RESUMO
Small bowel adenocarcinoma (SBA) is a rare malignancy with a poor prognosis and limited treatment options. Despite prior studies, molecular characterization of this disease is not well defined, and little is known regarding Chinese SBA patients. In this study, we conducted multigene next-generation sequencing and 16S ribosomal RNA gene sequencing on samples from 76 Chinese patients with surgically resected primary SBA. Compared with colorectal cancer and Western SBA cohorts, a distinctive genomic profile was revealed in Chinese SBA cohorts. According to the levels of clinical actionability to targetable alterations stratified by OncoKB system, 75% of patients harbored targetable alterations, of which ERBB2, BRCA1/2, and C-KIT mutations were the most common targets of highest-level actionable alterations. In DNA mismatch repair-proficient (pMMR) patients, significant associations between high tumor mutational burden and specific genetic alterations were identified. Moreover, KRAS mutations/TP53 wild-type/nondisruptive mutations (KRASmut /TP53wt/non-dis ) were independently associated with an inferior recurrence-free survival (hazard ratio [HR] = 4.21, 95% confidence interval [CI] = 1.94-9.14, P < .001). The bacterial profile revealed Proteobacteia, Actinobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Cyanobacteria were the most common phyla in SBA. Furthermore, patients were clustered into three subgroups based on the relative abundance of bacterial phyla, and the distributions of the subgroups were significantly associated with the risk of recurrence stratified by TP53 and KRAS mutations. In conclusion, these findings provided a comprehensive molecular basis for understanding SBA, which will be of great significance in improving the treatment strategies and clinical management of this population.
Assuntos
Adenocarcinoma/genética , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Intestinais/genética , Intestino Delgado , RNA Ribossômico 16S/genética , Adenocarcinoma/microbiologia , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Reparo de Erro de Pareamento de DNA , Intervalo Livre de Doença , Neoplasias Duodenais/genética , Neoplasias Duodenais/microbiologia , Neoplasias Duodenais/mortalidade , Feminino , Microbioma Gastrointestinal , Genes BRCA1 , Genes BRCA2 , Genes p53 , Genes ras , Humanos , Neoplasias do Íleo/genética , Neoplasias do Íleo/microbiologia , Neoplasias do Íleo/mortalidade , Neoplasias Intestinais/microbiologia , Neoplasias Intestinais/mortalidade , Intestino Delgado/microbiologia , Neoplasias do Jejuno/genética , Neoplasias do Jejuno/microbiologia , Neoplasias do Jejuno/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-kit/genética , Receptor ErbB-2/genéticaRESUMO
The current understanding of clinicopathological features and genomic variants of small-bowel cancer is limited, in part due to the rarity of the disease. However, understanding of these factors is necessary for the development of novel therapeutic agents for small-bowel cancer. Thus, we aimed to identify the clinicopathological features and genomic variants associated with its prognosis and recurrence. We retrospectively examined 24 consecutive patients with primary small-bowel cancer surgically treated between May 2005 and August 2018 and collected 29 tumor specimens. The 29 lesions were subjected to mismatch repair status evaluation, using immunohistochemistry (IHC), and targeted genomic sequencing, after which they were analyzed using a panel of 90 cancer-related genes. IHC revealed that 45% (13/29) of the lesions exhibited deficient mismatch repair. The most common genomic variants in small-bowel cancers were in TP53 (48%, 13/27), followed by KRAS (44%, 12/27), ARID1A (33%, 9/27), PIK3CA (26%, 7/27), APC (26%, 7/27), and SMAD4, NOTCH3, CREBBP, PTCH1, and EP300 (22%, 6/27 each). Overall survival and disease-specific survival of patients with tumor mutational burden (TMB) ≥10 mutations/Mb (n = 17) were significantly better than those of patients with TMB <10 mutations/Mb (n = 6). Additionally, patients with a mutant SMAD4 had poorer recurrence-free survival than those with wild-type SMAD4. Our results suggested that TMB and SMAD4 mutations were associated with the prognosis of small-bowel cancer patients. Thus, cancer genomic analysis could be useful in the search for biomarkers of prognosis prediction in small-bowel cancers.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Íleo/genética , Neoplasias do Jejuno/genética , Mutação , Adulto , Idoso , Proteína de Ligação a CREB/genética , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Neoplasias do Íleo/patologia , Neoplasias do Jejuno/patologia , Masculino , Pessoa de Meia-Idade , Receptores Notch/genética , Proteínas Smad/genética , Análise de Sobrevida , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/genética , Proteínas ras/genéticaRESUMO
PURPOSE: Small-bowel adenocarcinoma (SBA) is rare, and no standard of care exists for metastatic disease beyond first-line FOLFOX/CAPOX. SBA has higher rates of microsatellite instability (MSI-H) and T-lymphocyte infiltration than other gastrointestinal cancers. We hypothesize that pembrolizumab, a PD-1 inhibitor, will induce antitumor response. PATIENTS AND METHODS: Patients with previously treated advanced SBA received pembrolizumab 200 mg i.v. every 3 weeks until disease progression (PD), toxicity, or 35 doses maximum. Primary endpoint was confirmed overall response rate (ORR) with secondary progression-free survival (PFS), overall survival (OS), and toxicity assessment endpoints. Outcomes were stratified by tumor location, microsatellite stability (MSS) or instability (MSI-H), and PD-L1 level. RESULTS: Forty patients were treated for a median duration of four cycles (range, 1-35). All patients are off study treatment due to PD (75%), death (10%), 35 cycles completed (8%), refusal (3%), and adverse effects (AEs, 5%). Three confirmed partial responses [PRs; 8%; 95% confidence interval (CI), 2-20] did not meet predefined success criteria of ORR 30%. Median OS (7.1 months; 95% CI, 5.1-17.1) and median PFS (2.8 months; 95% CI, 2.7-4.2) were similar across primary tumor sites. One confirmed PR (3%) was seen in patients with low MSS/MSI tumors and correlated with high tumor mutation burden (TMB). Fifty percent of patients with MSI-H tumors achieved PR and remain alive without progression. Twenty-five patients (63%) had grade ≥3 AEs and 11 patients (28%) had grade 4/5 AEs. CONCLUSIONS: In the largest study of SBA to date, pembrolizumab did not induce the hypothesized response rate; however, we did identify responses in key biomarker-selected cohorts.
Assuntos
Adenocarcinoma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Duodenais/tratamento farmacológico , Neoplasias do Íleo/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias do Jejuno/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Duodenais/genética , Neoplasias Duodenais/patologia , Feminino , Humanos , Neoplasias do Íleo/genética , Neoplasias do Íleo/patologia , Neoplasias do Jejuno/genética , Neoplasias do Jejuno/patologia , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Resultado do TratamentoRESUMO
Background: Small bowel adenocarcinoma (SBA) is a dreadful disease. Patient prognosis is limited due to late presentation and ineffective chemotherapy. PD-1/PD-L1 checkpoint immunotherapy is regarded as a promising approach in several cancer entities. The association of PD-1/PD-L1 expression and its impact on patient prognosis with SBA is unclear. Material and methods: Seventy-five consecutive patients who underwent surgery for SBA were retrospectively analyzed and stained for PD-L1 expression in the tumour or the stroma. Analysis of mismatch repair genes was performed to determine microsatellite status. Kaplan-Meier estimate was used to analyze patient survival. Univariate and multivariable Cox regression-analyses were used to assess the impact of PD-L1 expression and microsatellite status on patient survival.Results: PD-L1 was weakly upregulated within the tumour or the stroma and associated with prolonged survival (p = .0071 and p = .0472, respectively). Fifty-one tumours (68%) revealed microsatellite stability (MSS) and 24 tumours (32%) were microsatellite instable (MSI) without correlating with patient survival (p = .611). Neither PD-L1 expression in the tumour nor in the stroma was identified as an independent risk factor influencing survival (p = .572 and p = .3055).Conclusion: Although PD-L1 expression is associated with prolonged survival, it was not identified as an independent prognostic marker. Microsatellite status did not influence long-term survival.
Assuntos
Adenocarcinoma/patologia , Antígeno B7-H1/genética , Neoplasias Duodenais/patologia , Neoplasias do Íleo/patologia , Neoplasias do Jejuno/patologia , Instabilidade de Microssatélites , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias Duodenais/genética , Neoplasias Duodenais/mortalidade , Feminino , Humanos , Neoplasias do Íleo/genética , Neoplasias do Íleo/mortalidade , Imuno-Histoquímica , Neoplasias do Jejuno/genética , Neoplasias do Jejuno/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
RATIONALE: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract and is characterized by KIT mutations. Patientsresistant to 1st-line imatinib therapy are usually given sunitinib assecond-line treatment, which provides a median progression-free survival of 8 to 12 months. We report the 1st case of metastatic jejunum GIST with a KIT exon 11 deletion that showed complete response (CR) to sunitinib for more than 3 years. PATIENT CONCERNS: A 34-year-old man with advanced jejunum GIST was surgically treated upon initial diagnosis, and was histologically found to carry a high recurrence risk. Genetic testing revealed a KIT exon 11 deletion, and adjuvant therapy with imatinib was administered. The imatinib dose was escalated following recurrence in the abdomen, but the mass continued to grow. DIAGNOSIS: He was diagnosed with abdominal recurrence of GIST based on his medical history and histopathological results. INTERVENTION: Second-line sunitinib therapy was given. OUTCOMES: The mass disappeared, and CR was seen following 7 months of sunitinib therapy; this CR was sustained for more than 45 months. LESSONS: In cases of metastatic jejunum GIST with a KIT exon 11 deletion, sunitinib as second-line therapy can be used to achieve CR for more than 3 years.
Assuntos
Antineoplásicos/administração & dosagem , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Neoplasias do Jejuno/tratamento farmacológico , Sunitinibe/administração & dosagem , Adulto , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Éxons , Tumores do Estroma Gastrointestinal/genética , Humanos , Quimioterapia de Indução , Neoplasias do Jejuno/genética , Masculino , Mutação , Proteínas Proto-Oncogênicas c-kit/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-kit/genética , Fatores de Tempo , Resultado do TratamentoAssuntos
Linfoma Folicular/genética , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Idoso de 80 Anos ou mais , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Evolução Fatal , Humanos , Neoplasias do Jejuno/genética , Neoplasias do Jejuno/patologia , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologiaRESUMO
Gastric polyposis is a rare disease. Not all polyps progress to cancer. Monoallelic mutation in Fanconi anemia (FA) genes, unlike biallelic gene mutations that causes typical FA phenotype, can increase risks of cancers in a sporadic manner. Aberrations in the FA pathway were reported in all molecular subtypes of gastric cancer. We studied a patient with synchronous gastric cancer from gastric polyposis by conducting a 13-year long-term follow up. Via pathway-driven massive parallel genomic sequencing, a germline mutation at FANCA D1359Y was identified. We identified several recurrent mutations in DNA methylation (TET1, V873I), the ß-catenin pathway (CTNNB1, S45F) and RHO signaling pathway (PLEKHG5, R203C) by comparing the genetic events between benign and malignant gastric polyps. Furthermore, we revealed gastric polyposis susceptible genes and genetic events promoting malignant transformation using pathway-driven targeted gene sequencing.
Assuntos
Pólipos Adenomatosos/genética , Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Predisposição Genética para Doença , Neoplasias do Jejuno/genética , Neoplasias Gástricas/genética , Pólipos Adenomatosos/complicações , Pólipos Adenomatosos/diagnóstico por imagem , Pólipos Adenomatosos/patologia , Idoso , Anemia Ferropriva/etiologia , Biópsia , Análise Mutacional de DNA , Gastrectomia , Hemorragia Gastrointestinal/etiologia , Gastroscopia , Humanos , Neoplasias do Jejuno/diagnóstico por imagem , Neoplasias do Jejuno/patologia , Neoplasias do Jejuno/cirurgia , Jejuno/diagnóstico por imagem , Jejuno/patologia , Jejuno/cirurgia , Masculino , Mutação , Estômago/diagnóstico por imagem , Estômago/patologia , Estômago/cirurgia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios XRESUMO
A 77-year-old patient was admitted to our hospital for the further examination of melena. A computed tomography scan detected two submucosal tumors (SMTs) in the stomach and jejunum. Double-balloon endoscopy revealed the presence of a delle on the jejunal SMT, suggesting that the SMT was the origin of the gastrointestinal bleeding. Both tumors were surgically resected and subsequently diagnosed via histology as gastrointestinal stromal tumors (GISTs). Furthermore, the two GISTs had different mutations in the c-kit gene, suggesting that they were derived from different clonal origins. This report depicts an extremely rare case of multiple synchronous sporadic GISTs in the stomach and jejunum.
Assuntos
Tumores do Estroma Gastrointestinal/patologia , Neoplasias do Jejuno/patologia , Neoplasias Gástricas/patologia , Idoso , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/genética , Humanos , Neoplasias do Jejuno/genética , Jejuno , Masculino , Proteínas Proto-Oncogênicas c-kit/genética , Neoplasias Gástricas/genética , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Malignant gastrointestinal neuroectodermal tumor (GNET) is an extremely rare entity that was first described by Zambrano et al. in 2003 as "Clear cell sarcoma-like tumor of the gastrointestinal tract". It shares some of the histological features of clear cell sarcoma (CCS) but lacks the immunohistochemical reactivity for melanocytic markers. We report a case of GNET that was initially misdiagnosed as gastrointestinal stromal tumor (GIST). Recognizing this entity is important to avoid misdiagnosis. CASE PRESENTATION: A case of an 18-year-old male presented with a small intestinal tumor. Histologically it was characterized by polygonal cells arranged in pseudoalveolar pattern and situated in the muscularis propria. Scattered osteoclast-like multinucleated giant cells were also noted. The neoplastic cells were positive for S-100 protein and negative for HMB-45, Melan A, smooth muscle actin, desmin and CD117. EWSR1 gene rearrangement was detected by fluorescence in situ hybridization (FISH) analysis. The patient returned with recurrence after 36 months' management by surgical resection and died one year later. CONCLUSIONS: GNET can be mistaken histologically for other non-epithelial gastrointestinal tumors. Awareness of its existence and diagnostic criteria by the pathologist is necessary to avoid misdiagnosis, particularly as GIST, CCS or malignant peripheral nerve sheath tumor (MPNST).
Assuntos
Tumores do Estroma Gastrointestinal/patologia , Neoplasias do Jejuno/patologia , Tumores Neuroectodérmicos/patologia , Adolescente , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Proteínas de Ligação a Calmodulina/genética , Erros de Diagnóstico , Evolução Fatal , Tumores do Estroma Gastrointestinal/química , Tumores do Estroma Gastrointestinal/genética , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias do Jejuno/química , Neoplasias do Jejuno/genética , Neoplasias do Jejuno/cirurgia , Masculino , Recidiva Local de Neoplasia , Tumores Neuroectodérmicos/química , Tumores Neuroectodérmicos/genética , Tumores Neuroectodérmicos/cirurgia , Valor Preditivo dos Testes , Proteína EWS de Ligação a RNA , Proteínas de Ligação a RNA/genética , Fatores de Tempo , Resultado do TratamentoAssuntos
Síndrome do Hamartoma Múltiplo/diagnóstico , Neoplasias do Jejuno/diagnóstico , Biomarcadores Tumorais/genética , Biópsia , Análise Mutacional de DNA , Predisposição Genética para Doença , Síndrome do Hamartoma Múltiplo/genética , Síndrome do Hamartoma Múltiplo/patologia , Síndrome do Hamartoma Múltiplo/cirurgia , Humanos , Neoplasias do Jejuno/genética , Neoplasias do Jejuno/patologia , Neoplasias do Jejuno/cirurgia , Masculino , Mutação , PTEN Fosfo-Hidrolase/genética , Fenótipo , Resultado do Tratamento , Adulto JovemRESUMO
Multiple primary malignancy is defined as two or more malignancies detected in an individual person. In particular, synchronous quintuple primary malignancy is extremely rare. A 52-year-old male with anal pain and intermittent blood-tinged stool was diagnosed with malignancies in the stomach, jejunum, ascending colon, transverse colon and rectum. He underwent a subtotal gastrectomy, segmental resection of the jejunum and total protocolectomy with end ileostomy. The postoperative pathologic findings were moderate differentiated gastric adenocarcinoma (pT1bN0M0, pStageIA), combined adenocarcinoma and neuroendocrine carcinoma of the jejunum (pT3N0M0, pStageIIA), three mucinous adenocarcinoma of the ascending colon (pT3N0M0, pStageIIA), transverse colon (pT1N0M0, pStageI) and rectum (pT3N1aM0, pStageIIIB). The tumors did not lack MLH-1 and MSH-2 expression, as the markers (bat26, D5S346, bat25, D2S123) suggest MSI-H presence. Adjuvant chemoradiotherapy was started according to regimen, FOLFOX 4 for advanced rectal cancer. Six years post-operation, the patient is currently attending regular follow-ups without recurrence or metastasis.
Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Neoplasias do Colo/diagnóstico , Neoplasias do Jejuno/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Retais/diagnóstico , Neoplasias Gástricas/diagnóstico , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Dor do Câncer/etiologia , Quimiorradioterapia Adjuvante , Colectomia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Endoscopia Gastrointestinal , Fluoruracila/uso terapêutico , Gastrectomia/métodos , Hemorragia Gastrointestinal/etiologia , Humanos , Ileostomia , Neoplasias do Jejuno/genética , Neoplasias do Jejuno/patologia , Neoplasias do Jejuno/terapia , Leucovorina/uso terapêutico , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/terapia , Compostos Organoplatínicos/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Retais/genética , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND & AIMS: Small intestinal neuroendocrine tumors (SI-NETs) are serotonin-secreting well-differentiated neuroendocrine tumors believed to originate from enterochromaffin (EC) cells. Intestinal stem cell (ISC) are believed to contribute to the formation of SI-NETs, although little is known about tumor formation or development. We investigated the relationship between EC cells, ISCs, and SI-NETs. METHODS: We analyzed jejuno-ileal tissue specimens from 14 patients with familial SI-NETs enrolled in the Natural History of Familial Carcinoid Tumor study at the National Institutes of Health from January 2009 to December 2014. Frozen and paraffin-embedded tumor tissues of different stages and isolated crypts were analyzed by in situ hybridization and immunohistochemistry. Tumor clonality was assessed by analyses of mitochondrial DNA. RESULTS: We identified multifocal aberrant crypt-containing endocrine cell clusters (ACECs) that contain crypt EC cell microtumors in patients with familial SI-NETs. RNA in situ hybridization revealed expression of the EC cell and reserve stem cell genes TPH1, BMI1, HOPX, and LGR5(low), in the ACECs and more advanced extraepithelial tumor nests. This expression pattern resembled that of reserve EC cells that express reserve ISC genes; most reside at the +4 position in normal crypts. The presence of multifocal ACECs from separate tumors and in the macroscopic tumor-free mucosa indicated widespread, independent, multifocal tumorigenesis. Analyses of mitochondrial DNA confirmed the independent origin of the ACECs. CONCLUSIONS: Familial SI-NETs originate from a subset of EC cells (reserve EC cells that express reserve ISC genes) via multifocal and polyclonal processes. Increasing our understanding of the role of these reserve EC cells in the genesis of multifocal SI-NETs could improve diagnostic and therapeutic strategies for this otherwise intractable disease.
Assuntos
Carcinogênese/genética , Neoplasias do Íleo/genética , Neoplasias do Jejuno/genética , Família Multigênica/genética , Tumores Neuroendócrinos/genética , Células Enterocromafins/metabolismo , Proteínas de Homeodomínio/genética , Humanos , Hibridização In Situ , Intestino Delgado/citologia , Complexo Repressor Polycomb 1/genética , Receptores Acoplados a Proteínas G/genética , Células-Tronco/metabolismo , Triptofano Hidroxilase/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
AIMS AND BACKGROUND: PIK3CA mutations involving exons 9 and 20 are among the most common aberrations seen in human malignancies. The identification of PIK3CA mutations in small bowel adenocarcinoma (SBA) is sparse. There is some evidence that tumors with this mutation may be a good target for inhibitors of the PI3K pathway. CASE REPORT: We report an exon 9 (G1624A: E542K) hot spot mutation in a 69-year-old man with sporadic jejunal cancer (T3, N1). A systemic search was made for other reports using Medline/Embase along with Sangers Institute Cancer Genome Project database. We analyzed and describe this mutation in these patients, including one of ours. RESULTS AND CONCLUSION: A total of 8 tumor samples with confirmed somatic mutations out of a total of 86 samples were noted: rate 9.3% (95% confidence interval 4.5% to 17.5%). Overall, PIK3CA mutations were more common in duodenum (62.5%) and located most commonly on exon 9. The significance of PIK3CA mutation in SBA is unclear. Further studies on mutation analysis in larger cohorts with SBA are in order to identify and confirm relationships between these mutations and various clinical and pathologic variables such as age, lymph node status, distant metastasis, stage, and progression-free survival and association with other gene mutations.
Assuntos
Adenocarcinoma/genética , Neoplasias do Jejuno/genética , Mutação , Fosfatidilinositol 3-Quinases/genética , Idoso , Classe I de Fosfatidilinositol 3-Quinases , Intervalo Livre de Doença , Éxons , Humanos , MasculinoRESUMO
Clear cell sarcoma (CCS) of the tendons and aponeuroses is a rare soft tissue sarcoma that morphologically resembles cutaneous malignant melanoma but exhibits a distinct molecular profile. Gastrointestinal (GI) CCS is extremely rare. In this study, two cases of CCS were presented: (1) left thumb and (2) jejunum. Case 1 manifested the characteristic CCS morphology. Case 2 was morphologically unusual and difficult to diagnose. Immunohistochemically, the two cases of tumor cells were diffusely positive for S100, vimentin, NSE protein, focal expression of CgA, and CAM2.5 protein. In case 1, the tumor cells were diffusely positive for HMB45, focal expression of CD56, and melan A antigen. Reverse transcriptase-polymerase chain reaction (RT-PCR) results confirmed the presence of the EWS/ATF1 translocation (type 1) in the two cases. Then, we detected 19 hotspot oncogenes in the two cases. To the best of our knowledge, this study is the first to apply a high-throughput OncoCarta panel 1.0 and MassARRAY system to detect 238 known mutations in 19 hotspot oncogenes in soft tissue clear cell sarcoma. In this study, no mutations were observed in these hotspot oncogenes in the two cases.
Assuntos
Neoplasias do Jejuno/genética , Sarcoma de Células Claras/genética , Adulto , Idoso , Biomarcadores Tumorais/análise , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Neoplasias do Jejuno/patologia , Masculino , Proteínas de Fusão Oncogênica/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sarcoma de Células Claras/patologia , Análise de Sequência de DNA , Polegar/patologia , Fatores de Transcrição/genéticaRESUMO
PURPOSE: To investigate whether celiac disease risk haplotypes HLA-DQ2 and DQ8 also increase the risk for developing small intestinal neuroendocrine tumor (SI-NET). METHODS: Thirty-five patients with serotonin-producing jejunal and ileal SI-NET were examined with HLA-DQ genotyping and serology for IgA anti-tissue transglutaminase (tTG) antibodies. RESULTS: Twenty-one patients (60 %) carried HLA-DQ2 or DQ8, twice the frequency of the general population (P < 0.001). In particular DQ2 was overrepresented (P = 0.013). Gender, age, disease stage, histopathological grade, or multifocality of primary tumor did not differ between patients with DQ2 or DQ8 and patients with other HLA-DQ haplotypes. No patient in the study was diagnosed with celiac disease (latent or symptomatic) as anti-tTG antibodies were negative in all 35. CONCLUSION: HLA-DQ haplotypes associated with celiac disease are overrepresented also in patients with SI-NET, in particular HLA-DQ2.
Assuntos
Antígenos HLA-DQ/biossíntese , Neoplasias do Íleo/imunologia , Neoplasias do Jejuno/imunologia , Tumores Neuroendócrinos/imunologia , Feminino , Predisposição Genética para Doença , Antígenos HLA-DQ/genética , Antígenos HLA-DQ/imunologia , Haplótipos , Humanos , Neoplasias do Íleo/genética , Neoplasias do Jejuno/genética , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/genéticaRESUMO
Jejunal carcinoma in patients with familial adenomatous polyposis has been rarely reported, and little is known about its association with genetic alterations of the APC gene. A 52-year-old woman with familial adenomatous polyposis underwent palliative resection of the proximal jejunum because of two circumferential tumors associated with peritoneal carcinomatosis. A histological examination revealed that one tumor was a poorly differentiated adenocarcinoma, and that the other was a moderately differentiated adenocarcinoma with adenomatous components. The patient did not respond to standard chemotherapy and died of disseminated disease 8 months after surgery. A genetic analysis of the APC gene identified somatic mutations in each tumor (c.4450delAG and p.R1450X) in addition to the germline mutation (c.3984del5), all of which form stop codons, resulting in truncated APC products. This report is the first description of how a second hit to the APC gene can be involved in carcinogenesis of the jejunum in familial adenomatous polyposis.
Assuntos
Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/cirurgia , Carcinoma/genética , Genes APC , Mutação em Linhagem Germinativa , Neoplasias do Jejuno/genética , Adenocarcinoma/genética , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/patologia , Resistencia a Medicamentos Antineoplásicos , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade , Cuidados Paliativos/métodosRESUMO
Large single-institution series of patients undergoing resection for gastrointestinal stromal tumors (GIST) are lacking. Clinicopathologic characteristics and postoperative outcomes were retrospectively collected and analyzed from patients undergoing resection for GIST from 2002 to 2011. One hundred seventy-six patients were identified; 156 underwent resection of primary nonmetastatic disease. KIT mutations were identified in 131 patients (84.0%). Of the 156 patients with primary disease, the most common site was the stomach (75.6%). Tumors were categorized as very low (24.4%), low (35.9%), intermediate (12.2%), high (24.4%), or unknown (3.2%) risk. Symptomatic patients more often had high risk (35.6 vs 9.8%; P < 0.0001) and larger tumors (7.3 vs 3.0 cm; P < 0.0001). Forty-seven patients (30.1%) underwent laparoscopic resection (LR). Compared with open surgery, LR was performed for smaller tumors (3.8 vs 6.2 cm; P = 0.002). Positive margin rates were similar (4.3% LR vs 10.2% open; P = 0.346). Median follow-up for the 156 patients with primary tumors was 32.9 months; mean overall survival was 120.9 months (median not reached). Of the 20 patients with metastatic GIST (excluded from above analysis), five patients (25.0%) died of disease with a median follow-up of 15.9 months. Most patients with resectable primary GIST have a favorable prognosis. The presence of symptoms directly related to GIST may be associated with a poor prognosis and is likely related to increased tumor size. Laparoscopic resection is well tolerated and does not appear to compromise outcomes in well-selected patients. Highly selected patients with metastatic disease may benefit from resection.
Assuntos
Tumores do Estroma Gastrointestinal/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Duodenais/genética , Neoplasias Duodenais/patologia , Neoplasias Duodenais/cirurgia , Feminino , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Humanos , Neoplasias do Jejuno/genética , Neoplasias do Jejuno/patologia , Neoplasias do Jejuno/cirurgia , Laparoscopia , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Prognóstico , Proteínas Proto-Oncogênicas c-kit/genética , Estudos Retrospectivos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: To study the clinicopathologic features, immunohistochemical findings, differential diagnosis and prognosis of type II enteropathy-associated T-cell lymphoma (EATL). METHODS: Fourteen cases of type II EATL encountered in Department of Pathology, Nanjing General Hospital were retrospectively reviewed. The clinical data, histologic features, immunohistochemical findings and follow-up information were analyzed, with literature review. RESULTS: There were altogether 12 males and 2 females. The median age of patient was 49 years. The sites of involvement included jejunum (10 cases) and ileum/colon (4 cases). The patients often presented with an abdominal mass, abdominal pain, diarrhea and constitutional symptoms such as fever, night sweating and cachexia. There was no clinical evidence of gluten-sensitive enteropathy. Histologically, the lymphoma cells showed full-thickness infiltration of the intestinal wall. They contained round hyperchromatic nuclei and pale cytoplasm. The stroma was minimally inflamed, with or without associated coagulative necrosis. A remarkable finding was the presence of villous atrophy, cryptal hyperplasia and intraepithelial lymphocytosis. Immunohistochemical study showed that the tumor cells expressed CD3, CD43 and CD8 (14/14). Some of them were also positive for CD56 (11/14) and CD30 (2/14). The staining for CD4, CD20, CD79a and myeloperoxidase was negative. A high proliferation index was demonstrated by Ki-67 immunostain. In-situ hybridization for EBER was negative. Follow-up data were available in 9 cases. The duration of follow-up ranged from 6 months to 36 months. Seven patients died within 14 months. CONCLUSIONS: EATL is a rare type of lymphoma with intestinal involvement. Associated enteropathy is not demonstrated, in contrast to cases encountered in Nordic countries. A correct diagnosis requires evaluation of clinical manifestations, pathologic features and ancillary study results.