DOI QR코드

DOI QR Code

Does Immunohistochemistry Provide Additional Prognostic Data in Gastrointestinal Stromal Tumors?

  • Demir, Lutfiye (Department of Medical Oncology, Ataturk Training and Research Hospital, Izmir Katip Celebi University) ;
  • Ekinci, Nese (Department of Pathology, Ataturk Training and Research Hospital, Izmir Katip Celebi University) ;
  • Erten, Cigdem (Department of Medical Oncology, Ataturk Training and Research Hospital, Izmir Katip Celebi University) ;
  • Kucukzeybek, Yuksel (Department of Medical Oncology, Ataturk Training and Research Hospital, Izmir Katip Celebi University) ;
  • Alacacioglu, Ahmet (Department of Medical Oncology, Ataturk Training and Research Hospital, Izmir Katip Celebi University) ;
  • Somali, Isil (Department of Medical Oncology, Institute of Oncology, Dokuz Eylul University) ;
  • Can, Alper (Department of Medical Oncology, Ataturk Training and Research Hospital, Izmir Katip Celebi University) ;
  • Dirican, Ahmet (Department of Medical Oncology, Ataturk Training and Research Hospital, Izmir Katip Celebi University) ;
  • Bayoglu, Vedat (Department of Medical Oncology, Ataturk Training and Research Hospital, Izmir Katip Celebi University) ;
  • Akyol, Murat (Department of Medical Oncology, Ataturk Training and Research Hospital, Izmir Katip Celebi University) ;
  • Cakalagaoglu, Fulya (Department of Pathology, Ataturk Training and Research Hospital, Izmir Katip Celebi University) ;
  • Tarhan, Mustafa Oktay (Department of Medical Oncology, Ataturk Training and Research Hospital, Izmir Katip Celebi University)
  • Published : 2013.08.30

Abstract

Background: To investigate the predictive and prognostic effects of clinicopathologic and immunohistochemical (IHC) features in patients with gastrointestinal stromal tumours (GISTs). Materials and Methods: Fifty-six patients who were diagnosed with GIST between 2002 and 2012 were retrospectively evaluated. Relationships between clinicopathologic/immunohistochemical factors and prognosis were investigated. Results: Median overall survival (OS) of the whole study group was 74.9 months (42.8-107.1 months), while it was 95.2 months in resectable and 44.7 months in metastatic patients respectively (p=0.007). Epitheliolid tumor morphology was significantly associated with shortened OS as compared to other histologies (p=0.001). SMA(+) tumours were significantly correlated with low (<10/50HPF) mitotic activity (p=0.034). Moreover, SMA(+) patients tended to survive longer and had significantly longer disease-free survival (DFS) times than SMA (-) patients (37.7 months vs 15.9 months; p=0.002). High Ki-67 level (${\geq}30%$) was significantly associated with shorter OS (34 vs 95.2 months; 95%CI; p=0.001). CD34 (-) tumours were significantly associated with low proliferative tumours (Ki-67<%10) (p=0.026). Median PFS (progression-free survival) of the patients who received imatinib was 36 months (27.7-44.2 months). CD34 (-) patients had significantly longer PFS times than that of negative tumours; (50.8 vs 29.8 months; p=0.045). S100 and desmin expression did not play any role in predicting the prognosis of GISTs. Multivariate analysis demonstrated that ${\geq}10/50HPF$ mitotic activity/HPF was the only independent factor for risk of death in GIST patients. Conclusions: Despite the negative prognostic and predictive effect of high Ki-67 and CD34 expression, mitotic activity remains the strongest prognostic factor in GIST patients. SMA positivity seems to affect GIST prognosis positively. However, large-scale, multicenter studies are required to provide supportive data for these findings.

Keywords

References

  1. Aoyagi K, Kouhuji K, Yano S, et al (2009). Malignant potential of gastrointestinal stromal tumor of the stomach. Int Surg, 94, 1-9.
  2. Bertin M, Angriman I, Scarpa M, et al (2007). Prognosis of gastrointestinal stromal tumors. Hepatogastroenterology, 54, 124-8.
  3. Bertucci F, Blesius A, Cassier PA, et al (2011). Prognostic factors for progression-free and overall survival in patients with advanced GIST treated with standard-dose imatinib: Results from the BFR14 phase III trial of the French Sarcoma Group. ASCO Meeting Abstracts, 29, 2056.
  4. Casali PG, Fumagalli E, Gronchi A (2012). Adjuvant therapy of gastrointestinal stromal tumors (GIST). Curr Treat Options Oncol, 13, 277-84. https://doi.org/10.1007/s11864-012-0198-0
  5. Chirieac LR, Trent JC, Steinert DM, et al (2006). Correlation of immunophenotype with progression-free survival in patients with gastrointestinal stromal tumors treated with imatinib mesylate. Cancer, 107, 2237-44. https://doi.org/10.1002/cncr.22226
  6. Chiu YC, Lin JW, Changchien CS, et al (2005). Clinicopathological characteristics and prognosis of patients with small intestinal stromal tumors. J Formos Med Assoc, 104, 905-12.
  7. Debiec-Rychter M, Sciot R, Le Cesne A, et al (2006). KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumors. Eur J Cancer, 42, 1093-103. https://doi.org/10.1016/j.ejca.2006.01.030
  8. Dematteo RP, Lewis JJ, Leung D, et al (2000). Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg, 231, 51-8. https://doi.org/10.1097/00000658-200001000-00008
  9. Dematteo RP, Gold JS, Saran L, et al (2008). Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST). Cancer, 112, 608-15. https://doi.org/10.1002/cncr.23199
  10. Demetri GD, van Oosterom AT, Garrett CR, et al (2006). Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet, 368, 1329-38. https://doi.org/10.1016/S0140-6736(06)69446-4
  11. Desaj J, Shankar S, Heinrich MC, et al (2007). Clonal evolution of resistance to imatinib in patients with metastatic gastrointestinal stromal tumors. Clin Cancer Res, 13, 5398-405. https://doi.org/10.1158/1078-0432.CCR-06-0858
  12. Eisenhauer EA, Therasse P, Bogaerts J, et al (2009). New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1). Eur J Cancer, 45, 228-47. https://doi.org/10.1016/j.ejca.2008.10.026
  13. Fletcher CD, Berman JJ, Corless C, et al (2002). Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol, 33, 459-65. https://doi.org/10.1053/hupa.2002.123545
  14. Fujimoto Y, Nakanishi Y, Yoshimura K, Shimoda T (2003). Clinicopathologic study of primary malignant gastrointestinal stromal tumor of the stomach, with special reference to prognostic factors: analysis of results in 140 surgically resected patients. Gastric Cancer, 6, 39-48. https://doi.org/10.1007/s101200300005
  15. Heinrich MC, Corless CL, Blanke CD, et al (2006). Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol, 24, 4764-74. https://doi.org/10.1200/JCO.2006.06.2265
  16. Heinrich MC, Marino-Enriquez A, Presnell A, et al (2012). Sorafenib inhibits many kinase mutations associated with drug-resistant gastrointestinal stromal tumors. Mol Cancer Ther, 11, 1770-80. https://doi.org/10.1158/1535-7163.MCT-12-0223
  17. Hirota S, Isozaki K, Moriyama Y, et al (1998). Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science, 279, 577-80. https://doi.org/10.1126/science.279.5350.577
  18. Hornick JL and Fletcher CD (2002). Immunohistochemical staining for KIT (CD117) in soft tissue sarcomas is very limited in distribution. Am J Clin Pathol, 117, 188-93. https://doi.org/10.1309/LX9U-F7P0-UWDH-8Y6R
  19. Hornick JL and Fletcher CD (2007). The role of KIT in the management of patients with gastrointestinal stromal tumors. Hum Pathol, 38, 679-87. https://doi.org/10.1016/j.humpath.2007.03.001
  20. Joensuu H (2008). Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Hum Pathol, 39, 1411-9. https://doi.org/10.1016/j.humpath.2008.06.025
  21. Kim KM, Kang DW, Moon WS, et al (2005). Gastrointestinal stromal tumors in Koreans: it's incidence and the clinical, pathologic and immunohistochemical findings. J Korean Med Sci, 20, 977-84. https://doi.org/10.3346/jkms.2005.20.6.977
  22. Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom JM (1998). Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol, 152, 1259-69.
  23. Koay MH, Goh YW, Iacopetta B, et al (2005). Gastrointestinal stromal tumors (GISTs): a clinicopathological and molecular study of 66 cases. Pathology, 37, 22-31. https://doi.org/10.1080/00313020400023628
  24. Koh Y, Lee HE, Oh DY, et al (2012). The lack of CD34 expression in gastrointestinal stromal tumors is related to cystic degeneration following imatinib use. Jpn J Clin Oncol, 42, 1020-7. https://doi.org/10.1093/jjco/hys138
  25. Li J, Gong JF, Wu AW, Shen L (2011). Post-operative imatinib in patients with intermediate or high risk gastrointestinal stromal tumor. Eur J Surg Oncol, 37, 319-24. https://doi.org/10.1016/j.ejso.2011.01.005
  26. Liang YM, Li XH, Chen W (2008). Roles of risk assessment and Ki-67 index in judging prognostic of gastrointestinal stromal tumors. Zhonghua Yi Xue Za Zhi, 88, 1041-5.
  27. Martin J, Poveda A, Llombart-Bosch A, et al (2005). Deletions affecting codon 557-558 of the c-KIT gene indicate a poor prognosis in patients with completely resected gastrointestinal stromal tumors: a study by the Spanish Group gor Sarcoma Research (GEIS). J Clin Oncol, 23, 6190-8. https://doi.org/10.1200/JCO.2005.19.554
  28. Mazurenko NN (2011). Prognostic relevance of genetic aberrations in gastrointestinal stromal tumors. ASCO GI Cancery Symposium, 29, 49.
  29. Miettinen M, Monihan JM, Sarlomo-Rikala M, et al (1999). Gastrointestinal stromal tumors/smooth muscle tumors (GISTs) primary in the omentum and mesentery: clinicopathologic and immunohistochemical study of 26 cases. Am J Surg Pathol, 23, 1109-18. https://doi.org/10.1097/00000478-199909000-00015
  30. Miettinen M, Lasota J (2001). Gastrointestinal stromal tumors- Definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch, 1, 1-12.
  31. Miettinen M, Makhlouf H, Sobin LH, Lasota J (2006). Gastrointestinal stromal tumors of the jejenum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. Am J Surg Pathol, 30, 477-89. https://doi.org/10.1097/00000478-200604000-00008
  32. Nagasako Y (2003). Evaluation of malignancy using Ki-67 labeling index for gastric stromal tumor. Gastric Cancer, 6, 168-72. https://doi.org/10.1007/s10120-003-0246-3
  33. 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, 821-9. https://doi.org/10.1002/cncr.20862
  34. Ogino J, Asanuma H, Hatanaka Y, et al (2013). Validity and reproducibility of Ki-67 assessment in gastrointestinal stromal tumors and leiomyosarcomas. Pathol Int, 63, 102-7. https://doi.org/10.1111/pin.12038
  35. Ohdaira H, Ohyama S, Yamaguchi T, et al (2005). Ki67 and tumor size as prognostic factors of gastrointestinal stromal tumors. JMAJ, 48, 586-92.
  36. Perez D, Demartines N, Meier K, Clavien PA (2007). Protien S100 as prognostic marker for gastrointestinal stromal tumors: a clinicopathological risk factor analysis. J Invest Surg, 20, 181-6. https://doi.org/10.1080/08941930701366349
  37. Reith JD, Goldblum JR, Lyles RH, Weiss SW (2000). Extragastrointestinal (soft tissue) stromal tumors: an analysis of 48 cases with emphasis on histologic predictors of outcome. Mod Pathol, 13, 577-85. https://doi.org/10.1038/modpathol.3880099
  38. Rubin BP, Heinrich MC, Corless CL (2007). Gastrointestinal stromal tumour. Lancet, 369, 1731-41. https://doi.org/10.1016/S0140-6736(07)60780-6
  39. Sanchez Hidalgo JM, Munoz Casares FC, Rufian Pena S, et al (2007). Gastrointestinal stromal tumors (GIST): factors predictive of survival after R0-cytoreduction. Rev Esp Enferm Dig, 99, 703-8.
  40. Sciot R, Debiec-Rychter M, Daugaard S, et al (2008). Distribution and prognostic value of histopathologic data and immunohistochemical markers in gastrointestinal stromal tumors (GISTs): An analysis of the EORTC phase III trial of treatment of metastatic GISTs with imatinib mesylate. Eur J Cancer, 44, 1855-60. https://doi.org/10.1016/j.ejca.2008.06.003
  41. Singer S, Rubin BP, Lux ML, et al (2002). Prognostic value of KIT mutation type, mitotic activity, an histologic subtype in gastrointestinal stromal tumors. J Clin Oncol, 20, 3898-905. https://doi.org/10.1200/JCO.2002.03.095
  42. Tornillo L and Terracciano LM (2006). An update on molecular genetics of gastrointestinal stromal tumors. J Clin Pathol, 59, 557-66. https://doi.org/10.1136/jcp.2005.031112
  43. van Oosterom AT, Judson I, Verweij J, et al (2001). European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumors: a phase I study. Lancet, 358, 1421-3. https://doi.org/10.1016/S0140-6736(01)06535-7
  44. Wang X (2002). Helpful parameter for malignant potential of gastrointestinal stromal tumors (GIST). Jpn J Clin Oncol, 9, 347-51.

Cited by

  1. A Rare Cause of Pneumoperitoneum: Perforated Gastrointestinal Stromal Tumor (GIST) vol.04, pp.05, 2014, https://doi.org/10.4236/ojgas.2014.45035
  2. Gastrointestinal Stromal Tumors in the 21<sup>st</sup> Century vol.05, pp.08, 2014, https://doi.org/10.4236/jct.2014.58086
  3. Are Rogerofenib and Nilotinib Effective for Advanced Gastrointestinal Stromal Tumor (GIST) Patients who have Already been Given Main Treatments? vol.16, pp.11, 2015, https://doi.org/10.7314/APJCP.2015.16.11.4801
  4. Gastrointestinal Stromal Tumors: A Clinicopathologic and Risk Stratification Study of 255 Cases from Pakistan and Review of Literature vol.16, pp.12, 2015, https://doi.org/10.7314/APJCP.2015.16.12.4873
  5. Giant gastrointestinal stromal tumour of rare sarcomatoid epithelioid subtype: Case study and literature review vol.21, pp.11, 2015, https://doi.org/10.3748/wjg.v21.i11.3388
  6. Back to the start: Evaluation of prognostic markers in gastrointestinal stromal tumors vol.4, pp.5, 2016, https://doi.org/10.3892/mco.2016.819
  7. Ki67 is a biological marker of malignant risk of gastrointestinal stromal tumors vol.96, pp.34, 2017, https://doi.org/10.1097/MD.0000000000007911
  8. Presence of intermediate filament protein synemin in select sarcomas vol.41, pp.2, 2018, https://doi.org/10.1080/01478885.2018.1438757