c-kit, PDGFRA의 면역조직화학적 발현 양상과 변이 분석을 통한 위장관기질종양 진단의 접근
An Approach to Diagnosing Gastrointestinal Stromal Tumors Using Immunohistochemistry of c-kit and PDGFRA with Molecular Analysis
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Background : Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract. Recently, many methods for the diagnosis of GIST have been developed including molecular diagnosis. Methods : We selected 90 cases of GIST that had presented at Kyungpook National University Hospital between 1998 and 2007. Tissue microarrays were made using core areas of tumor tissues. Immunohistochemical staining for c-kit, protein kinase C-theta, and platelet-derived growth factor receptor alpha (PDGFRA) was done. Direct sequencing of hot spot exonal areas for c-kit and PDGFRA were done using extracted DNAs of all 90 paraffin block tissues. Results : Among the 90 cases, 83.3% (75/90) were c-kit positive, 16.6% (15/90) were c-kit negative, 93.3% (84/90) were PDGFRA positive, and 6.6% (6/90) cases were PDGFRA negative. Fifteen cases of c-kit negative GIST included 1 case of PDGFRA negative and 5 cases of PDGFRA negative GIST were ckit positive. The one case in which both c-kit and PDGFRA were negative, showed a c-kit mutation in exon 11. Conclusions : Combined immunohistochemical staining of c-kit, discovered on GIST 1 (DOG1) and PDGFRA is helpful for the diagnosis of GIST. When all staining tests are negative for immunoreactivity, c-kit mutation analysis for exon 11, 9 should be done. Genotyping of kit and PDGFRA do not need to be examined initially, if it is only for the diagnosis of GIST.
Abstract
Background : Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract. Recently, many methods for the diagnosis of GIST have been developed including molecular diagnosis. Methods : We selected 90 cases of GIST that had presented at Kyungpook National University Hospital between 1998 and 2007. Tissue microarrays were made using core areas of tumor tissues. Immunohistochemical staining for c-kit, protein kinase C-theta, and platelet-derived growth factor receptor alpha (PDGFRA) was done. Direct sequencing of hot spot exonal areas for c-kit and PDGFRA were done using extracted DNAs of all 90 paraffin block tissues. Results : Among the 90 cases, 83.3% (75/90) were c-kit positive, 16.6% (15/90) were c-kit negative, 93.3% (84/90) were PDGFRA positive, and 6.6% (6/90) cases were PDGFRA negative. Fifteen cases of c-kit negative GIST included 1 case of PDGFRA negative and 5 cases of PDGFRA negative GIST were ckit positive. The one case in which both c-kit and PDGFRA were negative, showed a c-kit mutation in exon 11. Conclusions : Combined immunohistochemical staining of c-kit, discovered on GIST 1 (DOG1) and PDGFRA is helpful for the diagnosis of GIST. When all staining tests are negative for immunoreactivity, c-kit mutation analysis for exon 11, 9 should be done. Genotyping of kit and PDGFRA do not need to be examined initially, if it is only for the diagnosis of GIST.
참고문헌 (30)
- Fletcher CD, "Diagnosis of gastrointestinal stromal tumors:a consensus approach", Hum Pathol, 33, pp.459~465 (2002)
- Kyoung-Mee Kim, "Gastrointestinal Stromal Tumors in Koreans:It's Incidence and the Clinical,Pathologic and Immunohistochemical Findings", Journal of Korean Medical Science, 20(6), pp.977~984 (2005), 대한의학회
- 강동욱, "위장관 간질종양에서 c-kit유전자 돌연변이 및 면역조직화학적 발현", The Korean Journal of Pathology, 37(4), pp.246~254 (2003), 대한병리학회
- 석상희, "위와 소장에서 발생한 위장관기질종양의 예후 비교분석 - 단일기관 126예를 대상으로 한 후향적 연구 -", The Korean Journal of Pathology, 42(6), pp.335~343 (2008), 대한병리학회
- Kang YK, "Clinical practice guideline for adequate diagnosis and effective treatment of gastrointestinal stromal tumor in Korea", J Korean Med Assoc, 50, pp.830~841 (2007)
- Rubin BP, "Gastrointestinal stromal tumours:an update", Histopathology, 48, pp.83~96 (2006)
- Fletcher JA, "KIT mutations in GIST", Curr Opin Genet Dev, 17, pp.3~7 (2007)
- Hornick JL, "The role of KIT in the management of patients with gastrointestinal stromal tumors", Hum Pathol, 38, pp.679~687 (2007)
- Miettinen M, "Gastrointestinal stromal tumors:review on morphology,molecular pathology,prognosis,and differential diagnosis", Arch Pathol Lab Med, 130, pp.1466~1478 (2006)
- Blay JY, "Consensus meeting for the management of gastrointestinal stromal tumors:report of the GIST Consensus Conference of 20-21 March 2004,under the auspices of ESMO", Ann Oncol, 16, pp.566~578 (2005)
- Kitamura Y, "Gastrointestinal stromal tumors:past,present,and future", J Gastroenterol, 43, pp.499~508 (2008)
- Streutker CJ, "Interstitial cells of Cajal in health and disease.Part I:normal ICC structure and function with associated motility disorders", Histopathology, 50, pp.176~189 (2007)
- Streutker CJ, "Interstitial cells of Cajal in health and disease.Part II:ICC and gastrointestinal stromal tumours", Histopathology, 50, pp.190~202 (2007)
- Tornillo L, "Patterns of gene amplification in gastrointestinal stromal tumors(GIST)", Lab Invest, 85, pp.921~31 (2005)
- Wong NA, "KIT and PDGFR alpha mutational analyses of mixed cell-type gastrointestinal stromal tumours", Histopathology, 51, pp.758~762 (2007)
- Gomes AL, "Molecular analysis of c-Kit and PDGFRA in GISTs diagnosed by EUS", Am J Clin Pathol, 127, pp.89~96 (2007)
- Peterson MR, "Strong PDGFRA positivity is seen in GISTs but not in other intra-abdominal mesenchymal tumors:immunohistochemical and mutational analyses", Appl Immunohistochem Mol Morphol, 14, pp.390~396 (2006)
- Zheng S, "Analysis of mutation and expression of c-kit and PDGFR-alpha gene in gastrointestinal stromal tumor", Hepatogastroenterology, 54, pp.2285~2290 (2007)
- Motegi A, "PKC theta,a novel immunohistochemical marker for gastrointesti nal stromal tumors(GIST),especially useful for identifying KITnegative tumors", Pathol Int, 55, pp.106~112 (2005)
- Blay P, "Protein kinase C theta is highly expressed in gastrointestinal stromal tumors but not in other mesenchymal neoplasias", Clin Cancer Res, 10, pp.4089~4095 (2004)
- Espinosa I, "A novel monoclonal antibody against DOG1 is a sensitive and specific marker for gastrointestinal stromal tumors", Am J Surg Pathol, 32, pp.210~218 (2008)
- Miwa S, "Mutation assay of the novel gene DOG1 in gastrointestinal stromal tumors(GISTs)", J Gastroenterol, 43, pp.531~537 (2008)
- Steinert DM, "Expression of Bcl-2 in gastrointestinal stromal tumors:correlation with progression-free survival in 81 patients treated with imatinib mesylate", Cancer, 106, pp.1617~1623 (2006)
- Lee HE, "Characteristics of KIT-negative gastrointestinal stromal tumours and diagnostic utility of protein kinase C theta immunostaining", J Clin Pathol, 61, pp.722~729 (2008)
- Kim KM, "PKC theta expression in gastrointestinal stromal tumor", Mod Pathol, 19, pp.1480~1486 (2006)
- Turner MS, "Best practices in diagnostic immunohistochemistry:spindle cell neoplasms of the gastrointestinal tract", Arch Pathol Lab Med, 133, pp.1370~1374 (2009)
- Kang HJ, "Correlation of KIT and plateletderived growth factor receptor alpha mutations with gene activation and expression profiles in gastrointestinal stromal tumors", Oncogene, 24, pp.1066~1074 (2005)
- Subramanian S, "Gastrointestinal stromal tumors(GISTs)with KIT and PDGFRA mutations have distinct gene expression profiles", Oncogene, 23, pp.7780~7790 (2004)
- He HY, "Status and clinical implication of c-kit and PDGFRA mutations in 165 cases of gastrointestinal stromal tumor(GIST)", Zhonghua Bing Li Xue Za Zhi, 35, pp.262~266 (2006)
- Du CY, "The analysis of status and clinical implication of KIT and PDGFRA mutations in gastrointestinal stromal tumor(GIST)", J Surg Oncol, 98, pp.175~178 (2008)