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Conjunctival melanoma (CM) iss a rare and aggressive tumour that is increasing in frequency. The prognostic value of PD-L1 expression, alone or in combination with CD8 and PD-1 expression and the BRAF and NRAS status, has not been determined in CM to date. We evaluated the expression of PD-L1, CD8, PD-1 in CM and investigated whether there was an association between the expression of these markers and the BRAF and NRAS molecular profile as well as some clinico-pathological criteria. A total of sixty-five CM were assessed for PD-L1, PD-1, and CD8 expression by immunohistochemistry (IHC) and for BRAF and NRAS genomic alterations using molecular biology techniques and anti-BRAF and anti-NRAS antibodies. PD-L1 expression in tumour cells (TC) was very low or absent but detected in tumour-infiltrating immune cells (IC). A correlation was observed between the expression of PD-L1, CD8, and PD-1 in IC. No correlation between PD-L1 expression (in tumour and/or immune cells) and BRAF or NRAS mutations was observed. PD-L1 expression in IC correlated with a higher pTNM stage and PD-L1 expression in TC with worse disease-specific survival. PD-L1 expression is a potential prognostic biomarker that correlates with poor prognosis in CM patients.

Aims Distinction between primary cutaneous follicular lymphoma ( PCFL) and primary cutaneous marginal zone lymphoma ( PCMZL) is challenging, as clear-cut immunophenotypical and cytogenetic criteria to segregate both entities are lacking. Methods and results To characterize PCFL and PCMZL more clearly and to define criteria helpful for the differential diagnosis, we compared expression of immunohistochemical markers [ LIM-only transcription factor 2 ( LMO2), human germinal centre-associated lymphoma ( HGAL), stathmin 1 ( STMN1), activation-induced cytidine deaminase ( AID), myeloid cell nuclear differentiation antigen ( MNDA)] and the presence of cytogenetic abnormalities described previously in nodal follicular lymphoma [B cell lymphoma 2 ( BCL2) and BCL6 breaks, 1p36 chromosomal region deletion (del 1p36)] in a series of 48 cutaneous follicular and marginal zone lymphomas [cutaneous follicular lymphoma ( CFL) and cutaneous marginal zone lymphoma ( CMZL)]. Immunostaining for STMN1, LMO2, HGAL and AID allowed the distinction between CFL and CMZL, and STMN1 was the most sensitive marker (100% CFL, 0% CMZL). LMO2, HGAL and AID were positive in 93.2%, 82.1% and 86.2% CFL (all CMZL-negative). MNDA was expressed in both entities without significant difference (10.3% CFL, 30.8% CMZL, P = 0.18). BCL2, BCL6 breaks and the del 1p36 were present in 16.7%, 10.7% and 18.5% CFL and no CMZL. Finally, three and 29 CFL were reclassified as secondary cutaneous follicular lymphomas ( SCFL) and PCFL without significant differences concerning phenotypical and cytogenetic features. BCL2, BCL6 breaks and the del 1p36 were present in 11.1%, 8% and 16.7% PCFL and did not impact the prognosis. Conclusion LMO2, HGAL, STMN1 and AID, but not MNDA, are discriminant for the recognition between CFL and CMZL. BCL2, BCL6 rearrangements and the del 1p36 have a role in the pathogenesis of PCFL, the latest being the most common alteration. [ABSTRACT FROM AUTHOR]

Hypertrophic scars (HTS) are characterized by excessive amount of collagen deposition and principally occur following burn injuries or surgeries. In absence of effective treatments, the use of mesenchymal stem/stromal cells, which have been shown to attenuate fibrosis in various applications, seems of interest. The objectives of the present study were therefore to evaluate the effect of human adipose tissue-derived mesenchymal stem cells (hASC) on a pre-existing HTS in a humanized skin graft model in Nude mice and to compare the efficacy of hASCs versus stromal vascular fraction (SVF). We found that injection of SVF or hASCs resulted in an attenuation of HTS as noticed after clinical evaluation of skin thickness, which was associated with lower total collagen contents in the skins of treated mice and a reduced dermis thickness after histological analysis. Although both SVF and hASCs were able to significantly reduce the clinical and histological parameters of HTS, hASCs appeared to be more efficient than SVF. The therapeutic effect of hASCs was attributed to higher expression of TGFβ3 and HGF, which are important anti-fibrotic mediators, and to higher levels of MMP-2 and MMP-2/TIMP-2 ratio, which reflect the remodelling activity responsible for fibrosis resorption. These results demonstrated the therapeutic potential of hASCs for clinical applications of hypertrophic scarring. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancers (CRC) with brain metastases (BM) are scarcely described. The main objective of this study was to determine the molecular profile of CRC with BM. Methods: We included 82 CRC patients with BM. KRAS, NRAS, BRAF and mismatch repair (MMR) status were investigated on primary tumors (n = 82) and BM (n = 38). ALK, ROS1, cMET, HER-2, PD-1, PD-L1, CD3 and CD8 status were evaluated by immunohistochemistry, and when recommended, by fluorescence in situ hybridization. Results: In primary tumors, KRAS, NRAS and BRAF mutations were observed in 56%, 6%, and 6% of cases, respectively. No ROS1, ALK and cMET rearrangement was detected. Only one tumor presented HER-2 amplification. Molecular profiles were mostly concordant between BM and paired primary tumors, except for 9% of discordances for RAS mutation. CD3, CD8, PD-1 and PD-L1 expressions presented some discordance between primary tumors and BM. In multivariate analysis, multiple BM, lung metastases and PD-L1+ tumor were predictive of poor overall survival. Conclusions: CRCs with BM are associated with high frequency of RAS mutations and significant discordance for RAS mutational status between BM and paired primary tumors. Multiple BM, lung metastases and PD-L1+ have been identified as prognostic factors and can guide therapeutic decisions for CRC patients with BM. [ABSTRACT FROM AUTHOR]