PRAME (PReferentially expressed Antigen in MElanoma) is a tumor-associated antigen that was recently found to be expressed by malignant melanocytic lesions but not by benign ones, thus resulting useful in this diagnostic field. PRAME could also be expressed by some normal tissues and nonmelanocytic tumors, suggesting as caution should be adopted to use PRAME as a "pan-melanoma" marker for the differential diagnosis with other malignant tumors. Until now, PRAME expression was exclusively investigated through single staining with a monoclonal antibody targeting PRAME and with double staining for Melan A/PRAME found to be useful in specific diagnostic sets. Herein, we studied the expression of PRAME in 40 melanocytic lesions and 23 nonmelanocytic ones using PRAME, Melan A/ PRAME, and novel double staining for HMB45/PRAME. Although our results need to be validated, they support the adoption of HMB45/PRAME, alone or in combination with PRAME and Melan A/PRAME, as a helpful marker in the diagnosis of melanocytic neoplasms with a high concordance rate between primary melanoma and corresponding metastases.
Aims Primary mixed liver cancers (PLCs), combined hepatocellular‐cholangiocellular (cHCC‐CC) and intermediate‐cell carcinomas are rare tumours characterised by different molecular mechanisms. Nestin is a marker of progenitor cells with a promising application in human tumours. The aims of the present paper are (i) to determine the expression of Nestin in mixed PLCs; and (ii) to correlate the PLC immunoprofile with the gene expression in each tumour component. Methods and results We selected 28 mixed PLCs, 13 (46.4%) cHCC‐CC and 15 (53.6%) intermediate‐cell carcinomas. The immunohistochemistry panel consisted of keratin 7, keratin 19, CD56 and Nestin. Next‐generation sequencing analysis was performed on 17 cases (27 specimens) using a multi‐gene custom panel. The differentiated HCC and CC components of cHCC‐CC were negative for Nestin in all cases. The intermediate areas of cHCC‐CC were immunoreactive for Nestin in 92.3% of cases, for CD56 in 76.9% and for K7/K19 in all cases. The immunoprofile of the intermediate‐cell carcinomas showed 73.3% of cases positive for Nestin and 66.7% for CD56. TP53 and TERT were the most frequently mutated genes (31.3% and 17.6% of samples, respectively). Mutations were also found in IDH1, IDH2, PIK3CA and NRAS genes. Intermediate and HCC areas of cHCC‐CC seemed to share the same mutational profile, and both harboured different mutations than the CC component. Conclusions According to our preliminary data, Nestin was not expressed by hepatocellular or cholangiocellular‐cell components, but was expressed by most of the intermediate cells in PLCs, and therefore could be considered in the differential diagnosis of PLCs, together with mutational profile.
The collaborative Cancer Genome Atlas (TCGA) project identified four distinct prognostic groups of endometrial carcinoma (EC) based on molecular alterations: (i) the ultramutated subtype that encompasses POLE mutated (POLE) cases; (ii) the hypermutated subtype, characterized by MisMatch Repair deficiency (MMRd); (iii) the copy-number high subtype, with p53 abnormal/mutated features (p53abn); (iv) the copy-number low subtype, known as No Specific Molecular Profile (NSMP). Although the prognostic value of TCGA molecular classification, NSMP carcinomas present a wide variability in molecular alterations and biological aggressiveness. This study aims to investigate the impact of ARID1A and CTNNB1/β-catenin alterations by targeted Next-generation sequencing (NGS) and immunohistochemistry (IHC) in a consecutive series of 125 molecularly classified ECs. NGS and IHC were used to assign surrogate TCGA groups and to identify molecular alterations of multiple target genes including POLE, PTEN, ARID1A, CTNNB1, TP53. Associations with clinicopathologic parameters, molecular subtypes, and outcomes identified NSMP category as the most heterogeneous group in terms of clinicopathologic features and outcome. Integration of surrogate TCGA molecular classification with ARID1A and β-catenin analysis showed NSMP cases with ARID1A mutation characterized by the worst outcome with early recurrence, while NSMP tumors with ARID1A wild-type and β-catenin alteration had indolent clinicopathologic features and no recurrence. This study indicates how the identification of ARID1A and β-catenin alterations in EC represents a simple and effective way to characterize NSMP tumor aggressiveness and metastatic potential.
Objectives Preferentially expressed antigen in melanoma (PRAME) has a key role in regulating pluripotency of primordial germ cells and in the development of germ cell tumors of the testis (GCTT). However, its immunohistochemical expression in normal testes and its neoplastic counterpart remain largely unknown. Methods We retrospectively investigated the expression of PRAME in 26 cases of GCTT, 21 cases of germ cell neoplasia in situ (GCNIS), and 17 cases of uninvolved background testes. Results We found that PRAME was expressed more strongly by seminomatous rather than nonseminomatous GCTT (P = .000) and by pure seminoma rather than the seminoma component of seminomatous/nonseminomatous GCTT (P = .025). In addition, GCNIS and uninvolved background testes displayed high levels of PRAME expression. Conclusions PRAME is an additional marker for the differential diagnosis of GCTT and could play a key role in the transition from seminomatous to nonseminomatous GCTT.
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