Mast cells in oral lichen planus and oral lichenoid lesions related to dental amalgam contact

Abstract The aim of this study was to analyze the expression of mast cell markers toluidine blue, c-kit, and tryptase and presence of mononuclear inflammatory cells in oral lichen planus (OLP) and oral lichenoid lesions related to dental amalgam. Nineteen specimens of OLP, OLLC, and healthy oral mucosa were selected. Mononuclear inflammatory cells were analyzed. Histochemical and immunohistochemical analyses were performed using toluidine blue, anti-c-kit and anti-tryptase reagents, and the results were quantified in areas A and B of connective tissue. Mast cells of all OLP and OLLC samples were positive for toluidine blue, c-kit, and tryptase. The density of toluidine blue+, c-kit+ and tryptase+ mast cells was higher in tissue with OLP and OLLC compared with healthy controls (p < 0.05). No difference was noted in mast cells density between OLP and OLLC (p > 0.05). The density of tryptase+ mast cells was higher in the subepithelial region (area A) than the region below it (Area B) in OLLC (p = 0.047). The mononuclear inflammatory cell density was higher in OLLC compared to OLP, but without statistical significance (p > 0.05). A positive statistical correlation was found between mononuclear immune cells and density of c-kit+ and tryptase+ mast cells in OLP (r = 0.943 and r = 0.886, respectively). Our data demonstrate that the etiopathogenesis process of OLP and OLLC modulates the expansion and degranulation of mast cells; mast cells density, however, was similar between OLP and OLLC. The distribution of mast cells appears to vary along the lamina propria.

Interferon, interleukin 2 combined with lenalidomide for elderly acute myeloid leukemia with minimal residual disease-positive: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the effect of interferon, interleukin 2 (IL-2) combined with lenalidomide in the treatment of acute myeloid leukemia (AML) with minimal residual disease (MRD)-positive.Methods:The clinical data of 1 elderly AML patient with persistent MRD positive treated with interferon, IL-2 combined with lenalidomide in the Affiliated Cancer Hospital of Zhengzhou University in December 2019 were retrospectively analyzed, and the relevant literature was reviewed.Results:The 72-year-old male patient was diagnosed as AML-M 2b with c-kit mutation, the low-risk group according to laboratory related examinations, flow cytometry, genetic testing. The patient did not achieve remission after 1 cycle of standard VA (venetoclax + azacitidine) regimen, and achieved complete remission (CR) after another 1 cycle of IA (idarubicin + cytarabine) induction regimen, followed by consolidation therapy with medium dosage cytarabine and D-CAG (decitabine + cytarabine + aclarubicin + granulocyte colony-stimulating factor) regimen, during which the AML1-ETO fusion gene progressively increased. After programmed death receptor 1 (PD-1) inhibitor-based combination therapy, the AML1-ETO fusion gene remained negative for more than 1 month, and then increased again; subsequently, the patient was treated with the ITI (interferon, thalidomide, and interleukin-2) regimen, and the AML1-ETO fusion gene remained negative for more than 7 months; thalidomide was changed to lenalidomide after the increase again, and AML1-ETO fusion gene remained negative again for 2 years until May 2023. Conclusions:Interferon, IL-2 combined with lenalidomide have a significant therapeutic efficacy in reversing MRD positive and have mild adverse reactions, which can be used as a new option for refractory AML.

Effect of C-KIT gene mutation on the prognosis of acute myeloid leukemia associated with core-binding factor in children: a Meta-analysis / 白血病·淋巴瘤

Objective:To systematically evaluate the relationship between C-KIT gene mutation and the prognosis of childhood core-binding factor-related acute myeloid leukemia (CBF-AML).Methods:The PubMed database was searched with "KIT" "Acute Myeloid Leukemia" and "Children"; the Chinese Journal Full-text Database (CNKI), Chinese Biomedical Literature Database (CBM), VIP database and Wanfang database were also searched with "KIT" "Acute Myeloid Leukemia" and "Children", and the search time was from the establishment of the database to October 1, 2020. After strict screening, the literature was included in the analysis; according to the presence or absence of genetic changes, the included cases was divided into C-KIT mutation group and wild group, and the complete remission (CR) rate, event-free survival (EFS) rate, and overall survival (OS) rate of the two groups were analyzed.Results:Six articles were collected, including 4 articles in English and 2 articles in Chinese, with a total of 667 patients. There was a statistically significant difference in the EFS rate between the C-KIT mutation group and wild group in children with CBF-AML ( HR = 2.40, 95% CI 1.47-3.89, P = 0.001); there was no significant difference in the CR rate and OS rate ( OR = 0.93, 95% CI 0.48-1.80, P = 0.830; HR = 1.92, 95% CI 0.96-3.83, P = 0.065) between the two groups. Conclusions:C-KIT gene mutation may be a risk factor for poor prognosis in children with CBF-AML.

A comparison between cDNA and DNA samples for the detection of c-KIT exon 17 mutation in acute myeloid leukemia patients / 中华检验医学杂志

Objective To investigate the impact of sample typeon the detection of c-KIT exon 17 mutation in acute myeloid leukemia (AML) patients. Methods A retrospective study was conducted on 51 bone marrow samples collected from 37 AML patients [17 maleand 20 female, with a median age of 33 (range from 1 to 82)] at diagnosis or after treatment from June 2016 to August 2018. Of the 37 cases of AML, 24 were t(8; 21) AML, 11 were inv(16)/t(16;16) AML and 2 were non-CBF-AML. RNA and DNA were simultaneously extracted from every sample. PCR followed by Sanger sequencing were used to screen c-KIT exon 17 mutation, and the comparisons were made between paired cDNA and DNAsamples. Results (1) Of the 51 paired samples, 14 pairs were simultaneously detected positive for c-KITmutation in both of cDNA and DNA samples, but 17 pairs were detected negative in both, and the remaining 20 pairswere only detected positive for the mutation in cDNA but not in DNA, with an inconsistency rate of 39.2％. The positive rate of detecting c-KITmutation was significantly higher in cDNA than in DNA samples (66.7％vs 27.5％,P=0.000073). (2)Inconsistent mutation results between paired cDNA and DNA samples occurred in t(8;21)AML, inv(16)AML and non-CBF-AML patients with the inconsistency rate of 36.4％(12/33), 27.2％(3/11) and 71.4％ (5/7), respectively. (3)The inconsistency rate was significantly higher in samples collected after treatment compared with those collected at diagnosis (72.7％vs 13.8％, P=0.00003). (4) All 5 serially monitored patients with c-KITmutation had inconsistency in mutation detection between cDNA and DNA samples during follow up. Conclusion cDNA improves the detection of c-KIT exon 17 mutation in AML patients compared with DNA, which is especially common after treatment.

No detection of c-kit gene mutations in exons 9, 11, 13 and 17 and low CD117 expression in plaque-stage mycosis fungoides

Abstract: The growth factor receptor c-kit (CD117) is expressed in immature T-cells and in some advanced forms of mycosis fungoides. c-kit gene mutation results in unrestricted neoplastic proliferation. We aimed to detect by PCR the most frequent exon mutations in seventeen plaque-stage MF patients, in their perilesional skin and in healthy skin donors. We secondarily evaluated CD117 expression by immunohistochemistry in plaque-stage and tumor-stage MF. We detected no mutation in c-kit gene and low CD117 expression was confirmed on atypical cells in one patient. Complete c-kit exon and intron sequences should be assessed and more sensitive sequencing method could be also applied.

Evaluation of the relationship between c-Kit expression and mean platelet volume in classic Kaposi's sarcoma

Abstract: Background: c-Kit is a proto-oncogene that encodes tyrosine kinase receptor (CD117). Mean platelet volume (MPV) is a useful marker, providing information on platelet function and diameter. Objective: To investigate c-Kit expression and intensity in patients with Kaposi's sarcoma (KS) and to investigate the relation between Ki-67 proliferation and MPV. Methods: A total of 32 patients, diagnosed with classic cutaneous KS, were included in this study. We reevaluated the histopathological reports with the preparations, confirmed the diagnosis and then determined the patients' histopathological stages. c-Kit expression and Ki-67 proliferation were investigated immunohistochemically in KS cases, while MPV in all cases was checked. Results: Although c-Kit expression was detected in 22 cases (68.8%), it was not expressed in 10 cases (31.2%). We detected 8 cases with + (25%), 6 with ++ (18.8%) and 8 with +++ (25%). Ki-67 expression was 5.0% (min-max 1.0-20.0). Relapse was observed in 5 cases (15.6%) out of 32. There was positive correlation between c-Kit expression and MPV (rs=0.598, p<0.001), and between c-Kit intensity and MPV (rs=0.588, p<0.001). Conclusion: c-Kit is highly positive in KS. c-Kit positivity indicates a high risk of tumor growth, invasion and relapse. Furthermore, c-Kit expression stimulates megakaryocytes to release young and large thrombocytes into the periphery. Thus, high MPV, c-Kit expression and immunostaining intensity indicate high invasion and relapse in KS subjects.

Effect of curcumin on the activity and migration of as well as c-kit mRNA expression in melanocytes / 中华皮肤科杂志

Objective To explore the effect of curcumin on the activity and migration of as well as c-kit mRNA expression in melanocytes.Methods Human epidermal melanocytes were isolated from the prepuce in adolescents and subjected to primary culture.To estimate the effect of curcumin on the proliferative activity of melanocytes, some melanocytes were randomly divided into several groups to be cultured in the MelM-2 medium with or without the presence of 5, 10, 20 or 30 μmol/L curcumin, the MelM-2 medium containing curcumin of 5-30 μmol/L served as the drug control groups, and the MelM-2 medium without curcumin served as the blank control group.After 24 and 48 hours of culture, MTS assay was performed to evaluate the proliferative activity of melanocytes.Some cultured melanocytes were randomly divided into 4 groups to be cultured in the MelM-2 medium with 0, 5, 10 and 20 μmol/L curcumin respectively for 48hours.Then, wound scratch assay was conducted to estimate the migratory activity of melanocytes, and real-time fluorescence-based quantitative PCR to quantify the mRNA expression of c-kit in melanocytes.Statistical analysis was carried out by factorial design analysis of variance (ANOVA), one-way ANOVA and least significant difference (LSD)-t test.Results The proliferative activity of melanocytes was significantly decreased at 24 and 48 hours in the 30-μmol/L curcumin group compared with the negative control group (0.783 ± 0.053 vs.1.000 ± 0.018 at 24 hours, 0.637 ± 0.015 vs.0.993 ± 0.064 at 48 hours, both P ＜ 0.05), while no significant differences were observed between the other curcumin groups and the negative control group (all P ＞ 0.05).The 48-hour treatment with curcumin could significantly inhibit the migration of melanocytes in the 5-, 10-and 20-μmol/L curcumin groups compared with the control group (all P ＜ 0.05).The mRNA expression level of c-kit was also significantly reduced at 48 hours in the 5-, 10-and 20-μmol/L curcumin groups compared with the control group (1.799 ± 0.372, 1.539 ± 0.224 and 1.026 ± 0.038 vs.3.371 ± 0.352, all P ＜0.05).Conclusion Curcumin at low concentrations (≤ 20 μmol/L) has no obvious cytotoxicity against melanocytes, but can inhibit the migration of and c-kit mRNA expression in melanocytes, while curcumin at 30 μmol/L can promote the apoptosis of melanocytes.

Effect of ferulic acid on the proliferation of, as well as melanin synthesis, tyrosinase activity and expressions of c-kit and ERK proteins in keratinocytes / 中华皮肤科杂志

Objective To evaluate the in vitro effect of ferulic acid on the proliferation of,as well as melanin synthesis,tyrosinase activity and expressions of c-kit and ERK proteins in cultured normal human epidermal melanocytes.Methods Cultured normal human epidermal melanocytes were treated with various concentrations of ferulic acid for different durations,and those remaining untreated served as the control.Then,3-(4,5-dimethylthiazol2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium,inner salt (MTS) assay was performed to estimate cell proliferative activity at 24,48 and 72 hours,sodium hydroxide solubilization method to quantify melanin content in melanocytes at 72 hours,dopa oxidation assay to evaluate tyrosinase activity at 72 hours,Western blot to measure the expressions of c-kit and ERK1/2 proteins at 72 hours.Results Cellular proliferative activity was significantly inhibited in melanocytes treated with ferulic acid of 0.01,0.1 and 1 mg/ml for 24,48 and 72 hours compared with untreated melanocytes (all P ＜ 0.05),and the 72-hour treatment with ferulic acid of 1 mg/ml showed the strongest inhibitory effect.Ferulic acid at 0.01,0.1 and 1 mg/ml all markedly suppressed melanin synthesis and tyrosinase activity,decreased the expressions of c-kit and ERK1/2 proteins in melanocytes,with significant differences in these parameters between ferulic acid-treated and untreated melanocytes (all P ＜ 0.05).Conclusions Ferulic acid could downregulate the proliferation of,as well as melanin synthesis,tyrosinase activity,and expressions of c-kit and ERK proteins in cultured human epidermal melanocytes.

Expression of hypoxia-inducible factor-1α in acral malignant melanoma tissue / 中华皮肤科杂志

Objective To measure the expression of hypoxia-inducible factor (HIF)-1α in acral malignant melanoma (MM) tissue and to investigate its relationship with the stem cell factor (SCF)/c-kit pathway.Methods Immunohistochemical staining was performed to measure the expression of HIF-1α in tissue specimens from lesions of 93 patients with acral MM,21 with non-acral MM,39 with acral melanocytic nevi,and from the normal acral skin of 15 healthy human controls.Meanwhile,the expression of c-kit was detected by immunohistochemical staining in the 93 acral MM tissue specimens.Statistical comparisons were carried out by chi-square test and Mann-Whitney U test.The relationship of HIF-1α expression with c-kit expression as well as tumor progression and staging was assessed by Spearman correlation analysis.Results Immunohistochemistry showed that the expression rate of HIF-1α was 87.10％ (81/93) in acral MM specimens,90.48％ (19/21) in non-acral MM specimens,15.38％ (6/39) in acral melanocytic nevus specimens,but 0 (0/15) in the normal acral skin specimens.The expression of HIF-1α was significantly higher in acral MM lesions than in normal acral skin and acral melanocytic nevus lesions (both P ＜ 0.01),and significantly different between acral MM and non-acral MM lesions (P ＜ 0.01).Moreover,HIF-1α expression was positively correlated with Clark level and Breslow depth of melanoma (rs =0.442,0.368,respectively,both P ＜ 0.01),with the progression of acral MM (from in situ to aggressive and metastatic MM) (rs =0.420,P ＜ 0.01),and with the expression of c-kit (rs =0.307,P ＜ 0.01).Conclusions HIF-1α is highly expressed in acral MM,positively correlated with the staging,progression and aggression of MM,and co-expressed with c-kit in acral MM tissue,suggesting that both HIF-1α and c-kit take part in the pathogenesis of acral MM.

Preliminary recognition of stem cells surface markers in hepatoblastoma / 重庆医学

Objective To preliminarily screen the neoplastic stem cell (NSC) related surface markers combination and to under-stand the NSC distribution in hepatoblastoma(HB) .Methods The children cases of HB undergone the surgical therapy in the Jian-gxi Provincial Children′s Hospital were selected .The immunohistochemical method was adopted for observing the expression and distribution of NSC-related markers CD34 ,Thy-1 ,c-kit ,CD56 and stem cell factor(SCF) in the HB tissue and the normal hepatic tissue away from the edge of tumor tissue 3cm outside .Results Thy-1 and c-kit were sporadically distributed in the HB tissue and mainly focued on the portal area ,but did not exressed in the normal liver tissue ;the expression of CD34 and SCF in HB was signifi-cantly higher than that in the normal liver tissue(P0 .05) .Conclusion The different NSC related surface markers are distributed in the HB tissue and focus on the specific areas .The positive cells of Thy-1/c-kit expression may play a role in the HB occurrence .

Avaliação anatomoclínica e molecular do melanoma cutâneo em pacientes jovens (idade 18-30 anos) / Clinicopathologic and molecular evaluation of cutaneous melanoma in young patients (age 18-30)

A incidência do melanoma cutâneo em pacientes adultos jovens tem aumentado consideravelmente nos últimos anos. Há, contudo, carência de conhecimentos clinicopatológicos e moleculares sobre os melanomas que ocorrem nessa faixa etária. O presente estudo teve por objetivo avaliar 132 casos de melanoma cutâneo primário em pacientes com idade entre 18 e 30 anos, com ênfase no estudo das características clínicas, histopatológicas e avaliação molecular das mutações nos genes BRAF, NRAS e KIT. Em relação aos achados clínicos e histopatológicos, houve predomínio de indivíduos do sexo feminino (61,4%), sendo o tronco o sítio anatômico mais comumente envolvido (44,3%) e o melanoma extensivo superficial o tipo histológico predominante (79,5%). A mutação V600E no gene BRAF (BRAFV600E) foi analisada em 93 casos, utilizando-se a técnica de RT-PCR. Essa mutação foi identificada em 38,7% (36/93) e, estatisticamente, associada à fase vertical de crescimento (p = 0,01), infiltrado inflamatório discreto (p = 0,02) e presença de mitose intradérmica (p = 0,004). Houve, ainda, forte indício de associação com a presença de ulceração (p = 0,05). Todas essas variáveis apresentaram associação com pior prognóstico do melanoma cutâneo. Observou-se predomínio da mutação BRAFV600E em regiões anatômicas relacionadas à exposição solar intermitente. Nenhum caso de melanoma com fenômeno de regressão apresentou mutação BRAFV600E (p < 0,05). Não houve associação significativa entre BRAFV600E e sexo, tipo histológico, nível de Clark, índice de Breslow, elastose solar, invasão angiolinfática e perineural, satelitose, nevo melanocítico coexistente e sobrevida. A pesquisa de mutações NRAS, pela técnica de RT-PCR, detectou frequência de 3,95% (3/76). As três mutações encontradas foram do tipo 61K e ocorreram em pacientes do sexo masculino e em região de cabeça e pescoço. As mutações BRAFV600E e NRAS, quando presentes, eram mutuamente exclusivas. A frequência de mutações KIT, analisadas por...

The incidence of cutaneous melanoma in young adults has dramatically increased in recent years. However, there is scarce data about the clinicopathological and molecular characteristics on the melanomas occurring at this age group. The present study aimed to evaluate 132 patients aged between 18 and 30 years with primary cutaneous melanoma with emphasis on the study of clinical, histopathological characteristics and molecular evaluation of mutations in BRAF, NRAS and KIT genes. Regarding the clinical and histopathological findings, the following results were found: female predominance (61.4%), trunk was the most commonly anatomical site involved (44.3%) and superficial spreading melanoma, was the most common histological type (79.5 %). The V600E mutation in BRAF (BRAFV600E) gene was analyzed in 93 cases, using RT-PCR. It was present in 38.7% (36/93) and statistically related to the vertical growth phase (p = 0.01), mild inflammatory infiltration (p = 0.02) and the presence of intradermal mitosis (p = 0.004). There was, also, strongly evidence of an association with the presence of ulceration (p = 0.05). Worse prognosis was associated with these variables. There was a predominance of BRAFV600E mutation in anatomical regions related to intermittent sun exposure. No cases of melanoma with BRAFV600E mutation showed regression phenomenon (p < 0.05). There was no significant association between BRAFV600E and gender, histological type, Clark level, Breslow thickness, solar elastosis, angiolymphatic and perineural invasion, sattelitosis, coexisting melanocytic nevus and survival. The presence of a mutation in NRAS, by RT-PCR was seen in 3.95% (3/76) of the cases. All these three mutations were of type 61K, occurred in male patients and the head and neck region. BRAFV600E and NRAS mutations, when present, were mutually exclusive. The frequency of KIT mutations, analyzed by sequencing, was 11.1% (3/27). The three mutations identified in this gene were located in...

Effect of tacalcitol on the proliferation, adhesion, migration and c-kit mRNA expression of human epidermal melanocytes / 中华皮肤科杂志

Objective To evaluate the effect of tacalcitol on the proliferation,adhesion,migration and c-kit mRNA expression of cultured human epidermal melanocytes.Methods Cultured epidermal melanocytes from the prepuce of adolescent males were treated with various concentrations of tacalcitol.Then,cell proliferation was evaluated by tetrazolium salt (XTT) assay after 24,48 and 72 hours of treatment,adhesive activity by using fibronectin-coated culture plates after 72 hours,migratory activity by Transwell assay using a microporous membrane after 24 hours,and the c-kit mRNA expression was semiquantitatively analyzed by reverse transcription PCR after 72 hours of treatment.Statistical analysis was done by repeated-measure analysis of variance and completely random design analysis of variance.Results As repeated-measure analysis of variance showed,tacalcitol of 10-10,10-9,10-8,10-7 and 10-6 mol/L significantly promoted the proliferation of melanocytes (F =9.47,P ＜ 0.01),with significant differences in the promoting effect among various durations of treatment with different concentrations of tacalcitol (F =14.44,P ＜ 0.01),and with significant interaction effect between drug concentration and treatment duration (F =2.47,P ＜ 0.01).The highest proliferation level was observed in melanocytes treated with tacalcitol of 10-s mol/Lfor 72 hours.There was a significant increase in the adhesion rate of human epidermal melanocytes to fibronectin after treatment with tacalcitol of 10-8-10-7 mol/L for 72 hours (both P ＜ 0.01),number of melanocytes migrating through micropore membranes per high-power field (× 200) after treatment with tacalcitol of 10-9-10-8 mol/L for 24 hours (both P ＜ 0.01),and in the c-kit mRNA expression in melanocytes treated with tacalcitol of 10-9-10-7mol/L for 72 hours (all P ＜ 0.01).Conclusion Tacalcitol can promote melanocytes to proliferate,migrate,express c-kit mRNA,and adhere to fibronectin.

Expression and diagnostic significance of DOG1, CD117 and CD34 in gastrointestinal stromal tumors / 中国医师杂志

Objective To investigate the expression and diagnostic significance of DOG1,CD117and CD34 in gastrointestinal stromal tumors.Methods Expressions of DOG1,CD117 and CD34 were determined by immunohistochemical techniques (EnVision) in 60 cases of gastrointestinal stromal tumors (GIST) and 14 cases of other mesenchymal tumors.Results Expression of DOG1 in GIST was significantly higher than in other mesenchymal tumors (P =0.000).Expression of DOG1 in GIST from stomach was significantly higher than that from intestines.The expression rates of DOG1,CD117 and CD34 in GIST were 95％,95％,and 83.3％,respectively.Expression of DOG1 was significantly higher than CD34 (P =0.040),but no significant difference between DOG1 and CD117 (P =1.000).The expression rates of DOG1 in CD117-positive,CD34-positive tumors were 94.7％ and 94.1％,respectively.All the CD117-negative,CD34-negative tumors expressed DOG1,3 cases which were negative for CD117 and CD34 expressed DOG1.Conclusions DOG1 is a novel marker for GIST,It is necessary to the combined detection of the expression of DOG1,CD117 and CD34,which will further improve the diagnostic accuracy of GIST.

Diagnostic significance of c-kit and Ki-67 expression in the baseal cell adenoma and adenoid cystic carcinom of salivary gland / 肿瘤研究与临床

Objective To study the expression of c-kit and Ki-67 in the basal cell adenoma(BCA)and adenoid cystic carcinoma (ACC) of salivary gland. Methods The expression of c-kit and Ki-67 was determined by immunohistochemistry method in BCA and ACC of salivary gland. Results The positive immuostaining of c-kit in BCA and ACC were 72.2 ％(13/18) and 83.3 ％(35/42),respectively, There was no significant difference in the expression of c-kit between the two tissues (x2=0.11,P＞0.05).The expression of Ki-67 was significantly different between BCA[(3.72±1.41) ％]and ACC[(23.81±10.19)％](t=14.145,P＜0.01).Conclusion Detection of Ki-67 might be helpful to distinguish between BCA and ACC,but c-kit has no effect in differentiating BCA from ACC.

Tumores estromales gastrointestinales (GIST) en el Instituto Nacional de Cancerología, Bogota D.C., Colombia 2000-2008 / Gastrointestinal stromal tumors (GIST) at the National Cancer Institute, Bogota D.C., Colombia 2000-2008

Objetivo: Describir las características demográficas, clínicas y patológicas, así como el diagnóstico, el tratamiento y el seguimiento de los pacientes con tumores estromales gastrointestinales (GIST) del Instituto Nacional de Cancerología (INC) durante el periodo comprendido entre 2000 y 2008. Métodos: Estudio retrospectivo, de 39 pacientes con diagnóstico de GIST, donde se analizan las características clínicas los diagnósticos patológico y de inmunohistoquímica, al igual que los factores pronósticos, como tamaño, conteo mitótico y localización. Se revisa los manejos quirúrgico y médico, el seguimiento y la recurrencia, de acuerdo con la localización de las lesiones. Resultados: Se incluyó a 39 pacientes, con edad promedio de 53 años. La localización más habitual fue el estómago, con 16 casos, seguida del intestino delgado, con 9. De los pacientes, 24 presentaban lesiones mayores a 10 cm y, 19 con lesiones que microscópicamente mostraban menos de 5 mitosis x50 campos. Excepto una, todas las lesiones fueron positivas para CD117. El síntoma más habitual fue el dolor abdominal. De los 39 pacientes, 7 tenían metástasis al momento del diagnóstico. Al 43,7% de los pacientes se les tomó biopsia preoperatoria, y 38 pacientes fueron llevados a cirugía; 8 de ellos, por obstrucción intestinal con localización en el intestino delgado. El tiempo de seguimiento osciló entre 2 y 72 meses. Se presentaron 16 recaídas, con una tasa de 1,26 x 100 pacientes. La supervivencia media fue de 48,53 meses. Conclusiones: Los GIST son un grupo de tumores de mayor diagnóstico cada día, debido a la sospecha clínica y al diagnóstico por inmunohistoquímica. El manejo es, primordialmente, quirúrgico, pero en la actualidad la adyuvancia y la neoadyuvancia con ITK son parte del manejo de esta patología.

Objective: To describe the demographic, clinical and pathological characteristics, as well as diagnosis, treatment and follow up in patients with gastrointestinal stromal tumors (GIST) at the National Cancer Institute (NCI) between 2000 and 2008. Methods: A retrospective study was carried out on 39 patients diagnosed with GIST in which the diagnostic pathology and immunohistochemical clinical characteristics were analyzed, as were prognostic factors such as size, mitotic count and localization. Surgical and medical procedures along with follow up and recurrence were reviewed in relation to lesion localization. Results: The study included 39 patients with an average age of 53 years. Most common localization was the stomach (16 cases), followed by the small intestine (9 cases). Out of total number of patients, 24 had lesions greater than 10 cm. and 19 had lesions less than 5 mitosis x 50 fields. All but one lesion tested CD117 positive. Abdominal pain was the most common symptom. Of the 39 patients, 7 had metastasis at time of diagnosis. Preoperative biopsy was taken on 43.7% of patients, and 38 patients underwent surgery; 8 of whom for intestinal obstruction in the small intestine. Follow up ranged from 2 to 72 months. Relapse occurred in 16 cases, for a rate of 1.26 per 100 patients. Median survival rate was 48.53 months. Conclusions: GISTs make up a group of tumors with ever increasing diagnosis due to clinical suspicion and immunohistochemical diagnosis. Treatment is primarily surgical, but adjuvant and neo-adjuvant ITK treatment are currently used to treat this pathology.

Observation of the changes of protein gene product 9.5, mucosal C-kit, gastrin and somatostatin in rat with experimental induced gastritis / 中国医师杂志

Objective To find the possible pathogenesis of enteric nervous system, gut hormone and gastric Cajal interstitial cell ( ICC ) in gastritis related gastrointestinal ( GI ) motor disorders on the changes of protein gene product 9. 5 in neurons , mucosal expression of C-kit, gastrin and somatostatin from the gastric wall of gastritis rat. Methods 45 rats were divided into 3 groups which included gastritis group A, gastritis group B and control group. Rats in gastritis group A were fed with Hp Sydney Strain 1, the mixture of 2% aspirin and 0. 6N hydrochloric acid was fed in gastritis group B. The control group only received saline. All of the rats were killed and mucosal tissue was obtained from antrum and greater curvature of the gastric body. Pathological and Hp examination were performed in the tissue slides, and then it was stained to check PGP 9. 5, gastric body's mucosal expression of C-kit, antrium's mucosal expression of gastrin and somatostatin. The cell body, the maximum diameter (Dmax, μm), mean area( μm2) and optical density (nm), integral optical density of the gastrin and somatostatin in the C-kit expression positive neurons from the gastric wall were compared among the groups. Result The mean area and optical density of PGP 9. 5 expression in neurons from the gastric wall of rat in group A or B were obviously lower than that of the control group ( P ＜0. 01 ), while there was no difference between gastric group A and B ( P ＞0. 05). Gastric group A had higher GAS expression than control group, while SS expression was lower than control group( P＜0. 05). There was no difference between group B and the control group in the two variances( P ＞0. 05).By linear correlation analysis, it showed that SS was negatively correlated with GAS ( r = - 0. 333, P ＜0. 01 ). The distributive area and diameter of cells with C-kit expression in both group A and B were significantly smaller than that in the control group ( P ＜ 0. 05 ), while there was no obvious difference between group A and B ( P ＞ 0. 05 ). There was no difference of integral optical density of the C-kit expression positive neurons among the three groups. Conclusions Hp infection and NSAIDs might cause gastritis and had influence on the structural changes of neurons from gastric wall and ICC. Hp infection could obviously inhibit SS excretion from antrum mucosa while increase Gastrin excretion. NSAIDs induced gastritis had little influence on GAS and SS.

BRAF mutations in cutaneous melanoma: no correlation with histological prognostic factors or overall survival / Mutações BRAF em melanomas cutâneos: nenhuma correlação com fatores prognósticos e sobrevida global

INTRODUCTION: Molecular biology techniques allow identification of molecular markers such as BRAF and c-Kit gene mutations in melanomas. Studies on genetic alterations in melanomas of South-American patients are sparse. OBJECTIVES: To identify the incidence of BRAF and c-Kit gene mutations in primary cutaneous melanomas in Brazilian patients and to evaluate pathogenetic and prognostic implications of these mutations correlating them with clinical and histopathological data. MATERIAL AND METHODS: Ninety-six surgical specimens of primary cutaneous melanoma and 15 corresponding metastasis were analyzed using TaqMan Real-Time polymerase chain reaction (PCR) assays. RESULTS: In comparison with the medical literature, a relatively low frequency of BRAF mutation in primary (39 percent) and metastatic (40 percent) melanomas and complete absence of c-Kit gene mutations were demonstrated. BRAF mutations arose at an early stage during melanoma progression and were not involved in the transition of thin (< 1 mm) to thick (> 1 mm) melanomas. BRAF mutations are related to patients' younger age and to the pattern of sun exposure, although there was no correlation with any histological prognostic factor or overall survival. CONCLUSION: The identification of both BRAF and c-Kit mutation is not a suitable prognostic indicator in the Brazilian population. Moreover, the relatively low frequency of BRAF mutations brings into question if it actually plays a key role in melanoma pathogenesis.

INTRODUÇÃO: Técnicas de biologia molecular permitem a identificação de marcadores moleculares como mutações dos genes BRAF e c-Kit em melanomas. Estudos de alterações genéticas em pacientes sul-americanos são escassos. OBJETIVOS: Identificar a incidência de mutações dos genes BRAF e c-Kit em melanomas cutâneos primários em uma série de pacientes brasileiros e avaliar as implicações patogenéticas e prognósticas dessas mutações, correlacionando-as com dados clínicos e histopatológicos. MATERIAL E MÉTODOS: Noventa e seis espécimes cirúrgicos de melanomas cutâneos e 15 metástases correspondentes foram analisados por meio da técnica TaqMan Real-Time polymerase chain reaction (PCR). RESULTADOS: Uma frequência relativamente baixa de mutações BRAF em melanomas cutâneos primarios (39 por cento) e metastáticos (40 por cento) em comparação com os dados da literatura e ausência de mutações c-Kit foi demonstrado. Mutações BRAF surgiram em um estágio inicial da progressão do melanoma e não foram envolvidas na transição de melanomas finos (< 1 mm) para grossos (> 1 mm). Essas mutações estavam presentes em pacientes mais jovens e se correlacionaram com o padrão de exposição solar dos pacientes estudados, mas não houve correlação com nenhum fator prognóstico histológico ou sobrevida global dos mesmos. CONCLUSÃO: A identificação de ambas as mutações (BRAF e c-Kit) não servem como indicadores de prognóstico na população brasileira. Além disso, a baixa frequência de mutações BRAF encontrada neste estudo nos faz questionar se essa mutação realmente tem papel-chave na patogênese do melanoma.

Mastocitose sistêmica: relato de caso / Systemic mastocytosis: case report

A mastocitose sistêmica é um raro transtorno clonal dos mastócitos e de seus precursores. Embora de baixa incidência, a mastocitose sistêmica tem importância epidemiológica, pela morbimortalidade e pelo subdiagnóstico observados no nosso meio. Os sintomas da mastocitose sistêmica são advindos do acúmulo patogênico e da ativação dos mastócitos. Estudos recentes revelaram diferenças significativas entre a biologia celular e molecular dos mastócitos de indivíduos com mastocitose e de indivíduos normais. Esses achados podem ser usados tanto na formulação do critério diagnóstico quanto na elaboração de novas estratégias terapêuticas. É relatado caso de paciente do sexo masculino, 58 anos, com história de febre de origem indeterminada, astenia, adinamia, ascite e plaquetopenia internado no Hospital das Clínicas da UFMG com diagnóstico laboratorial de mastocitose sistêmica.

Systemic mastocytosis is a rare disturb of the mast cells and its progenitors. Even so the low incidence, the disease is epidemiologically important because of the high mortality and the misdiagnosed cases. The symptoms are due to systemic infiltration and activation of pathologic mast cells. Recent studies have documented the difference between the molecular and cellular biology of mast cells in patients with mastocytosis and those of healthy individuals. These findings are being used in formulating diagnostic criteria as well as dictating new treatment approaches to the disease. Is reported a clinic case of a male, 58 years old, with the history of fever of undetermined origin and malaise, ascitis and low platelets. The diagnosis criteria for systemic mastocytosis were established.

Mutation-Free Expression of c-Kit and PDGFRA in Phyllodes Tumors of the Breast / 한국유방암학회지

PURPOSE: Phyllodes tumors (PTs) of the breast have been classified as benign, borderline, or malignant based on their histopathologic features. However, predicting clinical behavior based on these features has proven to be difficult given that local recurrence occurs in both benign and malignant PTs. Recurrence has been shown to mirror the histologic pattern of the primary tumor or to show dedifferentiation. The aim of this study was to assess the value of the histopathologic parameters, expression or mutation of c-Kit and platelet derived growth factor receptor alpha (PDGFRA) in predicting tumor recurrence. METHODS: Representative areas from 39 benign, 16 borderline, and 12 malignant PTs were selected for construction of tissue microarrays. Immunohistochemical analyses for p53, Ki-67, c-Kit, and PDGFRA were performed and SSCP-PCR analysis was carried out to identify mutations in exons 9, 11, 13, and 17 of the c-Kit gene and exons 12 and 18 of the PDGFRA gene. Clinicopathologic features, including tumor recurrence and margin status, were also evaluated. RESULTS: Of the 67 PTs, 11 cases (16.4%) recurred from 3 to 92 months following initial diagnosis (4 benign, 2 borderline, and 5 malignant). One benign PT case recurred as a borderline tumor and two borderline PT cases recurred as malignancies. Three patients died of malignant PT. No mutations of the c-Kit or PDGFRA genes were found and there was no statistically significant association of either p53 or p16 immunostaining with recurrent disease (p>0.05). However, histologic grade (p=0.033), margin status (p<0.001), Ki-67 (p=0.012), c-Kit (p=0.002), and PDGFRA (p=0.007) stromal immunopositivity were significantly correlated with recurrence. CONCLUSION: Even though positive or close margins were significantly associated with tumor recurrence, stromal c-Kit, PDGFRA positivity, and the Ki-67 index were useful for predicting recurrent PTs. Despite this, no c-Kit or PDGFRA mutations were found.

Expression and significance of CD34, CD117 on bone marrow mononuclear cells of patients with myelodysplastic syndrome / 白血病·淋巴瘤

Objective To explore the expression and significance of CD34, CD117 on bone marrow mononuclear cells of myelodysplastic syndromes (MDS). Methods Direct immunofluorescence staining was used by means of flow cytometry. 37 patients with MDS were divided into RA/RARS/RCMD subgroup, RAEB Ⅰ/RAEB Ⅱ subgroup; favorable chromosomal subgroup, poor chromosomal subgroup; intermediate-risk Ⅰ subgroup, intermediate-risk Ⅱ subgroup, high-risk subgroup respectively according to WHO classification,cytogenetic abnormalities and international prognostic scoring system (IPSS). Results CD34 and CD117 were positive respectively in 11 of 19 patients with RMRARS/RCMD, all cases in RAEB Ⅰ/RAEB Ⅱ expressed CD34 and CD117; increased expression of CD34 and CD117 was MDS grade-related. Favorable chromosomal subgroup, 14 of 22 patients were positive for CD34, CD117, all cases in poor chromosomes expressed CD34 and CD117; there was a direct relationship between phenotytic density and poor cytogenetic risk factor. CD34 and CD117 expression was present respectively in intermediate-risk Ⅰ (9/17), intermediate-risk Ⅱ (11/11) and highrisk subgroup (9/9); the phenotypic intensity also was correlated with IPSS scores. Conclusion Detection of CD34, CD117 may be a useful tool for subtyping and predicting the prognosis of MDS.