RESUMO
BACKGROUND AND AIMS: Diffuse-type gastric cancer (GC) is currently subdivided into signet-ring cell carcinoma (SRCC) and non-SRCC, referred to as poorly cohesive carcinoma not otherwise specified (PCC-NOS). Although these subtypes are considered to be independent, they often coexist in the same tumors, raising a question of whether they clonally differ or not. To tackle this question, we established an experimental platform for human diffuse GC that enables accurate modeling of histologic subtypes. METHODS: Seven patient-derived diffuse GC organoid lines were established, characterized by histopathologic analysis, in situ hybridization, and gene expression analysis. For genetic modeling of diffuse GC, we knocked out CDH1 and/or TP53 in human normal gastric organoids. Green fluorescent protein-labeled GC organoids were xenotransplanted into immune-deficient mice for in vivo assessment. RESULTS: PCC-NOS organoids transformed into SRCC-like structures on removal of Wnt and R-spondin from the culture medium. This morphologic change paralleled downregulation of Wnt-target and gastric stem cell genes, including LGR5, and elevation of differentiation markers, such as KRT20 and MUCs. The association between Wnt target gene expression and histologic subtypes was confirmed in 3 patient-derived GC tissues. In vivo, single clone-derived organoids formed tumors that comprised 2 distinct histologic compartments, each corresponding to SRCC and PCC-NOS. The transition from PCC-NOS to SRCC histology reflected the abundance of surrounding R-spondin-expressing fibroblasts. CONCLUSIONS: SRCC and PCC-NOS were clonally identical, and their morphology was regulated by extracellular Wnt and R-spondin expression. Our results decoded how genetic mutations and the tumor environment shape pathohistologic and biologic phenotypes in human diffuse GCs.
Assuntos
Carcinoma de Células em Anel de Sinete/parasitologia , Mucosa Gástrica/patologia , Neoplasias Gástricas/patologia , Via de Sinalização Wnt , Idoso , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Caderinas/genética , Caderinas/metabolismo , Carcinoma de Células em Anel de Sinete/genética , Feminino , Mucosa Gástrica/citologia , Técnicas de Inativação de Genes , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Organoides/patologia , Cultura Primária de Células , RNA-Seq , Neoplasias Gástricas/genética , Trombospondinas , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Sequenciamento do Exoma , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Gastrointestinal anisakidosis is a nematode infection caused by the ingestion of larvae-infected raw or undercooked fish. The Japanese like to eat raw or undercooked fish, so gastric anisakiasis is a common disease in Japan. However, reports of anisakiasis with gastrointestinal cancer are rare. A 63-year-old Japanese male was diagnosed with a small early gastric cancerous lesion associated with gastric anisakiasis. From our experience and based on a review of the literature, the attachment of an anisakis larva to early gastric cancer is not considered accidental.
Assuntos
Anisaquíase/complicações , Anisakis/isolamento & purificação , Carcinoma de Células em Anel de Sinete/parasitologia , Carcinoma de Células em Anel de Sinete/cirurgia , Neoplasias Gástricas/parasitologia , Neoplasias Gástricas/cirurgia , Animais , Anisaquíase/parasitologia , Carcinoma de Células em Anel de Sinete/complicações , Carcinoma de Células em Anel de Sinete/patologia , Diagnóstico Precoce , Mucosa Gástrica/parasitologia , Humanos , Japão , Linfonodos/parasitologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologiaRESUMO
A definitive link between Schistosoma hematobium infection and squamous cell carcinoma of the bladder has been identified. A weaker association between S japonicum infection and colorectal neoplasia has been proposed, although reports are limited to case reports, a case series, and epidemiologic studies. Virtually all cases presented in the literature describe intestinal-type adenocarcinoma occurring in association with S japonicum. We here describe a 40-year-old male Filipino patient with signet ring cell carcinoma of the rectum and evidence of infection by S japonicum.
Assuntos
Carcinoma de Células em Anel de Sinete/parasitologia , Neoplasias Retais/parasitologia , Schistosoma japonicum/isolamento & purificação , Esquistossomose Japônica/parasitologia , Adulto , Animais , Anti-Helmínticos/uso terapêutico , Carcinoma de Células em Anel de Sinete/tratamento farmacológico , Carcinoma de Células em Anel de Sinete/patologia , Colostomia , Humanos , Masculino , Terapia Neoadjuvante , Praziquantel/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Esquistossomose Japônica/tratamento farmacológico , Esquistossomose Japônica/patologiaRESUMO
A 24-year-old male Egyptian complained of cramp-like upper abdominal discomfort and weight loss (3 kg) over 4 weeks. Physical examination merely gave evidence of the weight loss and of a slightly prominent gas-filled abdomen, mild diffuse abdominal tenderness and considerable borborygmus. Radiology of the intestines revealed chronic subileus of the small intestine caused by stenosis of the ileocaecal valve, which was impassable by coloscope. Biopsy suggested schistosomiasis of the ileocaecal valve. Examination of the resected ileocaecum showed a typical signet-ring carcinoma of the ileocaecal valve which had infiltrated all layers but had not metastasised to the regional lymph nodes (pT3, N0, M0). Typical eggs of Schistosoma haematobium were present in the mucosa of the tumour segment and of the neighbouring tissues. It is possible that chronic intestinal schistosomiasis is a potentially precancerous condition, similar to schistosomiasis of the urinary bladder.
