Skip to main content
Erschienen in: Clinical and Translational Oncology 5/2017

15.11.2016 | Research Article

Evaluation of diagnostic and prognostic significance of Ki-67 index in pulmonary carcinoid tumours

verfasst von: V. Clay, G. Papaxoinis, B. Sanderson, J. W. Valle, M. Howell, A. Lamarca, P. Krysiak, P. Bishop, D. Nonaka, W. Mansoor

Erschienen in: Clinical and Translational Oncology | Ausgabe 5/2017

Einloggen, um Zugang zu erhalten

Abstract

Background

Pulmonary carcinoid (PC) tumours are classified as either typical (TC) or atypical (AC) according to mitotic index (MI) and presence of necrosis. The aim of this study was to analyse the diagnostic and prognostic values of the Ki-67 index in PC.

Methods/patients

Between January 2001 and March 2015, we evaluated 94 consecutive patients with a confirmed diagnosis of TC (n = 75) or AC (n = 19) at our institution. Diagnostic histology was centrally reviewed by a local expert neuroendocrine pathologist, with assessment of Ki-67, MI, and necrosis.

Results

Median patient follow-up was 35 months. Eighty-four patients who underwent curative surgical resection were included in the survival analysis for identification of prognostic factors. Ki-67 index showed high diagnostic accuracy to predict histological subtype when assessed by receiver operator characteristic curves with an area under the curve of 0.923 (95% CI 0.852–0.995, p < 0.001). Multivariate analysis showed that MI, Ki-67 index, and the presence or absence of necrosis were independent prognostic factors for relapse-free survival. Combination of MI, Ki-67, and necrosis led to the classification of patients into four different prognostic groups (very low, low, intermediate, and high risks of relapse).

Conclusions

The current study proposes the incorporation of Ki-67 index in the prognostic classification of PC tumours. Due to the limited number of patients and length of follow-up, the current model needs validation by larger cohort studies. Nevertheless, our results suggest that Ki-67 index and MI have continuous effect on prognosis. Prognostic models incorporating multiple cutoffs of Ki-67 and MI might better predict outcome and inform clinical decisions.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Travis WD. Lung tumours with neuroendocrine differentiation. Eur J Cancer. 2009;45(Suppl 1):251–66.CrossRefPubMed Travis WD. Lung tumours with neuroendocrine differentiation. Eur J Cancer. 2009;45(Suppl 1):251–66.CrossRefPubMed
2.
Zurück zum Zitat Rekhtman N. Neuroendocrine tumours of the lung: an update. Arch Pathol Lab Med. 2010;134:1628–38.PubMed Rekhtman N. Neuroendocrine tumours of the lung: an update. Arch Pathol Lab Med. 2010;134:1628–38.PubMed
3.
Zurück zum Zitat Chen LC, Travis WD, Krug LM. Pulmonary neuroendocrine tumours: what (little) do we know? J Natl Compr Canc Netw. 2006;4:623–30.PubMed Chen LC, Travis WD, Krug LM. Pulmonary neuroendocrine tumours: what (little) do we know? J Natl Compr Canc Netw. 2006;4:623–30.PubMed
4.
Zurück zum Zitat Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC. World Health Organisation Classification of Tumours. Pathol Genet Tumours Lung Pleura Thymus Heart, 4th edn. Geneva: WHO; 2004. Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC. World Health Organisation Classification of Tumours. Pathol Genet Tumours Lung Pleura Thymus Heart, 4th edn. Geneva: WHO; 2004.
5.
Zurück zum Zitat Caplin ME, Baudin E, Ferolla P, Filosso P, Garcia-Yuste M, Lim E, Oberg K, Pelosi G, Perren A, Rossi RE, Travis WD, ENETS consensus conference participants. Pulmonary neuroendocrine (carcinoid) tumours: European Neuroendocrine Tumour Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids. Ann Oncol. 2015;26:1604–20.CrossRefPubMed Caplin ME, Baudin E, Ferolla P, Filosso P, Garcia-Yuste M, Lim E, Oberg K, Pelosi G, Perren A, Rossi RE, Travis WD, ENETS consensus conference participants. Pulmonary neuroendocrine (carcinoid) tumours: European Neuroendocrine Tumour Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids. Ann Oncol. 2015;26:1604–20.CrossRefPubMed
6.
Zurück zum Zitat Fink G, Krelbaum T, Yellin A, Bendayan D, Saute M, Glazer M, Kramer MR. Pulmonary carcinoid: Presentation, diagnosis, and outcome in 142 cases in Israel and review of 640 cases from the literature. Chest. 2001;119:1647–51.CrossRefPubMed Fink G, Krelbaum T, Yellin A, Bendayan D, Saute M, Glazer M, Kramer MR. Pulmonary carcinoid: Presentation, diagnosis, and outcome in 142 cases in Israel and review of 640 cases from the literature. Chest. 2001;119:1647–51.CrossRefPubMed
7.
Zurück zum Zitat Travis WD. Advances in neuroendocrine lung tumours. Ann Oncol. 2010;21(Suppl 7):vii65–vii71. Travis WD. Advances in neuroendocrine lung tumours. Ann Oncol. 2010;21(Suppl 7):vii65–vii71.
8.
Zurück zum Zitat Travis WD. The concept of pulmonary neuroendocrine tumours. In: Travis WD, Brambilla E, Müller-Hermelink HK et al., editors. World Health Organisation Classification of Tumours. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. 4th edn. Geneva: WHO; 2004. p. 19–20. Travis WD. The concept of pulmonary neuroendocrine tumours. In: Travis WD, Brambilla E, Müller-Hermelink HK et al., editors. World Health Organisation Classification of Tumours. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. 4th edn. Geneva: WHO; 2004. p. 19–20.
9.
Zurück zum Zitat Warth A, Fink L, Fisseler-Eckhoff A, et al. Interobserver agreement of proliferation index (Ki-67) outperforms mitotic count in pulmonary carcinoids. Virchows Arch. 2013;462:507–13.CrossRefPubMed Warth A, Fink L, Fisseler-Eckhoff A, et al. Interobserver agreement of proliferation index (Ki-67) outperforms mitotic count in pulmonary carcinoids. Virchows Arch. 2013;462:507–13.CrossRefPubMed
10.
Zurück zum Zitat Travis WD, Rush W, Flieder DB, Falk R, Fleming MV, Gal AA, Koss MN. Survival analysis of 200 pulmonary neuroendocrine tumours with clarification of criteria for atypical carcinoid and its separation from typical carcinoid. Am J Surg Pathol. 1998;22:934–44.CrossRefPubMed Travis WD, Rush W, Flieder DB, Falk R, Fleming MV, Gal AA, Koss MN. Survival analysis of 200 pulmonary neuroendocrine tumours with clarification of criteria for atypical carcinoid and its separation from typical carcinoid. Am J Surg Pathol. 1998;22:934–44.CrossRefPubMed
11.
Zurück zum Zitat Skov BG, Holm B, Erreboe A, Skov T, Mellemgaard A. ERCC1 and Ki67 in small cell lung carcinoma and other neuroendocrine tumours of the lung: distribution and impact on survival. J Thorac Oncol. 2010;5:453–9.CrossRefPubMed Skov BG, Holm B, Erreboe A, Skov T, Mellemgaard A. ERCC1 and Ki67 in small cell lung carcinoma and other neuroendocrine tumours of the lung: distribution and impact on survival. J Thorac Oncol. 2010;5:453–9.CrossRefPubMed
12.
Zurück zum Zitat Rindi G, Klöppel G, Alhman H, et al. TNM staging of foregut (neuro)endocrine tumours: a consensus proposal including a grading system. Virchows Arch. 2006;449:395–401.CrossRefPubMedPubMedCentral Rindi G, Klöppel G, Alhman H, et al. TNM staging of foregut (neuro)endocrine tumours: a consensus proposal including a grading system. Virchows Arch. 2006;449:395–401.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Rindi G, Falconi M, Klersy C, et al. TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study. J Natl Cancer Inst. 2012;104:764–77.CrossRefPubMed Rindi G, Falconi M, Klersy C, et al. TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study. J Natl Cancer Inst. 2012;104:764–77.CrossRefPubMed
14.
Zurück zum Zitat Granberg D, Wilander E, Oberg K, Skogseid B. Prognostic markers in patients with typical bronchial carcinoid tumours. J Clin Endocrinol Metab. 2000;85:3425–30.PubMed Granberg D, Wilander E, Oberg K, Skogseid B. Prognostic markers in patients with typical bronchial carcinoid tumours. J Clin Endocrinol Metab. 2000;85:3425–30.PubMed
15.
Zurück zum Zitat Rugge M, Fassan M, Clemente R, Rizzardi G, Giacomelli L, Pennelli G, Mescoli C, Segat D, Rea F. Bronchopulmonary carcinoid: phenotype and long-term outcome in a single-institution series of Italian patients. Clin Cancer Res. 2008;14:149–54.CrossRefPubMed Rugge M, Fassan M, Clemente R, Rizzardi G, Giacomelli L, Pennelli G, Mescoli C, Segat D, Rea F. Bronchopulmonary carcinoid: phenotype and long-term outcome in a single-institution series of Italian patients. Clin Cancer Res. 2008;14:149–54.CrossRefPubMed
16.
Zurück zum Zitat Santinelli A, Ranaldi R, Baccarini M, Mannello B, Bearzi I. Ploidy, proliferative activity, p53 and bcl-2 expression in bronchopulmonary carcinoids: relationship with prognosis. Pathol Res Pract. 1999;195:467–74.CrossRefPubMed Santinelli A, Ranaldi R, Baccarini M, Mannello B, Bearzi I. Ploidy, proliferative activity, p53 and bcl-2 expression in bronchopulmonary carcinoids: relationship with prognosis. Pathol Res Pract. 1999;195:467–74.CrossRefPubMed
17.
Zurück zum Zitat Costes V, Marty-Ané C, Picot MC, Serre I, Pujol JL, Mary H, Baldet P. Typical and atypical bronchopulmonary carcinoid tumours: a clinicopathologic and KI-67-labeling study. Hum Pathol. 1995;26:740–5.CrossRefPubMed Costes V, Marty-Ané C, Picot MC, Serre I, Pujol JL, Mary H, Baldet P. Typical and atypical bronchopulmonary carcinoid tumours: a clinicopathologic and KI-67-labeling study. Hum Pathol. 1995;26:740–5.CrossRefPubMed
18.
Zurück zum Zitat Grimaldi F, Muser D, Beltrami C, et al. Partitioning of bronchopulmonary carcinoids in two different prognostic categories by Ki-67 score. Front Endocrinol (Lausanne). 2011;2:20. Grimaldi F, Muser D, Beltrami C, et al. Partitioning of bronchopulmonary carcinoids in two different prognostic categories by Ki-67 score. Front Endocrinol (Lausanne). 2011;2:20.
19.
Zurück zum Zitat Swarts DR, van Suylen RJ, den Bakker MA, et al. Interobserver variability for the WHO classification of pulmonary carcinoids. Am J Surg Pathol. 2014;38:1429–36.CrossRefPubMed Swarts DR, van Suylen RJ, den Bakker MA, et al. Interobserver variability for the WHO classification of pulmonary carcinoids. Am J Surg Pathol. 2014;38:1429–36.CrossRefPubMed
20.
Zurück zum Zitat Zahel T, Krysa S, Herpel E, Stenzinger A, Goeppert B, Schirmacher P, Hoffmann H, Schnabel PA, Warth A. Phenotyping of pulmonary carcinoids and a Ki-67-based grading approach. Virchows Arch. 2012;460:299–308.CrossRefPubMed Zahel T, Krysa S, Herpel E, Stenzinger A, Goeppert B, Schirmacher P, Hoffmann H, Schnabel PA, Warth A. Phenotyping of pulmonary carcinoids and a Ki-67-based grading approach. Virchows Arch. 2012;460:299–308.CrossRefPubMed
21.
Zurück zum Zitat Walts AE, Ines D, Marchevsky AM. Limited role of Ki-67 proliferative index in predicting overall short-term survival in patients with typical and atypical pulmonary carcinoid tumours. Mod Pathol. 2012;25:1258–64.CrossRefPubMed Walts AE, Ines D, Marchevsky AM. Limited role of Ki-67 proliferative index in predicting overall short-term survival in patients with typical and atypical pulmonary carcinoid tumours. Mod Pathol. 2012;25:1258–64.CrossRefPubMed
22.
Zurück zum Zitat Rindi G, Klersy C, Inzani F, et al. Grading the neuroendocrine tumours of the lung: an evidence-based proposal. Endocr Relat Cancer. 2013;21:1–16.CrossRefPubMed Rindi G, Klersy C, Inzani F, et al. Grading the neuroendocrine tumours of the lung: an evidence-based proposal. Endocr Relat Cancer. 2013;21:1–16.CrossRefPubMed
23.
Zurück zum Zitat Rekhtman N. Neuroendocrine tumours of the lung: an update. Arch Pathol Lab Med. 2010;134:1628–38.PubMed Rekhtman N. Neuroendocrine tumours of the lung: an update. Arch Pathol Lab Med. 2010;134:1628–38.PubMed
24.
Zurück zum Zitat Pelosi G, Rindi G, Travis WD, Papotti M. Ki-67 antigen in lung neuroendocrine tumours: unraveling a role in clinical practice. J Thorac Oncol. 2014;9:273–84.CrossRefPubMed Pelosi G, Rindi G, Travis WD, Papotti M. Ki-67 antigen in lung neuroendocrine tumours: unraveling a role in clinical practice. J Thorac Oncol. 2014;9:273–84.CrossRefPubMed
Metadaten
Titel
Evaluation of diagnostic and prognostic significance of Ki-67 index in pulmonary carcinoid tumours
verfasst von
V. Clay
G. Papaxoinis
B. Sanderson
J. W. Valle
M. Howell
A. Lamarca
P. Krysiak
P. Bishop
D. Nonaka
W. Mansoor
Publikationsdatum
15.11.2016
Verlag
Springer International Publishing
Erschienen in
Clinical and Translational Oncology / Ausgabe 5/2017
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-016-1568-z

Weitere Artikel der Ausgabe 5/2017

Clinical and Translational Oncology 5/2017 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.