Top

European Journal of Nuclear Medicine and Molecular Imaging

Published in:

Open Access 08-06-2022 | Carcinoid Tumor | Original Article

Correlation of somatostatin receptor PET/CT imaging features and immunohistochemistry in neuroendocrine tumors of the lung: a retrospective observational study

Authors: Vittoria Rufini, Margherita Lorusso, Frediano Inzani, Tina Pasciuto, Elizabeth Katherine Anna Triumbari, Lucia Rosalba Grillo, Filippo Locco, Stefano Margaritora, Edoardo Pescarmona, Guido Rindi

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 12/2022

Abstract

Purpose

To correlate somatostatin receptor (SSTR) and proliferative activity profile (SSTR2, SSTR5, Ki-67) at immunohistochemistry (IHC) with SSTR-PET/CT imaging features in a retrospective series of lung neuroendocrine tumors (NET). Proliferative activity by Ki-67 and ¹⁸F-FDG-PET/CT parameters (when available) were also correlated.

Methods

Among 551 patients who underwent SSTR-PET/CT with ⁶⁸Ga-DOTA-somatostatin analogs (SSA) between July 2011 and March 2020 for lung neuroendocrine neoplasms, 32 patients with a confirmed diagnosis of NET were included. For 14 of them, ¹⁸F-FDG-PET/CT was available. PET/CT images were reviewed by qualitative and semi-quantitative analyses. Immunohistochemistry for SSTR2, SSTR5, and Ki-67 was assessed. Inferential analysis was performed including kappa statistics and Spearman’s rank correlation test.

Results

Definitive diagnosis consisted of 26 typical carcinoids-G1 and six atypical carcinoids-G2. Positive SSTR2-IHC was found in 62.5% of samples while SSTR5-IHC positivity was 19.4%. A correlation between SSTR2-IHC and SSTR-PET/CT was found in 24/32 cases (75.0%, p = 0.003): 20 were concordantly positive, 4 concordantly negative. For positive IHC, 100% concordance with SSTR-PET/CT (both positive) was observed, while for negative IHC concordance (both negative) was 33.3%. In 8 cases, IHC was negative while SSTR-PET/CT was positive, even though with low-grade uptake in all but one. A significant correlation between SUV_max values at SSTR-PET/CT and the SSTR2-IHC scores was found, with low SUV_max values corresponding to negative IHC and higher SUV_max values to positive IHC (p = 0.002).

Conclusion

This retrospective study showed an overall good agreement between SSTR2-IHC and tumor uptake at SSTR-PET/CT in lung NETs. SSTR-PET/CT SUV_max values can be used as a parameter of SSTR2 density. Within the limits imposed by the relatively small cohort, our data suggest that SSTR2-IHC may surrogate SSTR-PET/CT in selected lung NET patients for clinical decision making when SSTR-PET/CT is not available.

Fink G, Krelbaum T, Yellin A, Bendayan D, Saute M, Glazer M, et al. Pulmonary carcinoid: presentation, diagnosis, and outcome in 142 cases in Israel and review of 640 cases from the literature. Chest. 2001;119:1647–51. https://doi.org/10.1378/chest.119.6.1647.CrossRefPubMed

Rindi G, Klimstra DS, Abedi-Ardekani B, Asa SL, Bosman FT, Brambilla E, et al. A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Mod Pathol. 2018;31:1770–86. https://doi.org/10.1038/s41379-018-0110-y.CrossRefPubMedPubMedCentral

Travis WD, Beasley MB, Cree IA et al. Chapter 1.4.1: Lung neuroendocrine neoplasms: Introduction. In: WHO Classification of Tumours Editorial Board. Thoracic tumours. Lyon (France): International Agency for Research on Cancer; 2021. (WHO classification of tumours series, 5th ed.; vol. 5, pp. 127–129). https://publications.iarc.fr/595.

Papotti M, Brambilla E, Dingemans AC et al. Chapter 1.4.3.1: Carcinoid/Neuroendocrine tumour of the lung. In: WHO Classification of Tumours Editorial Board. Thoracic tumours. Lyon (France): International Agency for Research on Cancer; 2021. (WHO classification of tumours series, 5th ed.; vol.5, pp. 133–8). https://publications.iarc.fr/595.

Papotti M, Croce S, Bellò M, Bongiovanni M, Allìa E, Schindler M, et al. Expression of somatostatin receptor types 2, 3 and 5 in biopsies and surgical specimens of human lung tumours. Correlation with preoperative octreotide scintigraphy. Virchows Arch. 2001;439:787–97. https://doi.org/10.1007/s004280100494.CrossRefPubMed

Smit Duijzentkunst DA, Kwekkeboom DJ, Bodei L. Somatostatin receptor 2-targeting compounds. J Nucl Med. 2017;58(Suppl 2):54S-60S. https://doi.org/10.2967/jnumed.117.191015.CrossRefPubMed

Ambrosini V, Kunikowska J, Baudin E, Bodei L, Bouvier C, Capdevila J, et al. Consensus on molecular imaging and theranostics in neuroendocrine neoplasms. Eur J Cancer. 2021;146:56–73. https://doi.org/10.1016/j.ejca.2021.01.008.CrossRefPubMedPubMedCentral

Singh S, Bergsland EK, Card CM, Hope TA, Kunz PL, Laidley DT, et al. Commonwealth neuroendocrine tumour research collaboration and the North American neuroendocrine tumor society guidelines for the diagnosis and management of patients with lung neuroendocrine tumors: an international collaborative endorsement and update of the 2015 European Neuroendocrine Tumor Society Expert Consensus Guidelines. J Thorac Oncol. 2020;15:1577–98. https://doi.org/10.1016/j.tho.2020.06.021.CrossRefPubMed

Jiang Y, Hou G, Cheng W. The utility of ¹⁸F-FDG and ⁶⁸Ga-DOTA-Peptide PET/CT in the evaluation of primary pulmonary carcinoid: a systematic review and meta-analysis. Medicine (Baltimore). 2019;98:e14769. https://doi.org/10.1097/MD.0000000000014769.CrossRef

10.

Martucci F, Pascale M, Valli MC, Pesce GA, Froesch P, Giovanella L, et al. Impact of ¹⁸F-FDG PET/CT in staging patients with small cell lung cancer: a systematic review and meta-analysis. Front Med (Lausanne). 2020;6:336. https://doi.org/10.3389/fmed.2019.00336.CrossRef

11.

Kaira K, Murakami H, Endo M, Ohde Y, Naito T, Kondo H, et al. Biological correlation of ¹⁸F-FDG uptake on PET in pulmonary neuroendocrine tumors. Anticancer Res. 2013;33:4219–28.PubMed

12.

Lococo F, Cesario A, Paci M, Filice A, Versari A, Rapicetta C, et al. PET/CT assessment of neuroendocrine tumors of the lung with special emphasis on bronchial carcinoids. Tumour Biol. 2014;35:8369–77. https://doi.org/10.1007/s13277-014-2102-y.CrossRefPubMed

13.

Volante M, Brizzi MP, Faggiano A, La Rosa S, Rapa I, Ferrero A, et al. Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy. Mod Pathol. 2007;20:1172–82. https://doi.org/10.1038/modpathol.3800954.CrossRefPubMed

14.

Volante M, Bozzalla-Cassione F, Papotti M. Somatostatin receptors and their interest in diagnostic pathology. Endocr Pathol. 2004;15:275–91. https://doi.org/10.1385/ep:15:4:275.CrossRefPubMed

15.

Miederer M, Seidl S, Buck A, Scheidhauer K, Wester HJ, Schwaiger M, Perren A. Correlation of immunohistopathological expression of somatostatin receptor 2 with standardized uptake values in ⁶⁸Ga-DOTATOC PET/CT. Eur J Nucl Med Mol Imaging. 2009;36:48–52. https://doi.org/10.1007/s00259-008-0944-5.CrossRefPubMed

16.

Treglia G, Castaldi P, Villani MF, Perotti G, de Waure C, Filice A, et al. Comparison of ¹⁸F-DOPA, ¹⁸F-FDG and ⁶⁸Ga-somatostatin analogue PET/CT in patients with recurrent medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2012;39:569–80. https://doi.org/10.1007/s00259-011-2031-6.CrossRefPubMed

17.

European Pharmacopeia 7.7 (01/2013:2482 Gallium (68Ga) Edotreotide injection) Eur Pharm. 2011; 23:310–3.

18.

Hofman MS, Lau WF, Hicks RJ. Somatostatin receptor imaging with ⁶⁸Ga DOTATATE PET/CT: clinical utility, normal patterns, pearls, and pitfalls in interpretation. Radiographics. 2015;35:500–16. https://doi.org/10.1148/rg.352140164.CrossRefPubMed

19.

Quak E, le Roux PY, Hofman MS, Robin P, Bourhis D, Callahan J, et al. Harmonizing FDG PET quantification while maintaining optimal lesion detection: prospective multicentre validation in 517 oncology patients. Eur J Nucl Med Mol Imaging. 2015;42:2072–82. https://doi.org/10.1007/s00259-015-3128-0.CrossRefPubMedPubMedCentral

20.

Lococo F, Perotti G, Cardillo G, Waure De, c, Filice A, Graziano P, et al. Multicenter comparison of ¹⁸F-FDG and ⁶⁸Ga-DOTA-peptide PET/CT for pulmonary carcinoid. Clin Nucl Med. 2015;40:e183-9. https://doi.org/10.1097/RLU.0000000000000641.CrossRefPubMed

21.

Amin MB. AJCC Cancer Staging Manual, VIII ed.; Springer-Verlag: Berlin/Heidelberg, Germany. 2017.

22.

Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159–74. https://doi.org/10.2307/2529310.CrossRefPubMed

23.

Lenotti E, Alberti A, Spada F, Amoroso V, Maisoneuve P, Grisanti S, et al. Outcome of patients with metastatic lung neuroendocrine tumors submitted to first line monotherapy with somatostatin analogs. Front Endocrinol (Lausanne). 2021;12:669484. https://doi.org/10.3389/fendo.2021.669484.CrossRef

24.

Mirvis E, Toumpanakis C, Mandair D, Gnanasegaran G, Caplin M, Navalkissoor S. Efficacy and tolerability of peptide receptor radionuclide therapy (PRRT) in advanced metastatic bronchial neuroendocrine tumours (NETs). Lung Cancer. 2020;150:70–5. https://doi.org/10.1016/j.lungcan.2020.10.005.CrossRefPubMed

25.

Park S, Parihar AS, Bodei L, Hope TA, Mallak N, Millo C, et al. Somatostatin receptor imaging and theranostics: current practice and future prospects. J Nucl Med. 2021;62:1323–9. https://doi.org/10.2967/jnumed.120.251512.CrossRefPubMedPubMedCentral

26.

Sundin A, Arnold R, Baudin E, Cwikla JB, Eriksson B, Fanti S, et al. ENETS Consensus Guidelines for the standards of care in neuroendocrine tumors: radiological, nuclear medicine & hybrid imaging. Neuroendocrinology. 2017;105:212–44. https://doi.org/10.1159/000471879.CrossRefPubMed

27.

Vesterinen T, Leijon H, Mustonen H, Remes S, Knuuttila A, Salmenkivi K, et al. Somatostatin receptor expression is associated with metastasis and patient outcome in pulmonary carcinoid tumors. J Clin Endocrinol Metab. 2019;104:2083–93. https://doi.org/10.1210/jc.2018-01931.CrossRefPubMed

28.

Righi L, Volante M, Tavaglione V, Billè A, Daniele L, Angusti T, et al. Somatostatin receptor tissue distribution in lung neuroendocrine tumours: a clinicopathologic and immunohistochemical study of 218 “clinically aggressive” cases. Ann Oncol. 2010;21:548–55. https://doi.org/10.1093/annonc/mdp334.CrossRefPubMed

29.

Reubi JC, Schär JC, Waser B, Wenger S, Heppeler A, Schmitt JS, et al. Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med. 2000;27:273–82. https://doi.org/10.1007/s002590050034.CrossRefPubMed

30.

Lichtenauer-Kaligis EG, Dalm VA, Oomen SP, Mooij DM, van Hagen PM, Lamberts SW, et al. Differential expression of somatostatin receptor subtypes in human peripheral blood mononuclear cell subsets. Eur J Endocrinol. 2004;150:565–77. https://doi.org/10.1530/eje.0.1500565 (Erratum in Eur J Endocrinol 2005 152:325).CrossRefPubMed

31.

Reubi JC, Mazzucchelli L, Laissue JA. Intestinal vessels express a high density of somatostatin receptors in human inflammatory bowel disease. Gastroenterology. 1994;106:951–9. https://doi.org/10.1016/0016-5085(94)90754-4.CrossRefPubMed

32.

Kaemmerer D, Peter L, Lupp A, Schulz S, Sänger J, Prasad V, et al. Molecular imaging with ⁶⁸Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2011;38:1659–68. https://doi.org/10.1007/s00259-011-1846-5.CrossRefPubMed

33.

Campana D, Ambrosini V, Pezzilli R, Fanti S, Labate AM, Santini D, et al. Standardized uptake values of ⁶⁸Ga-DOTANOC PET: a promising prognostic tool in neuroendocrine tumors. J Nucl Med. 2010;51:353–9. https://doi.org/10.2967/jnumed.109.066662.CrossRefPubMed

Title: Correlation of somatostatin receptor PET/CT imaging features and immunohistochemistry in neuroendocrine tumors of the lung: a retrospective observational study
Authors: Vittoria Rufini
Margherita Lorusso
Frediano Inzani
Tina Pasciuto
Elizabeth Katherine Anna Triumbari
Lucia Rosalba Grillo
Filippo Locco
Stefano Margaritora
Edoardo Pescarmona
Guido Rindi
Publication date: 08-06-2022
Publisher: Springer Berlin Heidelberg
Keywords: Carcinoid Tumor
Neuroendocrine Tumor
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 12/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-022-05848-z

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Correlation of somatostatin receptor PET/CT imaging features and immunohistochemistry in neuroendocrine tumors of the lung: a retrospective observational study

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 12/2022

Direct inference of Patlak parametric images in whole-body PET/CT imaging using convolutional neural networks

The era of prostate-specific membrane antigen (PSMA)–based theranostics for hepatocellular carcinoma is upcoming: are we ready for it?

Correction to: Correlation of somatostatin receptor PET/CT imaging features and immunohistochemistry in neuroendocrine tumors of the lung: a retrospective observational study

In vivo detection of hydrogen sulfide in the brain of live mouse: application in neuroinflammation models

Diagnostic performance of [18F]-FDG PET/MR in evaluating colorectal cancer: a systematic review and meta-analysis

Preclinical evaluation and pilot clinical study of [18F]AlF-NOTA-FAPI-04 for PET imaging of rheumatoid arthritis