Skip to main content

Advertisement

SpringerLink
Log in

Malignancies associated with GIST: a retrospective study with molecular analysis of KIT and PDGFRA

  • Original Article
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Purpose

Gastrointestinal stromal tumors (GISTs) are the most common soft tissue tumors of the GI tract. Studies have been published reporting additional neoplasms in GIST patients. This study aimed to evaluate possible associations of mutation type, morphology, and clinical aspects of GISTs.

Methods

All cases of GIST were identified from our pathology files. Coding exons of KIT and PDGFRA in GISTs with additional malignancies were sequenced.

Results

A total of 70 of 188 (37%) retrieved patients with confirmed diagnosis of GIST showed at least one additional malignant neoplasm. Fifty of these GISTs were located in the stomach (71%), 8 in the small intestine (11%), 5 in the colon/rectum (7%), and 7 cases (6.2%) were of undetermined sites of origin. The distribution of identified mutations was similar to that described in GISTs without secondary malignancies. A total of 37 of 57 cases (65%) showed mutations in the KIT gene exon 11, 3 (5%) cases in exon 9, and 1 (2%) case in exon 13. Nine tumors (16%) had mutations of the PDGFRA gene. KIT and PDGFRA wild-type status were found in seven cases (12%). Most of the secondary neoplasms were located within the GI tract (34%), in the urogenital system (24%), or the breast/female genital tract (20%).

Conclusion

This study confirms the high rate of additional malignant tumors in GIST patients. GIST features in these cases are very similar to those with sole GIST.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Agaimy A, Wünsch PH, Sobin LH, Lasota J, Miettinen M (2006) Occurrence of other malignancies in patients with gastrointestinal stromal tumors. Semin Diagn Pathol 23:120–129

    Article  PubMed  Google Scholar 

  2. Aghdassi A, Christoph A, Dombrowski F, Döring P, Barth C, Christoph J, Lerch MM, Simon P (2018) Gastrointestinal stromal tumors: clinical symptoms, location, metastasis formation, and associated malignancies in a single center retrospective study. Dig Dis 36:337–345

    Article  PubMed  Google Scholar 

  3. Amankwah EK, Conley AP, Reed DR (2013) Epidemiology and therapies for metastatic sarcoma. Clin Epidemiol 5:147–162

    PubMed  PubMed Central  Google Scholar 

  4. Corless CL, Barnett CM, Heinrich MC (2011) Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer 11:865–878

    Article  CAS  PubMed  Google Scholar 

  5. Dumont AG, Rink L, Godwin AK, Miettinen M, Joensuu H, Strosberg JR, Gronchi A, Corless CL, Goldstein D, Rubin BP, Maki RG, Lazar AJ, Lev D, Trent JC, von Mehren M (2012) A nonrandom association of gastrointestinal stromal tumor (GIST) and desmoid tumor (deep fibromatosis): case series of 28 patients. Ann Oncol 23:1335–1340

    Article  CAS  PubMed  Google Scholar 

  6. Fernández JA, Olivares V, Gómez-Ruiz AJ et al (2018) Additional malignancies in patients with gastrointestinal stromal tumors (GIST): incidence, pathology and prognosis according to a time of occurrence-based classification. Clin Transl Oncol. https://doi.org/10.1007/s12094-018-1966-5

  7. Goncalves R, Linhares E, Albagli R et al (2010) Occurrence of other tumors in patients with GIST. Surg Oncol 19:e140–e143

    Article  PubMed  Google Scholar 

  8. Hechtman JF, Dematteo R, Nafa K et al (2015) Additional primary malignancies in patients with gastrointestinal stromal tumor (GIST): a clinicopathologic study of 260 patients with molecular analysis and review of the literature. Ann Surg Oncol 22:2633–2639

    Article  PubMed  PubMed Central  Google Scholar 

  9. Hirota S, Isozaki K, Moriyama Y et al (1998) Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 279:577–580

    Article  CAS  PubMed  Google Scholar 

  10. Joensuu H, Eriksson M, Hall KS, Hartmann JT, Pink D, Schütte J, Ramadori G, Hohenberger P, Duyster J, al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Sarlomo-Rikala M, Nilsson B, Sihto H, Ballman KV, Leinonen M, DeMatteo RP, Reichardt P (2014) Risk factors for gastrointestinal stromal tumor recurrence in patients treated with adjuvant imatinib. Cancer 120:2325–2333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kramer K, Wolf S, Mayer B, Schmidt SA, Agaimy A, Henne-Bruns D, Knippschild U, Schwab M, Schmieder M (2015) Frequence, spectrum and prognostic impact of additional malignancies in patients with gastrointestinal stromal tumors. Neoplasia 17:134–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mendonca SJ, Sanchez A, Blum KA, Ghanaat M, Kashan MY, Benfante N, Russo P, Coleman JA, Crago AM, Hakimi AA (2018) The association of renal cell carcinoma with gastrointestinal stromal tumors. J Surg Oncol 117:1716–1720

    Article  PubMed  PubMed Central  Google Scholar 

  13. Miettinen M, Lasota J (2006) Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med 130:1466–1478

    CAS  PubMed  Google Scholar 

  14. Miettinen M, Sobin LH, Lasota J (2005) Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol 29:52–68

    Article  PubMed  Google Scholar 

  15. Miranda C, Nucifora M, Molinari F, Conca E, Anania MC, Bordoni A, Saletti P, Mazzucchelli L, Pilotti S, Pierotti MA, Tamborini E, Greco A, Frattini M (2012) KRAS and BRAF mutations predict primary resistance to imatinib in gastrointestinal stromal tumors. Clin Cancer Res 18:1769–1776

    Article  CAS  PubMed  Google Scholar 

  16. Murphy JD, Ma GL, Baumgartner JM, Madlensky L, Burgoyne AM, Tang CM, Martinez ME, Sicklick JK (2015) Increased risk of additional cancers among patients with gastrointestinal stromal tumors: a population-based study. Cancer 121:2960–2967

    Article  PubMed  PubMed Central  Google Scholar 

  17. Nilsson B, Bumming P, Meis-Kindblom JM et al (2005) Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era—a population-based study in western Sweden. Cancer 103:821–829

    Article  PubMed  Google Scholar 

  18. Pandurengan RK, Dumont AG, Araujo DM, Ludwig JA, Ravi V, Patel S, Garber J, Benjamin RS, Strom SS, Trent JC (2010) Survival of patients with multiple primary malignancies: a study of 783 patients with gastrointestinal stromal tumor. Ann Oncol 21:2107–2111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Rodriquenz MG, Rossi S, Ricci R, Martini M, Larocca M, Dipasquale A, Quirino M, Schinzari G, Basso M, D’Argento E, Strippoli A, Barone C, Cassano A (2016) Gastrointestinal stromal tumors (GISTs) and second malignancies: a novel “sentinel tumor”? A monoinstitutional, STROBE-compliant observational analysis. Medicine (Baltimore) 95:e4718

    Article  Google Scholar 

  20. Rubio-Casadevall J, Borras JL, Carmona-Garcia MC et al (2015) Correlation between mutational status and survival and second cancer risk assessment in patients with gastrointestinal stromal tumors: a population-based study. World J Surg Oncol 13:47

    Article  PubMed  PubMed Central  Google Scholar 

  21. Smith MJ, Smith HG, Mahar AL, Law C, Ko YJ (2016) The impact of additional malignancies in patients diagnosed with gastrointestinal stromal tumors. Int J Cancer 139:1744–1751

    Article  CAS  PubMed  Google Scholar 

  22. Tran T, Davila JA, El-Serag HB (2005) The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992 to 2000. Am J Gastroenterol 100:162–168

    Article  PubMed  Google Scholar 

  23. Vassos N, Agaimy A, Hohenberger W, Croner RS (2014) Coexistence of gastrointestinal stromal tumours (GIST) and malignant neoplasms of different origin: prognostic implications. Int J Surg 12:371–377

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Mrs. Monika Müller and Mr. Kai Hebick, both at clinical center Augsburg, for the acquisition of paraffin-embedded tissue and data management as well as Mrs. Ingrid Mons, Department of Pathology of the University of Erlangen, for the support in molecular analysis.

Funding

This study was financially supported by Novartis AG. There was no influence on the study design, aim, or data analysis.

Author information

Author notes

  1. Patrick Mayr and Bruno Märkl contributed equally to this work.

Authors and Affiliations

  1. Institute of Pathology, Klinikum Augsburg, Augsburg, Germany

    Patrick Mayr, Bruno Märkl & Sebastian Dintner

  2. Department of Radiooncology, Klinikum Augsburg, Augsburg, Germany

    Patrick Mayr

  3. Department of Pathology, FAU Erlangen-Nürnberg, Erlangen, Germany

    Abbas Agaimy & Regine Schneider-Stock

  4. Department of Visceral Surgery, Klinikum Augsburg, Augsburg, Germany

    Bernadette Kriening

  5. Clinical and Population-Based Cancer Registry of Augsburg, Klinikum Augsburg, Augsburg, Germany

    Gerhard Schenkirsch

  6. Experimental Tumor pathology, Department of Pathology, FAU Erlangen-Nürnberg, Erlangen, Germany

    Regine Schneider-Stock

Authors
  1. Patrick Mayr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bruno Märkl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abbas Agaimy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bernadette Kriening
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sebastian Dintner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gerhard Schenkirsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Regine Schneider-Stock
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Patrick Mayr: study design, data acquisition and interpretation, manuscript drafting. Bruno Märkl: manuscript drafting and study design.Abbas Agaimy: manuscript drafting and data interpretation. Bernadette Kriening: data acquisition. Sebastian Dintner: data analysis and data acquisition. Gerhard Schenkirsch: data acquisition. Regine Schneider-Stock: study design, data acquisition and interpretation, and manuscript drafting.

Corresponding author

Correspondence to Bruno Märkl.

Ethics declarations

This study was approved by the ethical board of Klinikum Augsburg.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mayr, P., Märkl, B., Agaimy, A. et al. Malignancies associated with GIST: a retrospective study with molecular analysis of KIT and PDGFRA. Langenbecks Arch Surg 404, 605–613 (2019). https://doi.org/10.1007/s00423-019-01773-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00423-019-01773-2

Keywords

Search

Navigation