Gal-1 Expression Analysis in the GLIOCAT Multicenter Study: Role as a Prognostic Factor and an Immune-Suppressive Biomarker.

Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM patients. Therefore, new potential treatment targets as well as diagnostic, prognostic, and/or predictive biomarkers are needed to improve outcomes in this population. The ß-galactoside binding protein Galectin-1 (Gal-1) is a protein with a wide range of pro-tumor functions such as proliferation, invasion, angiogenesis, and immune suppression. Here, we evaluated Gal-1 expression by immunohistochemistry in a homogenously treated cohort of GBM (the GLIOCAT project) and correlated its expression with clinical and molecular data. We observed that Gal-1 is a negative prognostic factor in GBM. Interestingly, we observed higher levels of Gal-1 expression in the mesenchymal/classical subtypes compared to the less aggressive proneural subtype. We also observed a Gal-1 expression correlation with immune suppressive signatures of CD4 T-cells and macrophages, as well as with several GBM established biomarkers, including SHC1, PD-L1, PAX2, MEOX2, YKL-40, TCIRG1, YWHAG, OLIG2, SOX2, Ki-67, and SOX11. Moreover, Gal-1 levels were significantly lower in grade 4 IDH-1 mutant astrocytomas, which have a better prognosis. Our results confirm the role of Gal-1 as a prognostic factor and also suggest its value as an immune-suppressive biomarker in GBM.

Glioblastoma TCGA Mesenchymal and IGS 23 Tumors are Identifiable by IHC and have an Immune-phenotype Indicating a Potential Benefit from Immunotherapy.

PURPOSE: Molecular subtype classifications in glioblastoma may detect therapy sensitivities. IHC would potentially allow the identification of molecular subtypes in routine clinical practice. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tumor samples of 124 uniformly treated, newly diagnosed patients with glioblastoma were submitted to RNA sequencing, IHC, and immune-phenotyping to identify differences in molecular subtypes associated with treatment sensitivities. RESULTS: We detected high molecular and IHC overlapping of the The Cancer Genome Atlas (TCGA) mesenchymal subtype with instrinsic glioma subtypes (IGS) cluster 23 and of the TCGA classical subtype with IGS cluster 18. IHC patterns, gene fusion profiles, and immune-phenotypes varied across subtypes. IHC revealed that the TCGA classical subtype was identified by high expression of EGFR and low expression of PTEN, while the mesenchymal subtype was identified by low expression of SOX2 and high expression of two antibodies, SHC1 and TCIRG1, selected on the basis of RNA differential transcriptomic expression. The proneural subtype was identified by frequent positive IDH1 expression and high Olig2 and Ki67 expression. Immune-phenotyping showed that mesenchymal and IGS 23 tumors exhibited a higher positive effector cell score, a higher negative suppressor cell score, and lower levels of immune checkpoint molecules. The cell-type deconvolution analysis revealed that these tumors are highly enriched in M2 macrophages, resting memory CD4+ T cells, and activated dendritic cells, indicating that they may be ideal candidates for immunotherapy, especially with anti-M2 and/or dendritic cell vaccination. CONCLUSIONS: There is a subset of tumors, frequently classified as mesenchymal or IGS cluster 23, that may be identified with IHC and could well be optimal candidates for immunotherapy.

Analysis of sialyl-Lewis x on MUC5AC and MUC1 mucins in pancreatic cancer tissues.

Pancreatic adenocarcinoma (PDAC) lacks efficient biomarkers. Mucins are glycoproteins that can carry aberrant glycosylation in cancer. Our objective was to identify cancer-related glycan epitopes on MUC1 and MUC5AC mucins in PDAC as potential biomarkers. We have analysed the tumour-associated carbohydrate antigens sialyl-Lewis x (SLex) and sialyl-Tn (STn) on MUC1 and MUC5AC in PDAC tissues. The selected cohort for this study consisted of twenty-one PDAC tissues positive for SLex antigen and three normal pancreas specimens as controls. STn expression was shown in 76% of the PDAC tissues. MUC1 and MUC5AC were detected in 90% of PDAC tissues. We performed in situ proximity ligation assay combining antibodies against mucins and glycan epitopes to identify specific mucin glycoforms. MUC1-SLex and MUC5AC-SLex were found in 68% and 84% respectively, of the mucin expressing PDAC tissues, while STn hardly colocalized with any of the evaluated mucins. Further analysis by Western blot of MUC5AC and SLex in eight PDAC tissue lysates showed that six out of eight cases were positive for both markers. Moreover, immunoprecipitation of MUC5AC from positive PDAC tissues and subsequent SLex immunodetection confirmed the presence of SLex on MUC5AC. Altogether, MUC5AC-SLex glycoform is present in PDAC and can be regarded as potential biomarker.

Melanoma primario intramedular: reporte de caso y revisión de la literatura / Primary intramedullary melanoma: Case report and literature review

Una masa intramedular pigmentada es un hallazgo muy raro en la práctica diaria, y supone un reto diagnóstico. Se deben considerar tumores que contienen melanina (ependimoma melanótico y schwannoma melanótico) y los tumores que contienen melanocitos (melanocitoma, melanoma primario, melanoma metastásico). Describimos el caso de un hombre de 47 años con una lesión intramedular a nivel de T7-T8. Las imágenes de resonancia magnética (RM) revelaban una lesión hiperintensa en T1 e hipointensa en T2. El tumor fue resecado parcialmente y tratado con radioterapia adyuvante. La histología y la ausencia de lesiones fuera del sistema nervioso central (SNC) permitieron establecer el diagnóstico de melanoma primario intramedular (MPI). Se realizó una revisión de la literatura de los 26 casos de MPI reportados. Los MPI son tumores extremadamente raros, pero son la causa más frecuente de tumores intramedulares pigmentados. La primera opción de tratamiento es la resección quirúrgica completa, seguida de radioterapia complementaria

A dark pigmented intramedullary mass is very rarely encountered in daily practice, and poses a diagnostic challenge. Several entities have to be considered, including melanin-containing tumours (melanotic ependymoma and melanotic schwannoma) and melanocyte-containing tumours (melanocytoma, primary melanoma and melanoma metastases). The case is presented of a 47 year-old male with a pigmented intramedullary tumour located at T7-T8 level. Magnetic resonance images (MRI) revealed a tumour with hyperintensity on T1 and hypointensity on T2. The tumour was resected partially and treated with adjuvant radiotherapy. The diagnosis of primary intramedullary melanoma (PIM) was established based on histology and the absence of other lesions outside of the CNS. A literature review is presented on the other 26 PIM cases reported. PIM are extremely rare tumours, but are the most frequent cause of pigmented intramedullary tumour. Complete surgical resection is the treatment of choice whenever possible, followed by radiotherapy

[Primary intramedullary melanoma: Case report and literature review]. / Melanoma primario intramedular: reporte de caso y revisión de la literatura.

A dark pigmented intramedullary mass is very rarely encountered in daily practice, and poses a diagnostic challenge. Several entities have to be considered, including melanin-containing tumours (melanotic ependymoma and melanotic schwannoma) and melanocyte-containing tumours (melanocytoma, primary melanoma and melanoma metastases). The case is presented of a 47 year-old male with a pigmented intramedullary tumour located at T7-T8 level. Magnetic resonance images (MRI) revealed a tumour with hyperintensity on T1 and hypointensity on T2. The tumour was resected partially and treated with adjuvant radiotherapy. The diagnosis of primary intramedullary melanoma (PIM) was established based on histology and the absence of other lesions outside of the CNS. A literature review is presented on the other 26 PIM cases reported. PIM are extremely rare tumours, but are the most frequent cause of pigmented intramedullary tumour. Complete surgical resection is the treatment of choice whenever possible, followed by radiotherapy.

Nodular Mucinosis of the Breast in a Male: Reassessment of Diagnostic Criteria and Proposal for Its Classification as a Soft Tissue Tumor in the Myofibroblastoma and Spindle Cell Lipoma Spectrum.

Nodular mucinosis of the breast (NMB) is a rare entity with only a few cases described in the literature, most of them in young girls. All cases are located in the nipple and areolar area and microscopically consist of a multinodular myxoid mesenchymal proliferation. Bands of sclerotic collagen containing preexisting breast ducts and abundant vascularization are other features typical of NMB. No relation to Carney complex has been reported, and an indolent behavior is the rule in all patients. We present a case of NMB occurring in the nipple of a 46-year-old man and analyze the clinicopathological features of the other cases of NMB reported in the English literature, concluding that two of them most likely correspond to trauma-induced cutaneous focal mucinosis of the mammary areola. Finally, we review diagnostic criteria for NMB and elaborate an ontogenetic hypothesis based on both its morphological resemblance to myofibroblastoma and its immunohistochemical profile.

Carcinoma colorrectal en el síndrome de poliposis hiperplásica: caracterización clinicopatológica y molecular / Clinicopathological and morphological characteristics of colorectal carcinoma in hyperplastic polyposis syndrome

El síndrome de poliposis hiperplásica se caracteriza por presentar pólipos hiperplásicos, serrados y tubulares, que frecuentemente se asocian a carcinoma colorrectal. En este estudio de 12 pacientes con este síndrome, con 17 adenocarcinomas colorrectales, se muestra que el 77% de los carcinomas, combinados con adenomas serrados de tamaño superior a 1cm (p=0,002), se localizaron en el colon derecho, que la alteración molecular más frecuente fue la hipermetilación del gen MGMT y que la mutación V600E del gen BRAF se observó sólo en las neoplasias asociadas a un subgrupo de poliposis hiperplásica (p=0,015). Estas alteraciones moleculares corroboran los hallazgos descritos en la «vía serrada» de carcinogénesis del carcinoma colorrectal(AU)

Hyperplastic polyposis syndrome is characterized by the presence of both hyperplastic and serrated polyps as well as tubular adenomas. A high incidence of colorectal carcinoma is associated with this syndrome. The present study of 17 colorectal adenocarcinomas found in 12 patients with this syndrome showed that: (i) 77% of tumours arose in the right colon, especially in association with serrated adenomas larger than 1cm (p=0.002); (ii) MGMT gene hypermethylation was the most frequent molecular alteration, and (iii) the V600E BRAF mutation was only present in those colorectal carcinomas associated with a subgroup of hyperplastic polyposis syndrome (p=0.015). These molecular alterations corroborate the findings described for the role of the serrated pathway in the carcinogenesis of colorectal cancer(AU)

Mujer de 41 años con insuficiencia renal y masa hepática / A 41 year old woman with renal insufficiency and a mass in the liver

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