Positive immunohistochemical staining of KIT in solid-pseudopapillary neoplasms of the pancreas is not associated with KIT/PDGFRA mutations Journal Article
| Authors: | Cao, D.; Antonescu, C.; Wong, G.; Winter, J.; Maitra, A.; Adsay, N. V.; Klimstra, D. S.; Hruban, R. H. |
| Article Title: | Positive immunohistochemical staining of KIT in solid-pseudopapillary neoplasms of the pancreas is not associated with KIT/PDGFRA mutations |
| Abstract: | Solid-pseudopapillary neoplasms of the pancreas are uncommon neoplasms of low malignant potential and of uncertain histogenesis. A small percentage of patients develop metastatic disease and some succumb to disease. The management of patients with metastatic disease or unresectable tumor, and patients who are just not good surgical candidates is problematic. Novel therapy targets are needed. Successful treatment of metastatic and unresectable gastrointestinal stromal tumors with KIT kinase inhibitor, imatinib mesylate (Gleevec), makes it intriguing to look at the status of KIT in solid-pseudopapillary neoplasms of the pancreas. In this study, we investigated KIT expression in 50 solid-pseudopapillary neoplasms by immunohistochemical staining. Of the 50 (50%) solid-pseudopapillary neoplasms, 25 showed diffuse expression (in >50% neoplastic cells) of KIT and additional five (10%) cases showed focal staining (in 10-50% neoplastic cells). Expression of KIT was not associated with tumor behavior and prognosis. A subset of 11 cases showing diffuse KIT expression detected by immunohistochemical staining were further evaluated for the presence of activating mutations in KIT exons 9, 11, 13 and 17, and PDGFRA exons 12 and 18 using PCR amplification followed by direct sequencing. However, no KIT or PDGFRA mutations were identified in any of these 11 cases tested, suggesting that the overexpression of KIT is probably not due to activating mutations in KIT or PDGFRA. The exact mechanism of KIT overexpression in solid- pseudopapillary neoplasms remains to be elucidated. One possible mechanism is gene dose effect (increased copies of KIT gene). Experience in gastrointestinal stromal tumors and other tumors have shown that mutation-mediated activation of KIT or PDGFRA is a prerequisite for clinical response with imatinib mesylate. Thus, lack of mutations in KIT or PDGFRA in solid-pseudopapillary neoplasms suggests that imatinib mesylate is less likely to be effective in the treatment for patients with metastatic disease or unresectable tumor, and patients who are just not good surgical candidates. © 2006 USCAP, Inc All rights reserved. |
| Keywords: | immunohistochemistry; adolescent; adult; child; clinical article; controlled study; human tissue; protein expression; aged; middle aged; survival rate; unclassified drug; gene mutation; gene sequence; exon; mutation; pancreatic neoplasms; polymerase chain reaction; pancreas; gastrointestinal stromal tumor; proto-oncogene proteins c-kit; receptor, platelet-derived growth factor alpha; gene expression; carcinoma, papillary; tumor markers, biological; platelet derived growth factor receptor; protein tyrosine kinase; gene identification; cancer cell; pancreas tumor; molecular analysis; cell count; kit; dna mutational analysis; gene dosage; solid-pseudopapillary neoplasm; kit protein |
| Journal Title: | Modern Pathology |
| Volume: | 19 |
| Issue: | 9 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2006-09-02 |
| Start Page: | 1157 |
| End Page: | 1163 |
| Language: | English |
| DOI: | 10.1038/modpathol.3800647 |
| PUBMED: | 16778826 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 20" - "Export Date: 4 June 2012" - "CODEN: MODPE" - "Source: Scopus" |
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