate that if the minimum biopsy area, necessary to confidently (80% concordance) grade gastro-entero-pancreatic neuroendocrine tumors on virtual biopsies ranges between 15 and 30 mm2, and if real biopsies are on average composed of only 80% of neoplastic tissue, then biopsies with a surface area not <12 mm2 should be performed; using 18G needles, this corresponds to a minimum total length of 15 mm.

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Change history

  • 19 August 2017

    An erratum to this article has been published.

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Acknowledgements

We thank Miss Simona Pigozzi for technical support in immunohistochemistry.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector

Author contributions

Dr. Grillo devised the work, performed the Ki-67 counting and wrote the manuscript. Dr. Valle performed the Ki-67 counting and wrote the manuscript. Prof. Ferone, Dr. Albertelli, and Dr. Cittadini aided in devising the study. Dr. Brisigotti collected samples and performed Ki-67 counting. Prof. Fiocca and Dr. Vanoli critically reviewed the work and manuscript. Dr. Mastracci wrote and critically reviewed the work.

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Correspondence to Federica Grillo.

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The authors declare that they have no competing interests.

Additional information

The original version of this article was revised: the first and surname of all the authors are corrected.

Federica Grillo and Luca Valle contributed equally to this work.

An erratum to this article is available at https://doi.org/10.1007/s12020-017-1389-z.

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Grillo, F., Valle, L., Ferone, D. et al. KI-67 heterogeneity in well differentiated gastro-entero-pancreatic neuroendocrine tumors: when is biopsy reliable for grade assessment?. Endocrine 57, 494–502 (2017). https://doi.org/10.1007/s12020-017-1364-8

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  • DOI: https://doi.org/10.1007/s12020-017-1364-8

Keywords

  • Gastroenteropancreatic neuroendocrine tumors
  • Grade
  • Ki-67
  • Biopsy