Subject(s)
Esophageal Stenosis/diagnosis , Intestinal Diseases/epidemiology , Stevens-Johnson Syndrome/complications , Adult , Endoscopy, Gastrointestinal , Esophageal Mucosa/diagnostic imaging , Esophageal Mucosa/immunology , Esophageal Stenosis/epidemiology , Esophageal Stenosis/immunology , Female , Hospital Mortality , Hospitalization , Humans , Intestinal Diseases/diagnosis , Intestinal Diseases/immunology , Intestinal Mucosa/diagnostic imaging , Intestinal Mucosa/immunology , Male , Middle Aged , Retrospective Studies , Stevens-Johnson Syndrome/immunologyABSTRACT
BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) syndrome is a childhood cancer predisposition syndrome involving biallelic germline mutations of MMR genes, poorly recognised by clinicians so far. METHODS: Retrospective review of all 31 patients with CMMRD diagnosed in French genetics laboratories in order to describe the characteristics, treatment and outcome of the malignancies and biological diagnostic data. RESULTS: 67 tumours were diagnosed in 31 patients, 25 (37%) Lynch syndrome-associated malignancies, 22 (33%) brain tumours, 17 (25%) haematological malignancies and 3 (5%) sarcomas. The median age of onset of the first tumour was 6.9â years (1.2-33.5). Overall, 22 patients died, 9 (41%) due to the primary tumour. Median survival after the diagnosis of the primary tumour was 27â months (0.26-213.2). Failure rate seemed to be higher than expected especially for T-cell non-Hodgkin's lymphoma (progression/relapse in 6/12 patients). A familial history of Lynch syndrome was identified in 6/23 families, and consanguinity in 9/23 families. PMS2 mutations (n=18) were more frequent than other mutations (MSH6 (n=6), MLH1 (n=4) and MSH2 (n=3)). CONCLUSIONS: In conclusion, this unselected series of patients confirms the extreme severity of this syndrome with a high mortality rate mostly related to multiple childhood cancers, and highlights the need for its early detection in order to adapt treatment and surveillance.
Subject(s)
Brain Neoplasms/diagnosis , Colorectal Neoplasms/diagnosis , Neoplastic Syndromes, Hereditary/diagnosis , Adaptor Proteins, Signal Transducing/genetics , Adenosine Triphosphatases/genetics , Adolescent , Adult , Brain Neoplasms/genetics , Brain Neoplasms/therapy , Child , Child, Preschool , Colorectal Neoplasms/genetics , Colorectal Neoplasms/therapy , DNA Repair Enzymes/genetics , DNA-Binding Proteins/genetics , Female , Humans , Infant , Male , Mismatch Repair Endonuclease PMS2 , MutL Protein Homolog 1 , MutS Homolog 2 Protein/genetics , Mutation , Neoplastic Syndromes, Hereditary/genetics , Neoplastic Syndromes, Hereditary/therapy , Nuclear Proteins/genetics , Treatment Outcome , Young AdultABSTRACT
The molecular basis for the resistance of tumor cells to cell-mediated cytotoxicity remains poorly understood and thus poses a major challenge for cancer immunotherapy. The present study was designed to determine whether the WNT1-inducible signaling pathway protein 2 (WISP2, also referred to as CCN5), a key regulator of tumor cell plasticity, interferes with tumor susceptibility to cytotoxic T-lymphocyte (CTL)-mediated lysis. We found that silencing WISP2 signaling in human breast adenocarcinoma MCF7 cells impairs CTL-mediated cell killing by a mechanism involving stem cell marker Kruppel-like factor-4 (KLF-4) induction and microRNA-7 (miR-7) downregulation. Inhibition of transforming growth factor beta (TGF-ß) signaling using the A83-01 inhibitor in MCF7-shWISP2 cells resulted in a significant reversal of the epithelial-to-mesenchymal-transitioned (EMT) phenotype, the expression of KLF-4 and a partial recovery of target susceptibility to CTLs. More importantly, we showed that silencing KLF-4 was accompanied by a reduction in MCF7-shWISP2 resistance to CTLs. Using human breast cancer tissues, we demonstrated the coexpression of KLF-4 with EMT markers and TGF-ß pathway signaling components. More importantly, we found that KLF-4 expression was accompanied by miR-7 inhibition, which is partly responsible for impairing CTL-mediated lysis. Thus, our data indicate that WISP2 has a role in regulating tumor cell susceptibility through EMT by inducing the TGF-ß signaling pathway, KLF-4 expression and miR-7 inhibition. These studies indicate for the first time that WISP2 acts as an activator of CTL-induced killing and suggests that the loss of its function promotes evasion of immunosurveillance and the ensuing progression of the tumor.
Subject(s)
Breast Neoplasms/immunology , CCN Intercellular Signaling Proteins/immunology , Gene Expression Regulation, Neoplastic/immunology , Immunity, Cellular , Kruppel-Like Transcription Factors/immunology , MicroRNAs/immunology , RNA, Neoplasm/immunology , Repressor Proteins/immunology , T-Lymphocytes/immunology , Breast Neoplasms/pathology , CCN Intercellular Signaling Proteins/genetics , Cell Line, Tumor , Female , Humans , Kruppel-Like Factor 4 , Kruppel-Like Transcription Factors/genetics , MicroRNAs/genetics , Neoplasm Proteins/genetics , Neoplasm Proteins/immunology , RNA, Neoplasm/genetics , Repressor Proteins/genetics , T-Lymphocytes/pathology , Wnt Signaling PathwaySubject(s)
Neurilemmoma/diagnostic imaging , Retroperitoneal Neoplasms/diagnostic imaging , Adult , Female , Humans , RadiographyABSTRACT
Uterine lipomas are uncommon. Several histology hypotheses are described. Ultrasound is firstly performed but diagnosis is sometimes difficult. Magnetic resonance imaging is more specific and helpful to make a differential diagnosis with a dermoid ovarian cyst. Despite those imaging exams we detail a case of a patient where a laparoscopic hysterectomy with bilateral salpingo-oophorectomy and preliminary adhesiolysis has been necessary to establish diagnosis. Among her medical history some previous abdominal surgeries could be the cause of this lesion.
Subject(s)
Laparotomy/adverse effects , Lipoma/etiology , Uterine Neoplasms/etiology , Aged , Female , Humans , Lipoma/diagnosis , Uterine Neoplasms/diagnosisABSTRACT
In most cases, fibrolamellar hepatocellular carcinoma has specific and distinctive histopathological features that distinguish it from hepatocellular carcinoma. Magnetic resonance imaging can provide characteristic features to obtain a diagnosis of this entity. We report a case of fibrolamellar hepatocellular carcinoma with a radiological-pathological correlation in a 37 year-old man with chronic viral hepatitis B without cirrhosis who underwent right hepatectomy.
Subject(s)
Carcinoma, Hepatocellular/etiology , Hepatitis B, Chronic/complications , Liver Neoplasms/etiology , Adult , Carcinoma, Hepatocellular/diagnosis , Humans , Liver Neoplasms/diagnosis , MaleABSTRACT
Pulmonary artery sarcoma is a rare tumor. We present a case of intimal sarcoma arising from right pulmonary artery and left lower pulmonary vein observed in a 44-year-old man with a non-productive cough. Computed tomographic scans and magnetic resonance imaging showing filling defect enhancement contributed early, suggesting the diagnosis of primary vascular tumor, hypothesis confirmed by pathologist findings.