Approximately 80%-95%of gastrointestinal stromal tumors(GISTs)show positive staining for KIT,while the other 5%-20%show negative staining.If the tumor is negative for KIT,but is positive for CD34,a histological diagno...Approximately 80%-95%of gastrointestinal stromal tumors(GISTs)show positive staining for KIT,while the other 5%-20%show negative staining.If the tumor is negative for KIT,but is positive for CD34,a histological diagnosis is possible.However,if the tumor is negative for KIT,CD34,S-100,and SMA,a definitive diagnosis is often challenging.Recently,Discovered on GIST-1(DOG1)has received considerable attention as a useful molecule for the diagnosis of GIST.DOG1,a membrane channel protein,is known to be overexpressed in GIST.Because the sensitivity and specificity of DOG1 are higher than those of KIT,positive staining for DOG1has been reported,even in KIT-negative GISTs.KITnegative GISTs most commonly arise in the stomach and are mainly characterized by epithelioid features histologically.We describe our experience with a rare case of a KIT-negative GIST of the stomach that was diagnosed by positive immunohistochemical staining for DOG1 in a patient who presented with severe anemia.Our findings suggest that immunohistochemical staining for DOG1,in addition to gene analysis,is useful for the diagnosis of KIT-negative tumors that are suspected to be GISTs.展开更多
Mazur and Clark introduced the term ＂gastrointestinal stromal tumor＂ （GIST）. These tumors are thought to originate from mesenchymal stem cells that differentiate toward the interstitial cells of Cajal. Activation ...Mazur and Clark introduced the term ＂gastrointestinal stromal tumor＂ （GIST）. These tumors are thought to originate from mesenchymal stem cells that differentiate toward the interstitial cells of Cajal. Activation of c-kit or platelet-derived growth factor receptor alpha （PDGFRA） gene mutation has been shown to be a major force in GIST pathogenesis leading to down-stream phosphorylation of substrate proteins and subsequently activation of networks of signal transduction pathways that regulate cell proliferation,survival, apoptosis, motility and other important cell functions. Immunohistochemically, a great majority of GISTs show strong, diffuse c-kit expression. The diagnosis of GIST is currently based on morphologic features and immunohistochemical demonstration of c-kit （CD117）. However, in some cases c-kit immunoreactivity is weak or undetectable.展开更多
Gastrointestinal stromal tumors(GISTs) are the most common soft tissue sarcoma of the gastrointestinal tract,resulting from an activating mutation of stem cell factor receptor(KIT),and an activating mutation of the ho...Gastrointestinal stromal tumors(GISTs) are the most common soft tissue sarcoma of the gastrointestinal tract,resulting from an activating mutation of stem cell factor receptor(KIT),and an activating mutation of the homologous platelet-derived growth factor receptor alpha(PDGFRA) kinase.Most GISTs(90%-95%) are KIT-positive.About 5% of GISTs are truly negative for KIT expression.GISTs have been documented to resistant conventional chemotherapeutics.Due to the KIT activation that occurs in the majority of the cases,KIT inhibition is the primary treatment approach in the adjuvant treatment of metastatic GISTs.Imatinib mesylate is an oral agent that is a selective protein tyrosine kinase inhibitor of the KIT protein tyrosine kinase,and it has demonstrated clinical benefit and objective tumor responses in most GIST patients in phase Ⅱ and Ⅲ trials.The presence and the type of KIT or PDGFRA mutation are predictive of response to imatinib therapy in patients with advanced and metastatic disease.Molecular analysis in phaseⅠ-Ⅱ trials revealed significant differences in objective response,progression-free survival,and overall survival between GISTs with different kinase mutations.The aim of this letter is to touch on the need for exon mutation analysis for adjuvant treatment with imatinib in GIST patients.展开更多
Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients.The skeleton is frequently targeted by disseminated cancer cells and represents the sole site...Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients.The skeleton is frequently targeted by disseminated cancer cells and represents the sole site of spread in more than 80% of prostate cancer cases.Compatibility between select malignant phenotypes and the microenvironment of colonized tissues is broadly recognized as the culprit for the organ-tropism of cancer cells.Here,we review our recent studies showing that the expression of platelet-derived growth factor receptor alpha(PDGFR a) supports the survival and growth of prostate cancer cells in the skeleton and that the soluble fraction of bone marrow activates PDGFR a in a ligand-independent fashion.Finally,we offer pre-clinical evidence that this receptor is a viable target for therapy.展开更多
Platelet-derived growth factor receptor alpha （PDGFRct） is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whet...Platelet-derived growth factor receptor alpha （PDGFRct） is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whether there are differences in the distribution and morphol- ogy of oligodendrocyte precursor cells labeled by NG2 or PDGFRa in the developing neonatal rat brain remains unclear. In this study, by immunohistochemical staining, NG2 positive （NG2＋） cells were ubiquitous in the molecular layer, external pyramidal layer, internal pyramidal layer, and polymorphic layer of the cerebral cortex, and corpus callosum, external capsule, piriform cortex, and medial septal nucleus. NG2~ cells were stellate or fusiform in shape with long processes that were progressively decreased and shortened over the course of brain development. The distribution and morphology of PDGFRct positive （PDGFRa＋） cells were coincident with NG2＋ cells. The co- localization of NG2 and PDGFRu in the cell bodies and processes of some cells was confirmed by double immunofluorescence labeling. Moreover, cells double-labeled for NG2 and PDGFRa were predominantly in the early postnatal stage of development. The numbers of NG2＋/PDGFRa＋ cells and PDGFRa＋ cells decreased, but the number of NG2＋ cells increased from postnatal days 3 to 14 in the developing brain. In addition, amoeboid microglial cells of the corpus callosum, newborn brain macrophages in the normal developing brain, did not express NG2 or PDGFRu, but NG2 expression was detected in amoeboid microglia after hypoxia. The present results suggest that NG2 and PDGFRct are specific markers of oligodendrocyte precursor cells at different stages during early development. Additionally, the NG2 protein is involved in inflammatory and pathological processes of amoeboid microglial cells.展开更多
Sendur et al pointed out the attention on the importance of mutational analysis for adjuvant treatment of gastrointestinal stromal tumor (GIST) in an article published in World Journal of Gastroenterology . In particu...Sendur et al pointed out the attention on the importance of mutational analysis for adjuvant treatment of gastrointestinal stromal tumor (GIST) in an article published in World Journal of Gastroenterology . In particular, they suggested that the optimal dose and duration of adjuvant therapy could be defined by the mutational status of the primary disease. This comment would underline the importance of centralised laboratories, given the increasingly important role of molecular analysis in the work-flow of all GIST, and the need of retrospective analyses for subgroups population stratified for the mutational status from the available studies in the adjuvant setting, in order to define the role of mutational analysis in choosing the optimal dose and duration of adjuvant therapy.展开更多
Gastrointestinal(GI)stromal tumor is the most common mesenchymal neoplasm of the GI tract but also occurs with a lower frequency in extragastrointestinal regions and is called extragastrointestinal stromal tumor(EGIST...Gastrointestinal(GI)stromal tumor is the most common mesenchymal neoplasm of the GI tract but also occurs with a lower frequency in extragastrointestinal regions and is called extragastrointestinal stromal tumor(EGIST).We report an unusual case of EGIST presenting as a vaginal mass.A 41-year-old woman presented with a gradually enlarging vaginal mass for the last2 years.Physical examination revealed an elliptical,non-tender mass about 7.5 cm×7 cm in size in the posterior vaginal wall and was resected completely.Under histological examination,the tumor showed a spindle cell type with coagulation necrosis,hemorrhage and high mitotic count.Immunohistochemical analysis revealed tumor cells were positive for DOG1,CD117,CD34 and p53 protein.Ki-67 labeling was 8%.Genetic analysis showed a deletion of exon 11 of the c-kit gene at codons 557-558.EGISTs should be kept in mind in the differential diagnosis in patients presenting with solid mass of the vaginal wall.展开更多
Gastrointestinal stromal tumors(GISTs)represent a malignant gastrointestinal tumor of neurofibromatosis type 1(NF1)Von Recklinghausen disease.In the current case,we report a 27-year-old woman with NF1,who presented wi...Gastrointestinal stromal tumors(GISTs)represent a malignant gastrointestinal tumor of neurofibromatosis type 1(NF1)Von Recklinghausen disease.In the current case,we report a 27-year-old woman with NF1,who presented with a lower abdominal mass,symptomatic anaemia,and significant weight loss.We employed multiple approaches to assess the tumor behavior,including computed tomography(CT)scan,surgical tumor resection,histological and immunohistochemical analysis and gene sequencing.Additionally,the patient was given Imatinib mesylate(Gleevec)as adjuvant therapy.CT scan delineated a large thick wall cavity lesion connecting to the small bowel segment.Resection of the tumor yielded a mass of 17 cm×13 cm with achievement of safety margins.The diagnosis was GIST,confirmed by immunohistochemical expression of CD117,CD34,and Bcl-2.Sequencing revealed no mutations in either KIT or platelet-derived growth factor receptor-alpha,genes which are mutated in over 85%of sporadic GIST cases.Further,there was no evidence of recurrence,metastasis or metachronous GIST for over three years in our patient.From our analyses,we believe selective genotyping is advisable for high risk patients to predict potential tumor behavior.展开更多
文摘Approximately 80%-95%of gastrointestinal stromal tumors(GISTs)show positive staining for KIT,while the other 5%-20%show negative staining.If the tumor is negative for KIT,but is positive for CD34,a histological diagnosis is possible.However,if the tumor is negative for KIT,CD34,S-100,and SMA,a definitive diagnosis is often challenging.Recently,Discovered on GIST-1(DOG1)has received considerable attention as a useful molecule for the diagnosis of GIST.DOG1,a membrane channel protein,is known to be overexpressed in GIST.Because the sensitivity and specificity of DOG1 are higher than those of KIT,positive staining for DOG1has been reported,even in KIT-negative GISTs.KITnegative GISTs most commonly arise in the stomach and are mainly characterized by epithelioid features histologically.We describe our experience with a rare case of a KIT-negative GIST of the stomach that was diagnosed by positive immunohistochemical staining for DOG1 in a patient who presented with severe anemia.Our findings suggest that immunohistochemical staining for DOG1,in addition to gene analysis,is useful for the diagnosis of KIT-negative tumors that are suspected to be GISTs.
文摘Mazur and Clark introduced the term ＂gastrointestinal stromal tumor＂ （GIST）. These tumors are thought to originate from mesenchymal stem cells that differentiate toward the interstitial cells of Cajal. Activation of c-kit or platelet-derived growth factor receptor alpha （PDGFRA） gene mutation has been shown to be a major force in GIST pathogenesis leading to down-stream phosphorylation of substrate proteins and subsequently activation of networks of signal transduction pathways that regulate cell proliferation,survival, apoptosis, motility and other important cell functions. Immunohistochemically, a great majority of GISTs show strong, diffuse c-kit expression. The diagnosis of GIST is currently based on morphologic features and immunohistochemical demonstration of c-kit （CD117）. However, in some cases c-kit immunoreactivity is weak or undetectable.
文摘Gastrointestinal stromal tumors(GISTs) are the most common soft tissue sarcoma of the gastrointestinal tract,resulting from an activating mutation of stem cell factor receptor(KIT),and an activating mutation of the homologous platelet-derived growth factor receptor alpha(PDGFRA) kinase.Most GISTs(90%-95%) are KIT-positive.About 5% of GISTs are truly negative for KIT expression.GISTs have been documented to resistant conventional chemotherapeutics.Due to the KIT activation that occurs in the majority of the cases,KIT inhibition is the primary treatment approach in the adjuvant treatment of metastatic GISTs.Imatinib mesylate is an oral agent that is a selective protein tyrosine kinase inhibitor of the KIT protein tyrosine kinase,and it has demonstrated clinical benefit and objective tumor responses in most GIST patients in phase Ⅱ and Ⅲ trials.The presence and the type of KIT or PDGFRA mutation are predictive of response to imatinib therapy in patients with advanced and metastatic disease.Molecular analysis in phaseⅠ-Ⅱ trials revealed significant differences in objective response,progression-free survival,and overall survival between GISTs with different kinase mutations.The aim of this letter is to touch on the need for exon mutation analysis for adjuvant treatment with imatinib in GIST patients.
基金supported by the W.W. Smith Charitable Trust and Department of Defense (CDMRP) grants W81XWH-09-1-0593 and W81XWH-09-1-0724
文摘Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients.The skeleton is frequently targeted by disseminated cancer cells and represents the sole site of spread in more than 80% of prostate cancer cases.Compatibility between select malignant phenotypes and the microenvironment of colonized tissues is broadly recognized as the culprit for the organ-tropism of cancer cells.Here,we review our recent studies showing that the expression of platelet-derived growth factor receptor alpha(PDGFR a) supports the survival and growth of prostate cancer cells in the skeleton and that the soluble fraction of bone marrow activates PDGFR a in a ligand-independent fashion.Finally,we offer pre-clinical evidence that this receptor is a viable target for therapy.
基金supported by grants from the National Natural Science Foundation of China,No.31100769
文摘Platelet-derived growth factor receptor alpha （PDGFRct） is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whether there are differences in the distribution and morphol- ogy of oligodendrocyte precursor cells labeled by NG2 or PDGFRa in the developing neonatal rat brain remains unclear. In this study, by immunohistochemical staining, NG2 positive （NG2＋） cells were ubiquitous in the molecular layer, external pyramidal layer, internal pyramidal layer, and polymorphic layer of the cerebral cortex, and corpus callosum, external capsule, piriform cortex, and medial septal nucleus. NG2~ cells were stellate or fusiform in shape with long processes that were progressively decreased and shortened over the course of brain development. The distribution and morphology of PDGFRct positive （PDGFRa＋） cells were coincident with NG2＋ cells. The co- localization of NG2 and PDGFRu in the cell bodies and processes of some cells was confirmed by double immunofluorescence labeling. Moreover, cells double-labeled for NG2 and PDGFRa were predominantly in the early postnatal stage of development. The numbers of NG2＋/PDGFRa＋ cells and PDGFRa＋ cells decreased, but the number of NG2＋ cells increased from postnatal days 3 to 14 in the developing brain. In addition, amoeboid microglial cells of the corpus callosum, newborn brain macrophages in the normal developing brain, did not express NG2 or PDGFRu, but NG2 expression was detected in amoeboid microglia after hypoxia. The present results suggest that NG2 and PDGFRct are specific markers of oligodendrocyte precursor cells at different stages during early development. Additionally, the NG2 protein is involved in inflammatory and pathological processes of amoeboid microglial cells.
文摘Sendur et al pointed out the attention on the importance of mutational analysis for adjuvant treatment of gastrointestinal stromal tumor (GIST) in an article published in World Journal of Gastroenterology . In particular, they suggested that the optimal dose and duration of adjuvant therapy could be defined by the mutational status of the primary disease. This comment would underline the importance of centralised laboratories, given the increasingly important role of molecular analysis in the work-flow of all GIST, and the need of retrospective analyses for subgroups population stratified for the mutational status from the available studies in the adjuvant setting, in order to define the role of mutational analysis in choosing the optimal dose and duration of adjuvant therapy.
文摘Gastrointestinal(GI)stromal tumor is the most common mesenchymal neoplasm of the GI tract but also occurs with a lower frequency in extragastrointestinal regions and is called extragastrointestinal stromal tumor(EGIST).We report an unusual case of EGIST presenting as a vaginal mass.A 41-year-old woman presented with a gradually enlarging vaginal mass for the last2 years.Physical examination revealed an elliptical,non-tender mass about 7.5 cm×7 cm in size in the posterior vaginal wall and was resected completely.Under histological examination,the tumor showed a spindle cell type with coagulation necrosis,hemorrhage and high mitotic count.Immunohistochemical analysis revealed tumor cells were positive for DOG1,CD117,CD34 and p53 protein.Ki-67 labeling was 8%.Genetic analysis showed a deletion of exon 11 of the c-kit gene at codons 557-558.EGISTs should be kept in mind in the differential diagnosis in patients presenting with solid mass of the vaginal wall.
文摘Gastrointestinal stromal tumors(GISTs)represent a malignant gastrointestinal tumor of neurofibromatosis type 1(NF1)Von Recklinghausen disease.In the current case,we report a 27-year-old woman with NF1,who presented with a lower abdominal mass,symptomatic anaemia,and significant weight loss.We employed multiple approaches to assess the tumor behavior,including computed tomography(CT)scan,surgical tumor resection,histological and immunohistochemical analysis and gene sequencing.Additionally,the patient was given Imatinib mesylate(Gleevec)as adjuvant therapy.CT scan delineated a large thick wall cavity lesion connecting to the small bowel segment.Resection of the tumor yielded a mass of 17 cm×13 cm with achievement of safety margins.The diagnosis was GIST,confirmed by immunohistochemical expression of CD117,CD34,and Bcl-2.Sequencing revealed no mutations in either KIT or platelet-derived growth factor receptor-alpha,genes which are mutated in over 85%of sporadic GIST cases.Further,there was no evidence of recurrence,metastasis or metachronous GIST for over three years in our patient.From our analyses,we believe selective genotyping is advisable for high risk patients to predict potential tumor behavior.
