Jerzy Lasota

..GISTs with secondary mutations in exon 13 and 14 are sensitive to sunitinib, another tyrosine kinase inhibitor. KIT and PDGFRA genotyping is important for GIST diagnosis and assessment of sensitivity to tyrosine kinase inhibitors...

..4 months. Based on these findings, we conclude that presence of homozygous KIT exon 11 mutations is associated with malignant course of disease and should be considered an adverse prognostic marker in GISTs...

..An isolated LOH at D22S425 was equally found in both benign and malignant tumors. These observations may suggest that LOHs on chromosome 22q in GISTs play a role in early stages of tumor formation as well as in late tumor progression...

..In four cases with moderate or high malignant potential GISTs, a long-term follow-up (average 235.5 months) showed favorable course of disease...

..Based on long-term follow-up (average 135 months), a majority (83.5%) of GISTs with PDGFRA mutations followed a benign course...

..The latter is also true for all KIT exon 17 mutant GISTs...

..Cytogenetic and molecular genetic alterations identified in various mesenchymal tumors are often valuable for diagnosis, prognosis, and treatment strategies...

..Use of the PCR assay amplifying the specific region affected by duplications and yielding 129 bp in wild-type KIT can substantially improve the detection of these mutations in formalin-fixed, paraffin-embedded GISTs...

..Moreover, KIT codon 558 insertions might indicate an increased risk of malignant behavior for gastric gastrointestinal stromal tumors...

..Mutation genotyping is a tool in GIST diagnosis and in assessment of sensitivity to kinase inhibitors. This is a US government work. There are no restrictions on its use...

..The coexistence of NF2 gene mutations and LOH at the NF2 locus indicates that the NF2 tumor suppressor gene is altered in PNTs by the two-hit mechanism...

..We also suggest that these polyps may develop from earlier described PDGFRA-positive mesenchymal cells distributed along the villus membrane after oncogenic PDGFRA activation...

..However, lack of NF2 alterations strongly supports the hypothesis that GI schwannomas represent a morphologically and genetically distinct group of peripheral nerve sheath tumors that are different from conventional schwannomas...

..This suggests that presence of these IDTs may define a clinicopathologically favorable subset of GISTs. The consequence of these mutations to KIT signaling should be investigated...

..5%, based on evaluation of 700 KIT exon 11 mutants. Molecular events leading to formation of deletion-inversions remain elusive and should be studied further...

..GISTs carrying 1530ins6 occur exclusively in the intestinal location, and a great majority of these tumors follow a malignant course...

..KIT positive Cajal cells were not found in normal omental tissues failing to support the presence of these ancestral cells for GIST in the omentum...

..DOG1 should be added into the diagnostic panel evaluating GI and other abdominal tumors, but limitations in its sensitivity and specificity should be recognized...

..The great majority of duodenal mesenchymal tumors are GISTs, which have a spectrum from small indolent tumors to overt sarcomas. LMs and LMSs are rare...

..Genetic markers, including DNA-copy number changes, telomerase activity, and KIT mutation status, may be useful in more accurately identifying tumors with malignant potential...

..There were no PDGFRA exon 12 or 8 mutations. Systematic data on prognosis of small intestinal GISTs of various size and mitotic activity categories can be helpful in management and surveillance of patients with these tumors...

..They are believed to originate from interstitial cells of Cajal or related stem cells...

..Plexiform fibromyxoma is a distinctive benign gastric antral neoplasm that should be separated from GIST, nerve sheath tumors, and other fibromyxoid neoplasms...

..These tumors should be recognized as part of the spectrum of synovial sarcomas...

..5, 5, and 14 years. Because these tumors have some resemblance to blastomas of other organs, we propose the term "gastroblastoma" for this distinctive, at least low-grade malignant epitheliomesenchymal tumor of the stomach...

..The above results may be helpful for setting the criteria for adjuvant treatment such as Gleevec...

..Their pathogenesis may differ from that of adult GISTs because no KIT or PDGFRA mutations were found; connection with Carney triad seems infrequent despite demographic and histologic similarities...

..These tumors most commonly occur in the stomach and small intestine and encompass a clinical spectrum from benign to malignant. In the current study, the authors examined long-term follow-up data of 1892 GIST patients from the U.S...

..None of the 16 tumors from 15 patients had a KIT exon 9, 11, 13, or 17 or PDGFRA exon 12 or 18 mutation as is typically seen in sporadic GISTs, indicating that GISTs in NF1 patients have a different pathogenesis than sporadic GISTs...

..It should be distinguished from gastrointestinal stromal tumor and other mesenchymal tumors of the gastrointestinal tract, such as the S100 protein-positive gastrointestinal clear cell sarcoma and metastatic melanoma...

..Immunohistochemical demonstration of KIT, CD34, or protein kinase theta positivity helps to properly identify these tumors...

..The number of LMS cases is too small for stratification for risk assessment. True SMTs of small intestine should be separated from GISTs because of different pathogenesis and treatment...

..Functional analysis of the different c-kit mutations and their impact on the response to tyrosine kinase inhibitors are under intense investigation...

..Majority of these mutations are in-frame-deletions and missense mutations clustering in the 5'-end of juxtamembrane domain (exon 11). A rare mutation, an Ala502-Tyr503 duplication in exon 9, is specific for intestinal GISTs...

..These tumors are phenotypically similar to peripheral glomus tumors and differ from epithelioid GISTs...

..It is best avoided by employing a panel of leukocyte and epithelial antigens and by use of electron microscopy, if possible...

..Twenty-eight (97%) were positive for smooth muscle actin and 18 (62%) for desmin but none for CD117 and S-100. Both GISTs and true LMs occur in the GI tract of dogs. Both tumors have distinctive pathologic features...

..Intramural LMs are exceptional, and true LMSs are rare, and similar to colonic ones, often present as intraluminal polypoid masses that appear to have a better prognosis than GISTs with similar mitotic rates...

..Angiosarcomas and metastatic melanomas, both of which are often KIT-positive, should not be confused with GISTs...

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..More cases of nonhuman primate GISTs should be analyzed to discover the clinicopathologic spectrum of GISTs in these species...

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..These observations may reflect the different pathways leading to malignant transformation of GISTs...

..Global expression of K7 and K19 in mesotheliomas versus focal expression in monophasic and poorly differentiated SSs, and differential patterns of K14 expression may also be helpful...

..A classification based on both SDHB expression status and KIT and PDGFRA mutation status characterize GISTs more accurately and allow subdivision of SDHB-positive tumors into different clinico-genetic categories...

..Microphthalmia transcription factor may be a valuable addition to the marker panel used in diagnosing melanoma, in combination with S100, TYR, and the other markers, but it is not present in cases of desmoplastic melanomas...

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..These findings suggest that accumulated genetic changes contribute to the pathogenesis of GANTs and that 22q13 loss may be a characteristic feature of these tumors...

..P16 loss is a common molecular abnormality in GISTs and might be used in routine diagnosis to identify patients with high-risk tumors...

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..Accurate subclassification of some of these lesions is difficult based on currently available techniques...

..The potential nonrandom association and causal relationship between GIST and other neoplasms remain to be investigated...

..To determine the prognostic relevance of p16INK4 alterations in GISTs, we investigated a larger group of GISTs and correlated the genetic findings with clinicopathological factors and patient survival...

..KIT and PDGFRA wild type was found in 15% of cases. Analysis of KIT and PDGFRA mutations is of significance for treatment with tyrosine kinase inhibitors, and may also have value when assessing the biological potential of GIST...

..Array CGH proved to be an effective tool for the identification of chromosome regions involved in the development and progression of GISTs...

..Thus, our findings emphasize the genetic differences between the two specimens and suggest that the occurrence of these two aggressive tumors of CNS in one family could be coincidental...