ABSTRACT
(1) Background: While obesity is a known independent risk factor in the development of melanoma, there is no consensus on its influence on melanoma prognosis. (2) Methods: In a monocentric retrospective study, data was collected from patients who underwent sentinel lymph node (SLN) biopsy for stage IB-IIC melanoma between 2013 and 2018. Patients were divided into groups according to their body mass index (BMI). The association between BMI and melanoma features, as well as the risk factors for metastases in SLN were examined. (3) Results: Of the 1001 patients, 336 had normal weight (BMI < 25), 402 were overweight (BMI >= 25 and <30), 173 obese (BMI >= 30 and <35) and 90 extremely obese (BMI >= 35). Overweightness and obesity were associated with higher tumor thicknesses at time of diagnosis. Ulceration was not influenced by the patient's weight. Metastases in sentinel lymph node was almost twice more likely in extremely obese patients than in normal weight patients. Independent risk factors for metastases in SLN in our study were tumor thickness, ulceration, and BMI > 35. (4) Conclusions: This is the first study to show higher metastases rates in high-BMI patients with melanoma, raising important questions regarding the screening and treatment of this specific patient population.
ABSTRACT
Cdkn1a, which encodes p21, functions as a major route for p53-mediated cell-cycle arrest. However, the consequence of Cdkn1a gene dosage on tumor suppression has not been systematically investigated. Here, we employed BAC transgenesis to generate a Cdkn1aSUPER mouse, which harbors an additional Cdkn1a allele within its natural genomic context. We show that these mice display enhanced cell-cycle arrest and reduced apoptosis in response to genotoxic stress. Furthermore, using a chemically induced skin cancer model and an autochthonous Kras-driven lung adenocarcinoma model, we show that Cdkn1aSUPER mice display a cancer protection phenotype that is indistinguishable from that observed in Tp53SUPER animals. Moreover, we demonstrate that Tp53 and Cdkn1a cooperate in mediating cancer resistance, using a chemically induced fibrosarcoma model. Overall, our Cdkn1aSUPER allele enabled us to assess the contribution of Cdkn1a to Tp53-mediated tumor suppression.
