Among the current classifications, many authors consider the MSKCC prognostic nomogram more feasible in clinical practice than the other classifications, even though it was not faultless in predicting the RFS. Furthermore, the main limitation of MSKCC nomogram remains the nonlinear consideration of mitotic count. Laparoscopy should not be considered as a negative prognostic factor, if oncological radicality has been respected. A good staging is also important in small GIST to avoid over/undertreatment. EUS seems to be the most valid tool for the correct characterization of these tumors. Imatinib therapy is recommended in high-grade GIST. Some studies suggest that adjuvant imatinib therapy should be prolonged for at least 5 years in high-grade GISTs, because of prolonged RFS. Probably, risk scores should be enriched with other factors such as radiological signs and biological markers. There are several studies about new prognostic factors especially in biological field. These factors need to be further investigated in order to validate their use in risk stratification. The genetic landscape of GIST appears to be very heterogeneous; a deeper understanding of the molecular mechanism underlying GIST progression would hopefully improve risk assessment. What we can hope is a new prognostic classification based only on biological markers, which could be more reliable than current classifications.


The authors report no conflicts of interest in this work.

Alessandra Greco,1 Sabrina Rossi,Cesare Ruffolo,1 Bruno Pauletti,3 Angelo Paolo Dei Tos,2 Giovanni Morana,4 Marco Massani3
1IV Department of Surgery, Regional Hospital Treviso, Treviso, Italy; 2Pathology Department, University of Padova and Regional Hospital, Treviso, Italy; 3III Department of Surgery, Regional Hospital Treviso, Treviso, Italy; 4Surgical Department, Regional Hospital Treviso, Treviso, Italy 


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

2. Nishida T, Hirota S. Biological and clinical review of stromal tumors in the gastrointestinal tract. Histol Histopathol. 2000;15:1293–1301.

3. Joensuu H. Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Hum Pathol. 2008;39:1411–1419.

4. McWhinney SR, Pasini B, Stratakis CA; International Carney Triad and Carney-Stratakis Syndrome Consortium. Familial gastrointestinal stromal tumors and germ-line mutations. N Engl J Med. 2007;357(10):1054–1056.

5. Pasini B, Mcwhinney SR, Bei T, et al. Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD. Eur J Hum Genet. 2008;16(1):79–88.

6. Gasparotto D, Rossi S, Polano M, et al. Quadruple-negative GIST is a sentinel for unrecognized neurofibromatosis type 1 syndrome. Clin Cancer Res. 2017;23:273–282.

7. Rossi S, Gasparotto D, Cacciatore M, et al. Neurofibromin C terminus-specific antibody (clone NFC) is a valuable tool for the identification of NF1-inactivated GISTs. Mod Pathol. 2018;31(1):160–168.

8. Agaram NP, Wong GC, Guo T, et al. Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors. Gen Chrom Cancer. 2008;47:853–859.

9. Brenca M, Rossi S, Polano M, et al. Transcriptome sequencing identifies ETV6-NTRK3 as a gene fusion involved in GIST. J Pathol. 2016;238(4):543–549.

10. Shi E, Chmielecki J, Tang CM, et al. FGFR1 and NTRK3 actionable alterations in “Wild-Type” gastrointestinal stromal tumors. J Transl Med. 2016;14(1):339.

11. Florou V, Wilky BA, Trent JC. Latest advances in adult gastrointestinal stromal tumors. Future Oncol. 2017;13(24):2183–2193.

12. Wong NA. Gastrointestinal stromal tumours–an update for histopathologists. Histopathology. 2011;59(5):807–821.

13. Woodall CE, Brock GN, Fan J, et al. An evaluation of 2537 gastrointestinal stromal tumors for a proposed clinical staging system. Arch Surg. 2009;144(7):670–678.

14. Demetri GD, Benjamin RS, Blanke CD, et al. NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST)–update of the NCCN Clinical Practice Guidelines. J Natl Compr Canc Netw. 2007;5(Suppl 2):S1–S29.

15. Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol. 2006;23:70–83.

16. Huang HY, Li CF, Huang WW, et al. A modification of NIH consensus criteria to better distinguish the highly lethal subset of primary localized gastrointestinal stromal tumors: a subdivision of the original high-risk group on the basis of outcome. Surgery. 2007;141(6):748–756.

17. Chok AY, Goh BK, Koh YX, et al. Validation of the MSKCC gastrointestinal stromal tumor nomogram and comparison with other prognostication systems: single-institution experience with 289 patients. Ann Surg Oncol. 2015;22(11):3597–3605.

18. ESMO/European Sarcoma Network Working Group. Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25 Suppl 3:iii21–iii26.

19. Demetri GD, Benjamin RS, Blanke CD, et al. NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST)–update of the NCCN Clinical Practice Guidelines. J Natl Compr Canc Netw. 2007;5(Suppl 2):S1–S31.

20. Fletcher CD, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol. 2002;33(5):459–465.

21. Gold JS, Gönen M, Gutiérrez A, et al. Development and validation of a prognostic nomogram for recurrence-free survival after complete surgical resection of localised primary gastrointestinal stromal tumour: a retrospective analysis. Lancet Oncol. 2009;10(11):1045–1052.

22. Rossi S, Miceli R, Messerini L, et al. Natural history of imatinib-naive GISTs: a retrospective analysis of 929 cases with long-term follow-up and development of a survival nomogram based on mitotic index and size as continuous variables. Am J Surg Pathol. 2011;35(11):1646–1656.

23. Bischof DA, Kim Y, Behman R, et al. A nomogram to predict disease-free survival after surgical resection of GIST. J Gastrointest Surg. 2014;18(12):2123–2129.

24. Schmieder M, Henne-Bruns D, Mayer B, et al. Comparison of different risk classification systems in 558 patients with gastrointestinal stromal tumors after R0-resection. Front Pharmacol. 2016;7:504.

25. Belfiori G, Sartelli M, Cardinali L, et al. Risk stratification systems for surgically treated localized primary gastrointestinal stromal tumors (GIST). Review of literature and comparison of the three prognostic criteria: MSKCC Nomogram, NIH-Fletcher and AFIP-Miettinen. Ann Ital Chir. 2015;86(3):219–227.

26. Doyle LA, Hornick JL. Gastrointestinal stromal tumours: from KIT to succinate dehydrogenase. Histopathology. 2014;64(1):53–67.

27. Miettinen M, Fetsch JF, Sobin LH, Lasota J. Gastrointestinal stromal tumors in patients with neurofibromatosis 1: a clinicopathologic and molecular genetic study of 45 cases. Am J Surg Pathol. 2006;30(1):90–96.

28. Zhou C, Duan X, Zhang X, Hu H, Wang D, Shen J. Predictive features of CT for risk stratifications in patients with primary gastrointestinal stromal tumour. Eur Radiol. 2016;26(9):3086–3093.

29. Miyake KK, Nakamoto Y, Mikami Y, et al. The predictive value of preoperative 18F-fluorodeoxyglucose PET for postoperative recurrence in patients with localized primary gastrointestinal stromal tumour. Eur Radiol. 2016;26(12):4664–4674.

30. Tokumoto N, Tanabe K, Misumi T, Fujikuni N, Suzuki T, Ohdan H. The usefulness of preoperative 18FDG positron-emission tomography and computed tomography for predicting the malignant potential of gastrointestinal stromal tumors. Dig Surg. 2014;31(2):79–86.

31. Bertucci F, Finetti P, Mamessier E, et al. PDL1 expression is an independent prognostic factor in localized GIST. Oncoimmunology. 2015;4(5):e1002729.

32. Suehara Y, Kondo T, Seki K, et al. Pfetin as a prognostic biomarker of gastrointestinal stromal tumors revealed by proteomics. Clin Cancer Res. 2008;14(6):1707–1717.

33. Orita H. Pfetin as a risk factor of recurrence in gastrointestinal stromal tumors. BioMed Res Int. 2014;651935.

34. Huang KK. SETD2 histone modifier loss in aggressive GI stromal tumours. Gut. 2016;65:1960–1972.

35. Wang CJ, Zhang ZZ, Xu J, et al. SLITRK3 expression correlation to gastrointestinal stromal tumor risk rating and prognosis. World J Gastroenterol. 2015;21(27):8398–8407.

36. Gyvyte U. MiRNA profiling of gastrointestinal stromal tumors by next-generation sequencing. Oncotarget. 2017;8:37225–37238.

37. Li CF, Chuang IC, Liu TT, et al. Transcriptomic reappraisal identifies MGLL overexpression as an unfavorable prognosticator in primary gastrointestinal stromal tumors. Oncotarget. 2016;7(31):49986–49997.

38. Wozniak A, Rutkowski P, Schoffski P, et al. Tumor genotype is an independent prognostic factor in primary gastrointestinal stromal tumors of gastric origin: a European multicenter analysis based on ConticaGIST. Clin Cancer Res. 2014;20(23):6105–6116.

39. Rossi S, Gasparotto D, Miceli R, et al. KIT, PDGFRA, and BRAF mutational spectrum impacts on the natural history of imatinib-naive localized GIST: a population-based study. Am J Surg Pathol. 2015;39(7):922–930.

40. Alkhasawneh A, Reith JD, Toro TZ, et al. Interobserver variability of mitotic index and utility of PHH3 for risk stratification in gastrointestinal stromal tumors. Am J Clin Pathol. 2015;143(3):385–392.

41. Rizzo FM, Palmirotta R, Marzullo A, et al. Parallelism of DOG1 expression with recurrence risk in gastrointestinal stromal tumors bearing KIT or PDGFRA mutations. BMC Cancer. 2016;16:87.

42. Zhang Y, Gu ML, Zhou XX, Ma H, Yao HP, Ji F. Altered expression of ETV1 and its contribution to tumorigenic phenotypes in gastrointestinal stromal tumors. Oncol Rep. 2014;32(3):927–934.

43. Zhou Y, Hu W, Chen P, et al. Ki67 is a biological marker of malignant risk of gastrointestinal stromal tumors: a systematic review and meta-analysis. Medicine. 2017;96(34):34.

44. Stotz M, Liegl-Atzwanger B, Posch F, et al. Blood-based biomarkers are associated with disease recurrence and survival in gastrointestinal stroma tumor patients after surgical resection. PLoS One. 2016;11(7):e0159448.

45. Xue A, Gao X, Fang Y, et al. Incorporation of NLR into NIH stratification system increases predictive accuracy for surgically resected gastrointestinal stromal tumors. Acta Biochim Biophys Sin. 2017;49(2):179–185.

46. Hsiao CY, Yang CY, Lai IR, Chen CN, Lin MT. Laparoscopic resection for large gastric gastrointestinal stromal tumor (GIST): intermediate follow-up results. Surg Endosc. 2015;29(4):868–873.

47. Lin J, Huang C, Zheng C, et al. Laparoscopic versus open gastric resection for larger than 5cm primary gastric gastrointestinal stromal tumors (GIST): a size-matched comparison. Surg Endosc. 2014;28(9):2577–2583.

48. Piessen G, Lefèvre JH, Cabau M, et al. Laparoscopic versus open surgery for gastric gastrointestinal stromal tumors: what is the impact on postoperative outcome and oncologic results? Ann Surg. 2015;262(5):831–839.

49. Joensuu H, Eriksson M, Hall KS, et al. Risk factors for gastrointestinal stromal tumor recurrence in patients treated with adjuvant imatinib. Cancer. 2014;120(15):2325–2333.

50. Bischof DA, Dodson R, Jimenez MC, et al. Adherence to guidelines for adjuvant imatinib therapy for GIST: a multi-institutional analysis. J Gastrointest Surg. 2015;19(6):1022–1028.

51. Guérin A, Sasane M, Keir CH, et al. Physician underestimation of the risk of gastrointestinal stromal tumor recurrence after resection. JAMA Oncol. 2015;1(6):797–805.

52. Dematteo RP, Ballman KV, Antonescu CR, et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;373(9669):1097–1104.

53. Joensuu H, Eriksson M, Sundby Hall K, et al. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA. 2012;307(12):1265–1272.

54. Trent JC, Subramanian MP. Managing GIST in the imatinib era: optimization of adjuvant therapy. Expert Rev Anticancer Ther. 2014;14(12):1445–1459.

55. Lin JX, Chen QF, Zheng CH, et al. Is 3-years duration of adjuvant imatinib mesylate treatment sufficient for patients with high-risk gastrointestinal stromal tumor? A study based on long-term follow-up.  J Cancer Res Clin Oncol. 2017;143(4):727–734.

56. Casali PG, Le Cesne A, Poveda Velasco A, et al. Time to definitive failure to the first tyrosine kinase inhibitor in localized GI stromal tumors treated with imatinib as an adjuvant: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Intergroup Randomized Trial in Collaboration with the Australasian Gastro-Intestinal Trials Group, UNICANCER, French Sarcoma Group, Italian Sarcoma Group, and Spanish Group for Research on Sarcomas. J Clin Oncol. 2015;33(36):4276–4283.

57. Joensuu H, Wardelmann E, Sihto H, et al. Effect of KIT and PDGFRA mutations on survival in patients with gastrointestinal stromal tumors treated with adjuvant imatinib: an exploratory analysis of a randomized clinical trial. JAMA Oncol. 2017;3(5):602–609.

58. Agaimy A, Wünsch PH, Hofstaedter F, et al. Minute gastric sclerosing stromal tumors (GIST tumorlets) are common in adults and frequently show c-KIT mutations. Am J Surg Pathol. 2007;31(1):113–120.

59. Kawanowa K, Sakuma Y, Sakurai S, et al. High incidence of microscopic gastrointestinal stromal tumors in the stomach. Hum Pathol. 2006;37(12):1527–1535.

60. Rossi S, Gasparotto D, Toffolatti L, et al. Molecular and clinicopathologic characterization of gastrointestinal stromal tumors (GISTs) of small size. Am J Surg Pathol. 2010;34(10):1480–1491.

61. Coe TM, Fero KE, Fanta PT, et al. Population-based epidemiology and mortality of small malignant gastrointestinal stromal tumors in the USA. J Gastrointest Surg. 2016;20(6):1132–1140.

62. Nishida T, Hirota S, Yanagisawa A, et al. Clinical practice guidelines for gastrointestinal stromal tumor (GIST) in Japan: English version. Int J Clin Oncol. 2008;13(5):416–430.

63. Nishida T, Goto O, Raut CP, Yahagi N. Diagnostic and treatment strategy for small gastrointestinal stromal tumors. Cancer. 2016;122(20):3110–3118.

64. Palazzo L, Landi B, Cellier C, Cuillerier E, Roseau G, Barbier JP. Endosonographic features predictive of benign and malignant gastrointestinal stromal cell tumours. Gut. 2000;46(1):88–92.

65. Chak A, Canto MI, Rösch T, et al. Endosonographic differentiation of benign and malignant stromal cell tumors. Gastrointest Endosc. 1997;45(6):468–473.

66. Demetri GD, von Mehren M, Antonescu CR, et al. NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors. J Natl Compr Canc Netw. 2010;8(Suppl 2): S1–S10.

67. Agaimy A. Gastrointestinal stromal tumor (GIST) from risk stratification systems to the new TNM proposal: more questions than answers? A review emphasizing the need for a standardized GIST reporting. Int J Clin Exp Pathol. 2010;3(5):461–471.

Source: Gastrointestinal Cancer: Targets and Therapy.
Originally published December 3, 2018.