Molecular mechanism study of Shouhui Tongbian Capsules on promoting energy metabolism of gastrointestinal stromal cells / 中国中药杂志

Mechanism study was performed to explore how Shouhui Tongbian Capsules promotes energy metabolism of gastrointestinal stromal cells. In this study, gastrointestinal stromal cells line GIST-882 was used as the model to explore energy metabolism regulation effects of Shouhui Tongbian Capsules extract(10, 20, 50 and 100 μg·mL~(-1)) by measuring the cell proliferation, ATP level, mitochondrial membrane potential, and mitochondrial isocitrate dehydrogenase activity. Meanwhile, Western blot was used to detect the proteins expression of SCF/c-Kit and CDK2/cyclin A signaling pathways. Our results showed that Shouhui Tongbian Capsules promoted cell proliferation and increased ATP level of gastrointestinal stromal cells. In addition, Shouhui Tongbian Capsules obviously improved mitochondrial structural integrity, and increased mitochondrial membrane potential in GIST-882 cells. Mechanism study revealed that Shouhui Tongbian Capsules increased mitochondrial isocitrate dehydrogenase activity and up-regulated the proteins expression of SCF/c-Kit and CDK2/cyclin A signaling pathways. Collectively, our study indicated that Shouhui Tongbian Capsules promoted the energy metabolism for gastrointestinal stromal cells proliferation by activating mitochondrial isocitrate dehydrogenase to induce ATP production, as well as activating SCF/c-Kit and CDK2/cyclin A signaling pathways.

Effect of bisacodyl on rats with slow transit constipation

The effect of bisacodyl on the treatment of rats with slow transit constipation (STC) was studied. Forty-five female Wister rats were divided into control group, STC group, and STC bisacodyl group. The immunohistochemical method was used to determine interstitial cells of Cajal (ICC) and the expression of c-Kit protein. Body mass and the number of defecations were significantly decreased in the STC group compared with the control group on the 100th day after diphenoxylate administration, while dry weight of feces was significantly increased and the intestinal transit time was prolonged. There were significant differences in the number of defecations, dry weight of feces, and intestinal transit time among the three groups. The number of defecations was higher, dry weight of feces was lower, and intestinal transit time was shorter in the STC bisacodyl group compared to the STC group. In addition, ICC basement membrane dissolution occurred in the colon wall of the STC group. The connection between ICC and surrounding cells was destroyed, and the nucleus shrunken to different degrees. Moreover, c-Kit expression in the STC group was significantly lower than the control group. The connection between ICC and surrounding cells in the STC bisacodyl group was significantly stronger than the STC group, and the number of ICC and the expression of c-Kit were increased. Bisacodyl could reduce the severity of STC in rats by increasing the number of ICC and the expression of c-Kit.

Avaliação da via do c-kit no adenoma pleomórfico e carcinoma adenoide cístico das glândulas salivares: estudo da expressão das proteínas da via, das mutações e da regulação pós-transcricional do gene kit / c-Kit signaling cascade in pleomorphic adenoma and adenoid cystic carcinoma of salivary glands: evaluation of cascade proteins, mutations and post-transcriptional regulation of gene Kit

Introdução: As neoplasias das glândulas salivares têm amplo espectro histológico resultante da múltipla diferenciação celular tumoral. O adenoma pleomórfico (AP) e o carcinoma adenoide cístico (CAC) são as mais comuns neoplasias benignas e malignas provenientes do ducto intercalado, respectivamente, além de serem compostas por estruturas luminais e células mioepiteliais. Em estudo realizado previamente pelo nosso grupo, detectamos que a proteína c-kit está envolvida nos processos da morfogênese das glândulas salivares e no adenoma pleomórfico. A proteína c-Kit tem papel importante no desenvolvimento de muitos processos embrionários, incluindo a gametogênese, melanogênese e hematopoiese, e também na biologia de tumores. Sua ativação induz diversas respostas intracelulares através de cascatas de sinalização de vias como PI3K/AKT e MAPK. Em tumores da glândula salivar ainda há poucos estudos sobre as alterações do gene KIT e das proteínas relacionadas a sua via de sinalização, assim como sua regulação pós-transcricional, realizada principalmente por meio dos microRNAs. O presente estudo avaliou, em APs e CACs (a) a localização das proteínas das vias PI3K/AKT/mTOR e MAPK por meio da técnica de imunoistoquímica; (b) a expressão dos microRNAs 221 e 222, relacionados ao gene KIT (c) a associação dos achados laboratoriais com variáveis clínicas, patológicas e sobrevida. Resultados: Nos casos de AP a proteína c-Kit foi identificada em formações luminais e em raras células isoladas no parênquima tumoral. Já nos CAC, observou-se positividade na membrana das células ductais. Para a via de PI3K/AKT/mTOR, no AP, a proteína PI3K beta mostrou-se parcialmente positiva no citoplasma das células próximas à capsula tumoral, e as proteínas AKT e mTOR fosforiladas, foram expressas especialmente nas células epiteliais e em poucas células mioepiteliais. Já no CAC, a proteína PI3K beta e AKT fosforilada mostraram-se negativas na maioria dos casos, e a proteína mTOR fosforilada foi expressa no citoplasma das células epiteliais e em algumas células mioepiteliais. Para a via MAPK, as proteínas RAS, MEK-1 fosforilada e ERK 1/2 foram negativas na maioria dos AP e CAC; B-Raf e MEK-2 fosforilada foram observadas nas células luminais dos AP. Nos CAC, estruturas luminais neoplásicas foram positivas para a proteína MEK-2 fosforilada; B-Raf foi positivo nas células luminais e mioepiteliais. Além disso, os pacientes que expressaram as proteínas mTOR e MEK-2 fosforilada apresentaram sobrevida câncer-específica significativamente aumentada (p=0,040 e p=0,005, respectivamente). Na análise do microRNAs, a expressão do miR-221 foi variável nas 13 amostras analisadas, tendo baixa expressão em 30,77% dos casos, expressão normal em 38,46 e expressão aumentada em 30,77% dos casos. Já nos APs o miR-221 foi detectado em 19 amostras, sendo 36,84% com baixa expressão, 52,63% com expressão normal e expressão aumentada foi vista em 10,53% dos casos. A expressão do miR-222 foi detectada em 14 CACs, sendo que a maioria dos casos (8 casos ­ 57,1%) a expressão do miR-222 foi semelhante ao observado nas amostras não neoplásicas. Nos APs, o miR-222 foi detectado em 22 amostras, sendo 31,8% com baixa expressão, 31,8% com expressão normal e 36,4% com expressão aumentada. Conclusão: Apesar de a proteína c-Kit ser expressa em ambas as neoplasias ­ AP e CAC, sua influência sobre as vias de sinalização MAPK e PI3K/AKT/mTOR ainda permanece por ser estabelecida. Ainda, os microRNAs 221 e 222 não mostram correlação consistente com a expressão de c-Kit nos tipos tumorais estudados.

Introduction: Salivary gland tumors present broad histological spectrum resulting from multiple tumor cell differentiation. Pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) are the commonest benign and malignant salivary gland neoplasms originated from the intercalated duct region, respectively, and are composed by luminal structures and myoepithelial cells. In a previous study we detected that protein c-kit is involved in the process of salivary gland morphogenesis and PA. c-Kit protein is important during embryogenesis, including gametogenesis, melanogeneis and hematopoiesis as well as in tumorigenesis. Its activation induces various intracellular responses through pathways such as MAPK and PI3K/AKT/mTOR signaling cascades. In salivary gland neoplasms, only a few reports have shown that alterations in KIT gene are present and proteins related to its signaling pathway as well as its post-transcriptional regulation. This study has aimed at evaluating in PA and ACC: (a) the proteins location of PI3K/AKT/mTOR and MAPK pathways using immunohistochemistry (IHC); (b) expression of miR-221 and miR-222, related to KIT gene; and (c) the association of these findings with clinical, pathological and survival data of patients. Results: In PA c-kit was positive in isolated luminal cells; in ACC, neoplastic luminal structures were positive for c-Kit. In PA, PI3K beta protein was shown to be partially positive in the cytoplasm of cells near the tumor capsule and phosphor AKT and phospho mTOR, are specifically expressed in epithelial cells and in a few myoepithelial. In ACC, PI3K and phosphor AKT protein showed to be negative in most of cases. Phospho mTOR protein was expressed in the cytoplasm of epithelial cells and some myoepithelial cells. In MAPK pathway, Ras, ERK1/2 and phosphor MEK-1 proteins were negative in most PAs and CACs; B-Raf and phospho MEK-2 were detected in luminal cells of PA. In ACC neoplastic luminal structures were positive for phospho MEK-2; B-Raf was also positive in myoepithelial and epithelial cells. In addition, cases with expressed phospho-mTOR and phosphor MEK-2 proteins were significantly associated with higher cancer-specific survival (p = 0.040 and p = 0.005, respectively). Moreover, expression of miR-221 was detected in 13 CAC samples and 19 PA samples. In CAC, expression of miR-221 was downregulated in 30,77% of the samples, upregulated in 30,77% samples, and normal in 38,46% samples. In PA, miR-221 expression was downregulated in 36,84% samples, upregulated in 10,53% samples, and normal in 52,63% samples. Expression of miR-222 was detected in 14 CAC samples and 22 PA samples. In the majority of CAC samples, the expression of miR-222 was similar to that observed in non-neoplastic samples. In PA samples, expression of miR-222 was downregulated in 31,8% samples, upregulated in 36,4% samples, and normal in 31,8% samples. Conclusion: Although c-Kit expression is detected in PA and ACC, its influence on the MAPK e PI3K/AKT/mTOR signaling cascades remains to be established. miR-221 e -222 did not show a robust correlation with c-Kit expression in the tumors studied.

A Case of Disseminated Intra-abdominal Gastrointestinal Stromal Tumor Managed with Low Dose Imatinib / 대한소화기학회지

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Imatinib mesylate is recommended as adjuvant therapy for GIST after surgical resection. However, drug-related adverse events are common. A 74-year-old female with metastatic GIST who was managed with imatinib experienced severe adverse events, including skin rashes, tremor, and alopecia, etc. The imatinib dose was reduced and the size of the metastatic GIST continued to decrease and adverse events showed significant improvement.

Massive Upper Gastrointestinal Bleeding from Multiple Gastrointestinal Stromal Tumor in a Neurofibromatosis Patient / 대한소화기학회지

No abstract available.

Vascular endothelial growth factor and KIT expression in relation with microvascular density and tumor grade in supratentorial astrocytic tumors

PURPOSE: To evaluate the relationship between microvascular density and the expression of vascular endothelial growth factor (VEGF) and KIT as possible markers of angiogenic stimulus in astrocytic tumors and correlate it with histopathological grading. METHODS: We enrolled 99 surgical specimens of supratentorial astrocytic tumors for analysis of VEGF and KIT and subsequent correlation with MVD and grading. RESULTS: KIT and VEGF expression correlated with microvascular density (p<0.005) and both VEGF and microvascular density correlated with grading (p<0.005). KIT had no significant relationship with grading (p=0.657). CONCLUSION: KIT and VEGF constitute important pathways in the angiogenesis of astrocytomas and therefore are promising prognostic tools and options for therapeutic intervention.

Primary extragastrointestinal stromal tumors: A clinicopathological and immunohistochemical study-A tertiary care center experience.

Background: Extra gastrointestinal stromal tumors (EGIST) are uncommon compared to their gastrointestinal counterparts. EGISTs involve omentum, mesentery, retroperitoneum, pancreas, and pelvis. Materials and Methods: Ten EGISTs were analyzed in this study from January 1995 to November 2011. They were analyzed with respect to clinical features, imageological, histopathological, and immunohistochemical findings. The immunohistochemical stains used were Smooth muscle actin (SMA), Desmin, S-100 protein, CD34 and CD-117. Results: There was slight female preponderance with wide age range. Four of the tumors were in retroperitoneum, three in mesentery, and two in omentum and one in pelvis. Histopathologically majority were spindle cell tumors. Immunohistochemically CD117 was consistently positive followed by CD34. Smooth muscle actin was positive in eight cases, S-100 protein and desmin were positive in two cases each. Conclusion: EGISTs are rare and should be considered in the differential diagnosis of the mesenchymal tumors and immunohistochemistry helps to confirm the diagnosis. Further study with better follow-up is desired to characterize these uncommon tumors.

Glyceollins, a novel class of soybean phytoalexins, inhibit SCF-induced melanogenesis through attenuation of SCF/c-kit downstream signaling pathways

The anti-melanogenesis effect of glyceollins was examined by melanin synthesis, tyrosinase activity assay in zebrafish embryos and in B16F10 melanoma cells. When developing zebrafish embryos were treated with glyceollins, pigmentation of the embryos, melanin synthesis and tyrosinase activity were all decreased compared with control zebrafish embryos. In situ expression of a pigment cell-specific gene, Sox10, was dramatically decreased by glyceollin treatment in the neural tubes of the trunk region of the embryos. Stem cell factor (SCF)/c-kit signaling pathways as well as expression of microphthalmia-associated transcription factor (MITF) were determined by western blot analysis. Glyceollins inhibited melanin synthesis, as well as the expression and activity of tyrosinase induced by SCF, in a dose-dependent manner in B16F10 melanoma cells. Pretreatment of B16F10 cells with glyceollins dose-dependently inhibited SCF-induced c-kit and Akt phosphorylation. Glyceollins significantly impaired the expression and activity of MITF. An additional inhibitory function of glyceollins was to effectively downregulate intracellular cyclic AMP levels stimulated by SCF in B16F10 cells. Glyceollins have a depigmentation/whitening activity in vitro and in vivo, and that this effect may be due to the inhibition of SCF-induced c-kit and tyrosinase activity through the blockade of downstream signaling pathway.

Características genético-moleculares de los tumores estromales gastrointestinales (GIST) / Molecular and genetic features of gastrointestinal stromal tumors (GIST)

Los tumores estromales gastrointestinales (GIST) son neoplasias mesenquimales que típicamente surgen a nivel del estómago, intestino delgado, colon, y otros sitios en la cavidad abdominal y su identificación se ha incrementado por mejoras en los criterios de detección. La mayor parte de los tumores GIST son causados por mutaciones activadoras en los genes de receptores transmembranares tirosina quinasa c-KIT y receptor alpha del factor de crecimiento derivado de plaquetas (PDGFRA). Las mutaciones causales de GIST se restringen solo a ciertas regiones del gen que corresponden a importantes zonas funcionales de c-KIT o PDGFRA. Se reporta que hasta 70% de casos de GIST se debe a mutaciones en el exón 11 del gen c-Kit que corresponde a la región yuxtamembrana del receptor. La región y el tipo de mutación determinan diferencialmente cómo se desarrolla la neoplasia, el pronóstico y su respuesta a inhibidores de las tirosina quinasas como el Imanatib. Por tal motivo, el genotipado de KIT y PDGFRA es importante para el diagnóstico y establecimiento de la sensibilidad a los inhibidores tirosina quinasa.

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms typically arising in the stomach, small intestine, colon, and other sites in the abdominal cavity and its identification has improved dramatically mainly due to better criteria in its detection. Most GISTs tumors harbor activating mutations in the tyrosine kinase receptor c-KIT or platelet derived growth factor receptor-alpha (PDGFRA). Those mutations are restricted to a few regions corresponding to important functional domains of c-KIT or PDGFRA. Upto 70% of cases are due to mutations in exon 11 of c-KIT corresponding to its juxtamembrane region of the receptor. The location and type of mutation will differentially determine the development of the disease, its prognosis and the response to inhibitors of tyrosine kinases as Imanatib. For this reason, genotyping c-KIT and PDGFRA is important for GIST diagnosis and assessment of sensitivity to tyrosine kinase inhibitors.

Immunophenotypes of Glycogen Rich Clear Cell Carcinoma

PURPOSE: Glycogen rich clear cell carcinoma (GRCC) of the breast is a rare subtype of invasive ductal carcinoma and involves a poor prognosis. In the literature, less than 150 cases have been reported. Many researchers have attempted to characterize GRCC according to electron microscope, flow cytometry, or clinical data. However, an organized study of the immunophenotype of GRCC has yet to be reported. MATERIALS AND METHODS: Here, we present three cases of GRCC and their immunohistochemical profiles. RESULTS: Histologically, all three cases contained periodic acid stain (PAS) positive and d-PAS labile granules in their clear cytoplasm. Case I showed positivity for only estrogen receptor (ER) and c-erbB2. Case II exhibited positivity for progesterone receptor and negativity for ER and c-erbB2. Case III presented with triple negative invasive carcinoma. The expression pattern of E-cadherin was concordant with epidermal growth factor receptor and c-kit, but discordant with ki-67. Among these three cases, p53-positive cases exhibited a low proliferative index (ki-67: 15%), while p53-negative cases showed a high proliferative index (ki-67: 50-60%). CONCLUSION: In conclusion, the immunophenotype of GRCC is not uniform, but is similar to that of conventional ductal carcinoma.

Clinicopathologic spectrum of gastro intestinal stromal tumours - Experience at a tertiary care center.

Context: Accurate diagnosis of Gastrointestinal stromal tumors (GISTs) and categorization of risk groups is crucial in the wake of targeted drug therapy. Aim: This study was undertaken to obtain insight into the clinicopathologic features of GISTs. Materials and Methods: Retrospective study of 20 cases of c-KIT (CD 117) positive GISTs .Various histologic parameters were studied. Immunohistochemical panel included CD-34, Smooth muscle actin, S-100, Desmin, and Vimentin. Risk categorization was done as per standard protocol. Clinical details and follow up were retrieved from cases files. Results: Of the total 20 cases, 15 were males. The mean age of presentation was 52 years. 50 % of the cases presented with gastro intestinal bleeding .The cases were categorized as high risk (60%), intermediate risk (20%), low risk (15%) and very low risk (5%). Stomach and small intestine were commonly involved and in 6 of the cases there were metastatic nodules in the mesentery/omentum/ peritoneum. Spindle cell morphology was the commonest histological pattern (55%). Nuclear pleomorphism, perivascular whorling, mucosal and fat invasion were seen only in the high risk group. CD-34, SMA and S-100 were positive in 90%, 30%, and 10% of the cases, respectively, with consistent Desmin negativity. Conclusions: Cases of GISTs in our clinical setting presented a decade earlier and mostly belonged to the high risk group. Certain histological features such as necrosis, and perivascular whorling were more commonly associated with the high risk groups.

Clinicopathologic Study on Combined Hepatocellular Carcinoma and Cholangiocarcinoma: with Emphasis on the Intermediate Cell Morphology

Combined hepatocellular carcinoma and cholangiocarcinoma (combined HCC-CC) is a rare subtype of primary liver cancer. We investigated the histopathologic features of transitional or intermediate areas in 21 combined HCC-CCs and immunophenotypes using different hepatic progenitor cell markers (CK7, CK19, c-kit, NCAM, and EpCAM). Major histologic findings of transitional or intermediate areas of 21 combined HCC-CCs included strands/trabeculae of small, uniform, oval-shaped cells with scant cytoplasm and hyperchromatic nuclei embedded within an abundant stroma, small cells with an antler-like anastomosing pattern, and solid nests of intermediate hepatocyte-like cells surrounded by small cells in periphery, in order of frequency. The intermediate area of one tumor was composed predominantly of spindle cells arranged in short fascicles. Immunophenotype of tumor cells with intermediate morphology suggested a progenitor cell origin for this tumor. Clinical findings of combined HCC-CC showed a closer resemblance with those of HCC than those of CC. In univariate analysis, tumor size, TNM stage, and serum alpha-fetoprotein levels showed a significant association with poor patient survival. Serum alpha-fetoprotein level was an independent prognostic indicator in multivariate analysis. In conclusion, an awareness of the clinicopathologic features, specifically the various morphologic features of intermediate areas in this tumor, is essential for prevention of potential misdiagnosis as another tumor.

Carcinoma ex Pleomorphic Adenoma of the Salivary Glands: Distinct Clinicopathologic Features and Immunoprofiles Between Subgroups According to Cellular Differentiation

In carcinoma ex pleomorphic adenoma (CXPA), pleomorphic adenoma (PA) and diverse carcinoma components showing luminal (ductal) or non-luminal (myoepithelial) differentiation coexist. To elucidate the clinicopathological implications of cellular differentiation in CXPA and the potential role of p53, vascular endothelial growth factor (VEGF), c-erbB-2, c-kit, and glucose transporter 1 (Glut-1) in carcinogenesis, we analyzed 11 CXPAs with luminal differentiation (CXPAs-LD) and 6 CXPAs with non-luminal differentiation (CXPAs-NLD) and compared protein expressions in residual PAs and carcinomas by immunohistochemistry. Among the CXPAs-LD, 5 were invasive and 8 were histologically high-grade tumors. The 5-year survival rate was 72.7%. P53, c-erbB-2, VEGF, and Glut-1 were more immunoreactive in carcinoma components than in PAs (P = 0.008, 0.004, 0.002, and 0.024, respectively); c-erbB-2 overexpression was associated with high histological grade (P = 0.024). Carcinoma components frequently lacked c-kit expression (P = 0.009). CXPAs-NLD were all low-grade and invasive with a larger mean tumor size (5.2 cm) than CXPAs-LD (3.3 cm) (P = 0.040). The patients remained disease-free without significant immunohistochemical expression. The immunoprofiles and clinical course of CXPA differed according to cellular differentiation. Therefore, it is important to report the histological subtype and to assess potential biomarkers in diagnostic and therapeutic trials.

Clinicopathlogic and Immunohistochemical Characteristics of Triple Negative Invasive Lobular Carcinoma

PURPOSE: Our study is performed to find out clinicopathlogic and immunohistochemical (IHC) characteristics of triple negative invasive lobular carcinoma (ILC), as has been demonstrated in their invasive ductal counterparts. MATERIALS AND METHODS: Retrospective analysis of variable clinicopathlogic parameters and IHC stains for androgen receptor, estrogen receptor, progesterone receptor, p53, c-kit, galectin-3, cytokeratin 5 (CK5), CK5/6, vimentin, E-cadherin, epidermal growth factor receptor, and HER2 were performed in 117 cases of ILC. RESULTS: Eight cases (6.8%) were triple negative carcinoma (TNC), which showed higher incidence of high histologic grade than non-TNC (p = 0.019). Galectin-3 was expressed with higher incidence in tumor cells of TNC (62.5%) than those of non-TNC (7.3%) (p = 0.000). In contrast, galectin-3 was expressed with higher incidence in stromal cells of non-TNC (53.2%) than those of TNC (12.5%) (p = 0.029). CK5 and CK5/6 were not expressed in all ILCs. CONCLUSION: TNC in ILC showed distinct clinicopathologic and IHC characteristics such as higher histologic grade and increased expression of galectin-3, compared to non-TNC in ILC. TNC in ILC was less frequent and did not show CK5 and CK5/6 expression when compared to TNC in invasive ductal carcinoma.

Expresión inmunohistoquímica de vimentina, CD 34 y c-Kit (CD 117) en tumores estromales gastrointestinales (GISTs) / Inmunohistochemistry expression of vimentin, CD 34 and c-Kit (CD117) in gastrointestinal stromal tumors

Los tumores estromales gastrointestinales (GISTs) comprenden a tumores de origen mesenquimal que antes eran clasificados como "tumores del músculo liso", no obstante los avances en el campo de la microscopía electrónica e inmunohistoquímica han permitido su diferenciación. Derivan de las células intersticiales de Cajal, representan el 1-2 por ciento de todas las neoplasias del tubo digestivo y son más frecuentes en personas mayores de 40 años, con igual incidencia en ambos sexos. Se estudiaron 30 casos de GISTs en un análisis prospectivo y retrospectivo, en el período comprendido entre los años 1987 y 2007. Para el material retrospectivo se estudiaron bloques de tejidos en parafina. El material se fijó en formaldehído al 10 por ciento y se incluyó en parafina, realizando tinciones habituales con H&E y técnicas histoquímicas (P.A.S y tricrómico de Masson). Se realizó, además, panel inmunohistoquímico: Vimentina, Actina de músculo liso, CD-34 y c-Kit (CD-117). Con el fin de estudiar las características anatomopatológicas, en relación a la sintomatología clínica que presentan los GISTs, se observó el comportamiento de los mismos teniendo en cuenta diferentes variables. Con respecto a la inmunohistoquímica, la vimentina fue positiva en el 100 por ciento de los casos, mientras que CD-34 y CD-117 fueron positivos en aproximadamente el 90 por ciento. La tendencia de estos tumores a seguir un curso clínico impredecible, con riesgo de recidiva tardía y de metástasis, hace recomendable el seguimiento del paciente regularmente y por un período indefinido. El haber tenido la oportunidad de estudiar 30 pacientes portadores de GISTs mediante la implementación de técnicas inmunohistoquímicas, a los fines de confirmar la histogénesis tumoral, motivan la presente comunicación.

GIST’s are tumors of mesenchymal origin that were previously classified as smooth muscle tumors despite the advances in the field of electron microscopy and immunohistochemistry have allowed their differentiation. They derive from interstitial cells of Cajal. They account for 1-2 percent of all cancers of the digestive tract. They are more common in people over 40 years of age, with equal incidence in both sexes. We studied 30 cases of gastrointestinal stromal tumors in a prospective and retrospective analysis in the period between 1987 and 2007. For retrospective material were studied in paraffin tissue blocks. They were fixed in formaldehyde to 10 percent and included in paraffin by routine staining with H&E and histochemical techniques (PAS and Masson trichrome). We performed further, immunohistochemical de panel: Vimentin, smooth muscle actin, CD-34 and c-Kit (CD-117). To study the pathological features in relation to the clinical symptoms presented by GIST’s, we observed the behavior of the same taking into account different variables. With regard to immunohistochemistry, vimentin was positive in 100 percent of the cases, whereas CD-34 and CD-117 were positive in approximately 90 percent. The tendency of these tumors follow an indolent clinical course with late recurrence risk, does recommend monitoring patients regularly and for an indefinite period. The rarity of this disease, having had the opportunity to study 30 cases of GISTs and analysis of the value of immunohistochemistry for the confirmation of the histogenesis object of the present communication.

A Case of Primary Extragastrointestinal Stromal Tumor Presenting as Peritoneal Dissemination / 대한소화기학회지

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract, but also occurs at a lower frequency in extra-gastrointestinal regions such as omentum, mesentery, retroperitoneum and undefined abdominal sites. This tumor is called extragastrointestinal stromal tumor (EGIST). EGIST is mostly diagnosed as a cystic mass, but rarely occurs as a disseminated abdominal tumor. We experienced a 70-year-old man with primary EGIST presenting as peritoneal dissemination. Abdominal CT showed diffuse peritoneal thickening with a large amount of ascites, but no definite mass lesion. Laparoscopic biopsy was performed and histologic findings showed tumor composed of epithelioid cells. In the results of immunohistochemical stains, the tumor showed positive reactivity with CD117 (c-kit), CD34, vimentin and actin, but negative reactivity with desmin and S-100 protein. On account of unresectability and histologic parameters of malignant behavior, he was started on imatinib.

Clinical Practice Guideline for Accurate Diagnosis and Effective Treatment of Gastrointestinal Stromal Tumor in Korea

Despite the rarity in incidence and prevalence, gastrointestinal stromal tumor (GIST) has emerged as a distinct pathogenetic entity. And the clinical management of GIST has been evolving very rapidly due to the recent recognition of its oncogenic signal transduction pathway and the introduction of new molecular-targeted therapy. Successful management of GIST requires a multidisciplinary approach firmly based on accurate histopathologic diagnosis. However, there was no standardized guideline for the management of Korean GIST patients. In 2007, the Korean GIST study group (KGSG) published the first guideline for optimal diagnosis and treatment of GIST in Korea. As the second version of the guideline, we herein have updated recent clinical recommendations and reflected changes in diagnosis, surgical and medical treatments for more optimal clinical practice for GIST in Korea. We hope the guideline can be of help in enhancing the quality of diagnosis by members of the Korean associate of physicians involving in GIST patients's care and subsequently in achieving optimal efficacy of treatment.

Ca2+-activated K+ Current in Freshly Isolated c-Kit Positive Cells in Guinea-pig Stomach

This study was designed to isolate Ca2+-activated K+ current (IKCa) and elucidate its physiological significance in freshly isolated interstitial cells of Cajal (ICCs) of guinea-pig stomach. Single ICC was freshly isolated by enzymatically dissociating from myenteric border of gastric antrum free of circular muscles, and conventional whole-cell voltage clamp technique including immunohistochemical techniques were employed to characterize the cells: In myenteric border of gastric antrum, ICC-MY (ICCs from myenteric border) were detected by immunohistochemical reactivity, and single ICC-MY which has many branches was immunohistochemically c-Kit positive. Under K+-rich and 0.1 mM ethylene glycol-bis (2-aminoethyl ether)-N,N,N',N'-tetraacetic acid pipette solution, ICC produced spontaneous inward current (-256+/-92.2 pA). When step-depolarizing pulse from -80 to +80 mV was applied at holding potential (Vh) of -80 mV, voltage-dependent outward currents were recorded with superimposed spontaneous transient outward currents (STOCs). Both STOCs and outward currents were reversibly affected by tetraethylammonium chloride (TEA) and iberiotoxin (IbTX); 2 mM TEA and 200 nM IbTX completely abolished STOCs and significantly inhibited outward K+ current over the whole potential range tested for current/voltage (I/V) relationship. In addition, TEA delayed repolarization phase of spontaneous inward current. The present results indicate the presence of IKCa in a single ICC, and it might be involved in regulation of repolarizing phase of spontaneous inward current in guinea-pig stomach.

Tumores del estroma gastrointestinal (GIST): revisión de la literatura / Gastrointestinal stromal tumors (gist): literature review

Los tumores del estroma gastrointestinal representan un tipo infrecuente de tumor de origen mesenquimático, con origen en las células intersticiales de Cajal. Se caracterizan por expresar un receptor de membrana mutante con actividad tirosina quinasa anormal (c-kit CD117) que condiciona su activación permanente y una proliferación celular no controlada. Pueden encontrarse a cualquier nivel del tracto gastrointestinal, pero son más frecuentes en estómago e intestino delgado. Frecuentemente cursan de forma asintomática, constituyendo un hallazgo endoscópico o radiológico. La enfermedad localizada habitualmente es de buen pronóstico tras su resección quirúrgica, mientras que la sobrevida es baja en etapas avanzadas, con escasa respuesta a la quimioterapia convencional. El surgimiento del imatinib, un inhibidor de la tirosina quinasa, ha representado un verdadero hito, dado su eficacia en el control de la enfermedad irresecable o metastásica, permitiendo un importante aumento en la sobrevida de estos pacientes.

Gastrointestinal Stromal Tumors in Koreans: It's Incidence and the Clinical, Pathologic and Immunohistochemical Findings

Seven hundred forty seven cases of gastrointestinal stromal tumors (GISTs) in Koreans who were diagnosed between 2001 and 2002 were analyzed to evaluate their occurrence and their clinical, pathologic and immunohistochemical findings. The most frequent location of tumor was in the stomach (63%), followed by the small intestine (30%), the colorectum (5%), and the esophagus (2%). c-kit expression was found in 93.6% of the cases, while CD34, SMA and S-100 protein was positive in 80.1%, 28.2%, and 20.2%, respectively. c-kit positivity was high in the stomach (94.2%) and small intestine (94.6%), while it was relatively low in the colorectum (85.0%), and esophagus (81.2%). The positivity for CD34 was correlated with the higher risk of GISTs (p=0.04). Follow up of the patients showed that 58 primary GISTs patients died and 20 of these patients were recurrent or metastatic at the time of diagnosis. The pathologic diagnosis to predict the risk of aggressive behavior of GISTs was correlated with the numbers of tumor, clinical stage, epithelioid histologic type, cellularity, cellular atypia, necrosis, and mucosal invasion (p= 0.00). GISTs with a poor prognosis were closely related to the clinical stage at presentation, the locations of the tumor, and the ages of the patients.