Top

Published in:

01-08-2019 | Gastrointestinal Stromal Tumor | Original Article

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

Authors: Patrick Mayr, Bruno Märkl, Abbas Agaimy, Bernadette Kriening, Sebastian Dintner, Gerhard Schenkirsch, Regine Schneider-Stock

Published in: Langenbeck's Archives of Surgery | Issue 5/2019

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.

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

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 36:337–345CrossRefPubMed

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

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

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 23:1335–1340CrossRefPubMed

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

Goncalves R, Linhares E, Albagli R et al (2010) Occurrence of other tumors in patients with GIST. Surg Oncol 19:e140–e143CrossRefPubMed

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 22:2633–2639CrossRefPubMedPubMedCentral

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

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 120:2325–2333CrossRefPubMedPubMedCentral

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 17:134–140CrossRefPubMedPubMedCentral

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 117:1716–1720CrossRefPubMedPubMedCentral

13.

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

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 29:52–68CrossRefPubMed

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 18:1769–1776CrossRefPubMed

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 121:2960–2967CrossRefPubMedPubMedCentral

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 103:821–829CrossRefPubMed

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 21:2107–2111CrossRefPubMedPubMedCentral

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:e4718CrossRef

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 13:47CrossRefPubMedPubMedCentral

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 139:1744–1751CrossRefPubMed

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 100:162–168CrossRefPubMed

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 12:371–377CrossRefPubMed

Title: Malignancies associated with GIST: a retrospective study with molecular analysis of KIT and PDGFRA
Authors: Patrick Mayr
Bruno Märkl
Abbas Agaimy
Bernadette Kriening
Sebastian Dintner
Gerhard Schenkirsch
Regine Schneider-Stock
Publication date: 01-08-2019
Publisher: Springer Berlin Heidelberg
Keyword: Gastrointestinal Stromal Tumor
Published in: Langenbeck's Archives of Surgery / Issue 5/2019
Print ISSN: 1435-2443
Electronic ISSN: 1435-2451
DOI: https://doi.org/10.1007/s00423-019-01773-2

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

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 5/2019

Application-based management of perioperative anticoagulant therapy: description of POPACTApp

Critical appraisal of the modified ante situm liver resection

Prospective multi-center study of surgeon’s assessment of the gallbladder compared to histopathological examination to detect incidental malignancy

Re-operations for early postoperative complications after CRS and HIPEC: indication, timing, procedure, and outcome

Is curative gastrectomy justified for gastric cancer with cytology positive as the only stage IV factor?

Complete mesocolic excision does not increase short-term complications in laparoscopic left-sided colectomies: a comparative retrospective single-center study