CANCER DU SEIN ET CHIMIOTHERAPIE NEOADJUVANTE (EVALUATION DE LA REPONSE HISTOPATHOLOGIQUE ET DETERMINATION DE FACTEURS PREDICTIFS ET PRONOSTIQUES)

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Mutation of Tp53 in a Patient with Aggressive Central Nervous System Solitary Fibrous Tumor/Hemangiopericytoma

International audienceIntroduction: Central Nervous System (CNS) Solitary Fibrous Tumor (SFT) / Hemangiopericytoma (HPC) is a fibroblastic mesenchymal tumor of the meninges that accounts for < 1% of intracranial tumours. The natural history of CNS SFT / HPC is characterized by a high rate of local (60%) and distant (20%) failure following gross total resection (GTR), and treatment options are limited. The identification of new genomic markers could be of interest to improve the understanding and management of CNS SFT / HPC. We present the results of a search for molecular alterations by next-generation sequencing (NGS) in a patient diagnosed with CNS SFT / HPC who experienced rapid distant failure. Case Description: A 64-year-old Caucasian man was diagnosed with a right hemisphere extra-axial frontal tumor after being referred for persistent headaches in October 2017. The patient underwent surgical resection followed by adjuvant radiation therapy of the operative cavity. A diagnosis of grade III HPC of the CNS was established. A diffuse metastatic recurrence with multiple bone lesions occurred rapidly after the initiation of radiation therapy. In July 2018, a CT-guided biopsy of the left iliac crest confirmed a highly proliferative metastatic recurrence and a FoundationOne CDx TM test was performed, which showed a somatic mutation of the tumor suppressor gene TP53 (Tumor Protein p53) (R175H). The microsatellite status was stable and the Tumor Mutational Burden (TMB) was low (1 Muts/Mb). A massive disease evolution of the disease occurred in September 2018. The patient died in November 2018 after neurological decline. Conclusion: This case report shows that an anatomopathological examination alone is insufficient to correctly classify these rare tumors and predict their aggressiveness. In this case report, the somatic mutation of TP53 (R175H) was associated with a very poor prognosis (survival of 13 months). Further studies including systematic NGS of CNS SFT / HPC are warranted to investigate the role of TP53 in prognostic assessment to adapt future treatment strategies

Novel Therapeutic Options for Solitary Fibrous Tumor: Antiangiogenic Therapy and Beyond

International audienceSFT is an ultrarare mesenchymal ubiquitous tumor, with an incidence rate <1 case/million people/year. The fifth WHO classification published in April 2020 subdivided SFT into three categories: benign (locally aggressive), NOS (rarely metastasizing), and malignant. Recurrence can occur in up to 10–40% of localized SFTs, and several risk stratification models have been proposed to predict the individual risk of metastatic relapse. The Demicco model is the most widely used and is based on age at presentation, tumor size, and mitotic count. Total en bloc resection is the standard treatment of patients with a localized SFT; in case of advanced disease, the clinical efficacy of conventional chemotherapy remains poor. In this review, we discuss new insights into the biology and the treatment of patients with SFT. NAB2–STAT6 oncogenic fusion, which is the pathognomonic hallmark of SFT, is supposedly involved in the overexpression of vascular endothelial growth factor (VEGF). These specific biological features encouraged the successful assessment of antiangiogenic drugs. Overall, antiangiogenic therapies showed a significant activity toward SFT in the advanced/metastatic setting. Nevertheless, these promising results warrant additional investigation to be validated, including randomized phase III trials and biological translational analysis, to understand and predict mechanisms of efficacy and resistance. While the therapeutic potential of immunotherapy remains elusive, the use of antiangiogenics as first-line treatment should be considered

Giant mature ovarian cystic teratoma including more than 300 teeth

International audiencePreoperative diagnosis of malignant tumors arising from mature cystic teratoma (MCT) of the ovary is not easy; malignant tumors are mostly diagnosed only postoperatively. Tumor size, serum tumor markers, and patient age have been proposed as risk factors for malignancy. This article reports a rare case of a giant, benign MCT of the ovary in a young woman (25 years old). It had a very large size (320 x 270 x 185 mm, 10 kg), a great number of teeth (> 300), and preoperative serum level of tumor markers were elevated (CA125, 875 U/mL(-1); CA19-9, 2087 U/mL(-1); CEA, 5.1 ng/mL(-1); AFP, 23.3 ng/mL(-1); SCC, 20.7 ng/mL(-1)). Based on clinical and laboratory data, tumor markers and tumor size when used alone or in combination do not appear to be useful in making a differential diagnosis between MCT and squamous cell carcinoma arising from MCT. However, radiologically detectable, well-differentiated teeth may be indicative of benignity

Dietary fat without body weight gain increases in vivo MCF-7 human breast cancer cell growth and decreases natural killer cell cytotoxicity

High-calorie (HC) diet contributes to the increased incidence of obesity, which is a risk factor for breast cancer in postmenopausal women, and in particular for estrogen receptor (ER) positive tumors. This study investigated whether an HC diet increases human ER-positive breast cancer progression and modulates natural killer (NK) cell functions. Four-week-old female BALB/c athymic nude mice were fed a HC diet (5320 kcal/kg) or standard calorie diet (SC, 2820 kcal/kg) for 6 mo. After 5 mo, the mice were randomly implanted with MCF-7 breast cancer cells (SCT and HCT) or received an isovolumic injection (SC and HC) in both inguinal fat pads. Tumor growth was greater in the HCT group than in the SC group without change in body weight. The HC diet decreased the tumor expression of genes involved in the citrate cycle and in adiponectin and lipid metabolism but increased that of genes controlling glycolysis and angiogenesis. The tumor expression level of Ki67 was increased while that of the cleaved caspase 3 and the ER-beta and progesterone receptors was reduced. Tumor development in response to the HC diet was associated with smaller numbers and lower cytotoxicity of splenic NK cells. These results indicate that an HC diet without body weight gain increases ER-positive breast cancer cell proliferation and reduces tumor apoptosis. The underlying mechanisms might involve a downexpression of tumor hormonal receptor and reduced NK cell functions, and might also result in the regulation of genes involved in several cellular functions. (c) 2013 Wiley Periodicals, Inc

Hibernoma: a clinical model for exploring the role of brown adipose tissue in the regulation of body weight?

Context: Hibernoma is a rare benign tumor histologically similar to brown adipose tissue. Some studies reported weight loss in patients with this tumor; however, the mechanisms have never been investigated. Objective: The purpose of this study is to explore the impact of hibernoma resection on the whole-body metabolism. Patient and Methods: A 68-year-old woman was examined after a weight loss of 10 kg in 6 months. Body composition, food intake, physical activity, blood levels of thyroid hormones, and lipid profile were assessed before surgery and during 1 year after surgery. The patient's resting energy expenditure (REE) over time was compared to a control group of 18 matched healthy volunteers. Results: Within 1 year after hibernoma resection, the patient gained 15 kg of body weight. This was associated with fat mass gain (+41%), mainly in the abdominal region (+48%). The patient also developed hepatic nonalcoholic steatosis, mild hypertriglyceridemia, and reduced levels of high-density lipoproteins. REE increased during the dynamic phase of weight gain, compared to the presurgery measurement, and returned to baseline after 1 year. Food intake was increased by 37.5% 6 weeks after resection of the hibernoma and returned to baseline values within 6 months. Conclusions: In our study conditions, hibernoma did not alter REE, but weight gain did. Specific physical activities and dietetic follow-ups are suggested for those patients to prevent excess fat mass gain and metabolic disorders after hibernoma resection. More studies should focus on hibernoma mechanisms inducing weight loss. Affiliation

New insight into the role of ANXA1 in melanoma progression: involvement of stromal expression in dissemination.

International audienceANXA1, first described in the context of inflammation, appears to be deregulated in many cancers and increased in melanomas compared with melanocytes. To date, few studies have investigated the role of ANXA1 in melanoma progression. Furthermore, this protein is expressed by various cell types, including immune and endothelial cells. We therefore analyzed the specific roles of ANXA1 using melanoma and stromal cells in two human cell lines (A375-MA2 and SK-MEL-28) in vitro and in Anxa1 null C57Bl6/J mice bearing B16Bl6 tumors. We report decreased proliferation in both ANXA1 siRNA A375-MA2 and SK-MEL-28, but cell-dependent effects of ANXA1 in migration in vitro. However, we also observed a significant decrease of B16Bl6 tumor growth associated with a reduction of Ki-67 positive cells in Anxa1 null mice compared with wild-type mice. Interestingly, we also found a significant reduction of spontaneous metastases, which can be attributed to decreased angiogenesis concomitantly with greater immune cell presence in the Anxa1 null stromal context. This study highlights the pejorative role of ANXA1 in both tumor and stromal cells in melanoma, due to its involvement in proliferation and angiogenesis

TIP60: an actor in acetylation of H3K4 and tumor development in breast cancer

International audienceThe acetyltransferase TIP60 is reported to be downregulated in several cancers, in particular breast cancer, but the molecular mechanisms resulting from its alteration are still unclear

[¹²³I]ICF01012 melanoma imaging and [¹³¹I]ICF01012 dosimetry allow adapted internal targeted radiotherapy in preclinical melanoma models.

International audienceMelanin-targeting radiotracers are interesting tools for imaging and treatment of pigmented melanoma metastases. However, variation of the pigment concentration may alter the efficiency of such targeting