Gastrointestinal stromal tumor of the pancreas: case report with documentation of KIT gene mutation

Daum, Ondřej; Klečka, Jiří; Ferda, Jiří; Třeška, V.; Vaněček, Tomáš; Šíma, Radek; Mukenšnábl, Petr; Michal, Michal

doi:10.1007/s00428-004-1200-4

Cited by 56 publications

(32 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…No mutations were found in this case in exon 17. We searched for activation mutations in exon 9, 11, 13, and 17 of ckit gene and exon 12 and 18 of the PDGFRA gene, which are mutations often found in gastrointestinal stromal tumors [9]. While 75% of ovarian cases expressed KIT protein at immunohistochemical level, we found no activating mutations on any exons of c-kit and PDGFRA genes in any of MGSCTs in our series.…”

Section: Discussionmentioning

confidence: 55%

Mixed germ cell sex cord–stromal tumors of the testis and ovary. Morphological, immunohistochemical, and molecular genetic study of seven cases

et al. 2006

Self Cite

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 55%

Mixed germ cell sex cord–stromal tumors of the testis and ovary. Morphological, immunohistochemical, and molecular genetic study of seven cases

et al. 2006

Self Cite

View full text Add to dashboard Cite

“…10,40 Third, a true gastrointestinal stromal tumor of the pancreas harboring KIT mutations has been reported. 41 It is also interesting to note that the stromal cells of a pancreatic hamartoma also coexpressed KIT and CD34. 42 Coexpression of KIT and CD34 is a feature of interstitial cell of Cajal of both the intestine and the pancreas.…”

Section: Discussionmentioning

confidence: 99%

Positive immunohistochemical staining of KIT in solid-pseudopapillary neoplasms of the pancreas is not associated with KIT/PDGFRA mutations

et al. 2006

View full text Add to dashboard Cite

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 450% 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.

show abstract

“…Spindle cell tumors similar to GIST have been reported in the extra-gastrointestinal sites such as omentum, mesentery, urinary bladder, gallbladder, retroperitoneum, and pancreas [103][104][105][106][107][108][109][110] and their incidence is frequent enough to be separately categorized as extra-gastrointestinal stromal tumors (eGIST). They seem to be indistinguishable from GIST in their cytomorphology, c-Kit expression and genetic changes.…”

Section: Extra-gastrointestinal Stromal Tumors (Egist)mentioning

confidence: 99%

Interstitial Cells of Cajal (ICC) and Gastrointestinal Stromal Tumor (GIST): facts, speculations, and myths

Min

Leabu

2006

Journal of Cellular and Molecular Medicine

View full text Add to dashboard Cite

Interstitial cells of Cajal (ICC) is a peculiar cell network composed of cells having processes described by the eminent Spanish neuroanatomist of the 19 th century, S. Ramon y Cajal. ICC became a fascinating subject to many investigators and it is estimated that there are over 100 publications yearly on the subject related to ICC, in the last three years. Now it is widely accepted that ICC are pace maker cells of the gut and probable progenitor cells of gastrointestinal stromal tumors (GIST). Lately, interstitial Cajal-like cells (ICLC) are being found in various organs and their physiological role is still to be defined. We have reviewed the literature trying to evaluate the validity of the current concept and found that there are a few salient points to be considered. 1) There has been some important departure in defining the identity of ICC from the original criteria of Cajal. In particular, ICC with myoid feafures in intestinal smooth muscle layers (ICC-DPM) do not seem to fit to the original description of interstitial cell network by Cajal. We have also pointed out that the current reports assigning a pace maker role to ICC vastly depend on the scientific data on "ICC with myoid features", not on "fibroblast-like ICC", which are more abundant and easier to identify. 2) There seem to be an overwhelming amount of data proving the relationship between ICC and GIST. Both are known to express c-Kit and the ultrastructural characteristics seen in GIST roughly parallel those of ICC including minimal myoid differentiation seen in the majority of GIST, supporting the current concept that GIST are ICC tumors. 3) According to the original description of Cajal, ICC was not limited to the gut, suggesting an existence of ICC in other organs. The list of organs reported to contain ICC (currently identified by immunohistochemistry and electron microscopy) is ever growing and further studies are needed to define their identity and pathophysiologic role. 4). Recent data concerning gut development suggest that both c-Kit expressing ICC (fibroblasts-like as well as muscle-like) and gut muscle cells Their physiologic role was not clear at that time and even today, but Cajal speculated on a possible ancillary neural function, because of their anatomic proximity and morphologic similarity to nerves. In fact, interstitial cells of the gut are neither neural nor muscular, but are interposed between nerve and muscle cells. He considered that they might play a controlling function of the gut motility, and he thereby stimulated many investigators to study his concept. Consequently, a vast amount of data has been accumulated on 1) their existence, 2) the ultrastructural characterization of a possible pacemaker role in the gut, 3) electrophysiologic studies of peristalsis, 4) c-Kit as a molecular marker of ICC, and 5) as progenitor cells of gastrointestinal stromal tumors (GIST). The data thus far accumulated is vast and complex, but has promulgated the definition and identification of ICC [19].In recent years, much interesti...

show abstract

Gastrointestinal stromal tumor of the pancreas: case report with documentation of KIT gene mutation

Cited by 56 publications

References 9 publications

Mixed germ cell sex cord–stromal tumors of the testis and ovary. Morphological, immunohistochemical, and molecular genetic study of seven cases

Mixed germ cell sex cord–stromal tumors of the testis and ovary. Morphological, immunohistochemical, and molecular genetic study of seven cases

Positive immunohistochemical staining of KIT in solid-pseudopapillary neoplasms of the pancreas is not associated with KIT/PDGFRA mutations

Interstitial Cells of Cajal (ICC) and Gastrointestinal Stromal Tumor (GIST): facts, speculations, and myths

Contact Info

Product

Resources

About