A high content of intratumoral CD68- and/or CD163-positive macrophages correlates with an adverse outcome in ALK-negative ALCL.

MelanA is a known melanocyte marker and is important in melanoma diagnostics. Some tumours, however, show loss of MelanA expression and may therefore be difficult to distinguish from tumours of mesenchymal origin. Pure spindle-cell melanoma is a rare event, and little is known about its biological background and prognosis. However, morphological changes towards a more mesenchymal shape and cellular dedifferentiation may correlate with reactivation of important developmental programmes (epithelial-to-mesenchymal transition) and disseminative tumour cell properties. Inflammation and CD163+ macrophages have been shown to be important inducers of E-cadherin and cell-to-cell adhesion loss, a pivotal and final event of epithelial-to-mesenchymal transition. In a cohort of 385 patients with melanoma, we located nine tumours with a clonal MelanA expression, defined as a tumour section with a distinct MelanA-negative clone next to a MelanA-positive clone. Interestingly, MelanA-negative clones correlated significantly with an augmented inflammatory response of tumour-infiltrating macrophages (CD163+), complete loss of E-cadherin and a spindle-shaped morphology, irrespective of ulcerated status. These cases show the inflammatory heterogeneity of melanoma, which may have important diagnostic, prognostic and therapeutic implications for the patients. We show that melanomas harbour cell clones that bear strong resemblance to tumour-associated macrophages, a pivotal player in a tumour-supporting microenvironment. Interestingly, this distinct inflammatory phenotype is associated with loss of MelanA expression, the presence of spindle-shape morphology and complete loss of E-cadherin, considered as possible markers of poorly differentiated and more invasive tumour cells.

Objective: Soluble CD163 (sCD163) is a new marker of obesity-related metabolic complications. sCD163 and CD163 mRNA were investigated in relation to the fat distribution at baseline and 12 months after Roux-en-Y gastric bypass (RYGB). Methods: Thirty-one obese subjects (BMI: 42.3 6 4.7 kg/m 2 ) were enrolled. Subcutaneous (SAT) and visceral adipose tissue (VAT) volume were determined by MRI, intrahepatic lipid content (IHL) by MRspectroscopy, and body composition by DXA. Fasting blood samples and adipose tissue samples were obtained, and ELISA and RT-PCR were performed. Results: RYGB-induced weight loss (36 6 11 kg) was accompanied by a significant reduction in sCD163 (2.1 6 0.8 mg/l vs. 1.7 6 0.7 mg/l), SAT, VAT, and IHL (all, P < 0.001). At baseline, sCD163 was associated with VAT (r 5 0.40, P < 0.05) but not with SAT or IHL. Moreover, CD163 mRNA was significantly upregulated in VAT compared with SAT at baseline (P < 0.05) and significantly downregulated in SAT after RYGB (P < 0.001). DsCD163 was significantly associated with DIHL after RYGB compared with baseline (r 5 0.40, P < 0.05). Conclusions: RYGB-induced weight loss results in a reduction of sCD163 and CD163 mRNA. The association between DsCD163 and DIHL may reflect a reduction in sCD163-producing Kupffer cells in the liver. Moreover, sCD163 may be a marker of "unhealthy" fat distribution in obese subjects.

It has been suggested that embryogenic properties of migratory cells are reactivated during wound healing and metastasis in adults. This might explain the association between wound-induced inflammation and poor survival in patients with ulcerated melanoma. Linking inflammation with a migratory phenotype, we characterize the infiltration of innate inflammatory cells, loss of cell-to-cell adhesion (E-cadherin), factors associated with extracellular matrix degradation [matrix metalloproteinase-9 (MMP-9), and neutrophil elastase (NE)], and spindle-shaped cell morphology, between ulcerated (n = 179) and nonulcerated (n = 206) melanoma. In addition, the presence of "extravascular migratory metastasis" (angiotropism) and tumor-vessel density were evaluated as important factors for tumor cell dispersal in ulcerated melanoma. We showed a correlation between expression of the granulocyte marker cd66b+ and the expression of NE and MMP-9, reflecting activated neutrophils. Ulcerated melanoma correlated with a low global E-cadherin score (P = 0.041) and weak-spot score (P = 0.0004). Thus, 28% of the nonulcerated, 42% of the minimally/moderately ulcerated melanoma, and 53% of the excessively ulcerated melanoma presented low scores as opposed to a high E-cadherin score. In addition, the presence of ulceration was correlated with angiotropism (P < 0.0001) and spindle-shaped morphology (P = 0.021). There were no differences in MMP-9 expression or intratumoral vessel density between the ulcerated and nonulcerated group. In conclusion, expression of migratory cell properties showed a highly heterogeneous pattern, which was associated with ulcerated areas and inflammatory cells, in general and with neutrophils in particular. We, therefore, suggest that wound-associated inflammation may be involved in the induction of migratory cell transition and tumor cell dispersal in ulcerated melanoma.

Metabolic syndrome rather than lipodystrophy was associated with major unfavorable abdominal subcutaneous adipose tissue changes. In a clinical setting, it may be more relevant to focus on metabolic syndrome diagnosis in HIV-infected patients on cART with regards to adipose tissue dysfunction and risk of cardiometabolic complications.