J Korean Med Sci.  2010 Jun;25(6):853-862. 10.3346/jkms.2010.25.6.853.

Current Trends in the Epidemiological and Pathological Characteristics of Gastrointestinal Stromal Tumors in Korea, 2003-2004

• Cho MY
• Sohn JH
• Kim JM
• Kim KM
• Park YS
• Kim WH
• Jung JS
• Jung ES
• Jin SY
• Kang DY
• Park JB
• Park HS
• Choi YD
• Sung SH
• Kim YB
• Kim H
• Bae YK
• Kang M
• Chang HJ
• Chae YS
• Lee HE
• Park DY
• Lee YS
• Kang YK
• Kim HK
• Chang HK
• Hong SW
• Choi YH
• Shin O
• Gu M
• Kim YW
• Kim GI
• Chang SJ

• KMID: 2150863
• DOI: http://doi.org/10.3346/jkms.2010.25.6.853

Abstract

Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patient's survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patient's survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patient's survival, but the mechanism still needs to be clarified through future studies.

Keyword

Gastrointestinal Stromal Tumors; Epidemiology; Pathology; Prognosis

Figure

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  Fig. 1 Univariate survival analyses of variables: gender (A, P=0.026), age (B, P=0.006), location (C, P=0.000), tumor size (D, P=0.000) and mitosis (E, P=0.000) are significantly correlated with patient's survival.

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  Fig. 2 Univariate analysis of variables of microscopic findings: Tumor necrosis (A), vessel invasion (B), mucosal invasion (C) and histologic type (D) are significantly correlated with patient's survival (P=0.000, 0.000, 0.000, 0.016, respectively).

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  Fig. 3 Univariate analysis of variables of immunohistochemical findings: CD34 expression (A) inversely relates with a patient's survival (P=0.001) in contrast to poor survival of GISTs with S-100 protein expression (B) (P=0.000). However α-smooth muscle actin expression (C) is not correlated with patient's survival (P=0.573).

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  Fig. 4 Univariate survival analysis of variables of diagnostic criterias: Both of the NIH criteria (A) and the AFIP criteria (B) are significantly correlated with patient's survival (P=0.000 & P=0.000).

Reference

1. Schaldenbrand JD, Appelman HD. Solitary solid stromal gastrointestinal tumors in von Recklinghausen's disease with minimal smooth muscle differentiation. Hum Pathol. 1984. 15:229–232.

2. Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, Miettinen M, O'Leary TJ, Remotti H, Rubin BP, Shmookler B, Sobin LH, Weiss SW. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol. 2002. 33:459–465.

3. Miettinen M, Lasota J. Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch. 2001. 438:1–12.

4. Dematteo RP, Heinrich MC, El-Rifai WM, Demetri G. Clinical management of gastrointestinal stromal tumors: before and after sti-571. Hum Pathol. 2002. 33:466–477.

5. Kim KM, Kang DW, Moon WS, Park JB, Park CK, Sohn JH, Jeong JS, Cho MY, Jin SY, Choi JS, Kang DY. Pkctheta expression in gastrointestinal stromal tumor. Mod Pathol. 2006. 19:1480–1486.

6. Espinosa I, Lee CH, Kim MK, Rouse BT, Subramanian S, Montgomery K, Varma S, Corless CL, Heinrich MC, Smith KS, Wang Z, Rubin B, Nielsen TO, Seitz RS, Ross DT, West RB, Cleary ML, van de Rijn M. A novel monoclonal antibody against dog1 is a sensitive and specific marker for gastrointestinal stromal tumors. Am J Surg Pathol. 2008. 32:210–218.

7. Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffith DJ, Haley A, Town A, Demetri GD, Fletcher CD, Fletcher JA. Pdgfra activating mutations in gastrointestinal stromal tumors. Science. 2003. 299:708–710.

8. Miettinen M, Sobin LH, Sarlomo-Rikala M. Immunohistochemical spectrum of gists at different sites and their differential diagnosis with a reference to cd117 (kit). Mod Pathol. 2000. 13:1134–1142.

9. Nilsson B, Bumming P, Meis-Kindblom JM, Oden A, Dortok A, Gustavsson B, Sablinska K, Kindblom LG. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era--a population-based study in western Sweden. Cancer. 2005. 103:821–829.

10. Tryggvason G, Gislason HG, Magnusson MK, Jonasson JG. Gastrointestinal stromal tumors in Iceland, 1990-2003: the Icelandic gist study, a population-based incidence and pathologic risk stratification study. Int J Cancer. 2005. 117:289–293.

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

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

13. Hornick JL, Fletcher CD. The role of kit in the management of patients with gastrointestinal stromal tumors. Hum Pathol. 2007. 38:679–687.

14. Kim KM, Kang DW, Moon WS, Park JB, Park CK, Sohn JH, Jeong JS, Cho MY, Jin SY, Choi JS, Kang DY. Gastrointestinal stromal tumors in Koreans: it's incidence and the clinical, pathologic and immunohistochemical findings. J Korean Med Sci. 2005. 20:977–984.

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

16. Goettsch WG, Bos SD, Breekveldt-Postma N, Casparie M, Herings RM, Hogendoorn PC. Incidence of gastrointestinal stromal tumours is underestimated: results of a nation-wide study. Eur J Cancer. 2005. 41:2868–2872.

17. Steigen SE, Eide TJ. Trends in incidence and survival of mesenchymal neoplasm of the digestive tract within a defined population of northern Norway. APMIS. 2006. 114:192–200.

18. Miettinen M, El-Rifai W, H L Sobin L, Lasota J. Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: a review. Hum Pathol. 2002. 33:478–483.

19. Cho MY, Kang YK, Kim KM, Chang HK, Chang HJ, Chang MS, Kim JM, Kang DY, Park C, Sohn JH. Porposal for creating a guideline for cancer registration of the gastrointestinal tumors (i). Korean J Pathol. 2008. 42:140–150.

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

21. Hou YY, Lu SH, Zhou Y, Xu JF, Ji Y, Hou J, Qi WD, Shi Y, Tan YS, Zhu XZ. Predictive values of clinical and pathological parameters for malignancy of gastrointestinal stromal tumors. Histol Histopathol. 2009. 24:737–747.

22. Huang HY, Li CF, Huang WW, Hu TH, Lin CN, Uen YH, Hsiung CY, Lu D. 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. 141:748–756.

23. Lasota J, Kopczynski J, Sarlomo-Rikala M, Schneider-Stock R, Stachura T, Kordek R, Michal M, Boltze C, Roessner A, Stachura J, Miettinen M. Kit 1530ins6 mutation defines a subset of predominantly malignant gastrointestinal stromal tumors of intestinal origin. Hum Pathol. 2003. 34:1306–1312.

24. Antonescu CR, Sommer G, Sarran L, Tschernyavsky SJ, Riedel E, Woodruff JM, Robson M, Maki R, Brennan MF, Ladanyi M, DeMatteo RP, Besmer P. Association of kit exon 9 mutations with nongastric primary site and aggressive behavior: kit mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors. Clin Cancer Res. 2003. 9:3329–3337.

25. Park CK, Lee EJ, Kim M, Lim HY, Choi DI, Noh JH, Sohn TS, Kim S, Kim MJ, Lee HK, Kim KM. Prognostic stratification of high-risk gastrointestinal stromal tumors in the era of targeted therapy. Ann Surg. 2008. 247:1011–1018.

26. Miettinen M, Sobin LH, Lasota J. 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. 2005. 29:52–68.

27. Woodall CE 3rd, Brock GN, Fan J, Byam JA, Scoggins CR, McMasters KM, Martin RC 2nd. An evaluation of 2537 gastrointestinal stromal tumors for a proposed clinical staging system. Arch Surg. 2009. 144:670–678.

28. Agaimy A, Wunsch PH, Hofstaedter F, Blaszyk H, Rummele P, Gaumann A, Dietmaier W, Hartmann A. Minute gastric sclerosing stromal tumors (gist tumorlets) are common in adults and frequently show c-kit mutations. Am J Surg Pathol. 2007. 31:113–120.

29. Kawanowa K, Sakuma Y, Sakurai S, Hishima T, Iwasaki Y, Saito K, Hosoya Y, Nakajima T, Funata N. High incidence of microscopic gastrointestinal stromal tumors in the stomach. Hum Pathol. 2006. 37:1527–1535.

30. Steigen SE, Eide TJ, Wasag B, Lasota J, Miettinen M. Mutations in gastrointestinal stromal tumors--a population-based study from Northern Norway. APMIS. 2007. 115:289–298.