Association of HLA-DPA1 Expression with Clinical and Biological Characteristics of Uniformly Mana... more Association of HLA-DPA1 Expression with Clinical and Biological Characteristics of Uniformly Managed Pediatric Adrenocortical Carcinoma
Supplementary Fig 1. Discriminating gap size (DGS) criterion shows a gap in the distribution of t... more Supplementary Fig 1. Discriminating gap size (DGS) criterion shows a gap in the distribution of the expression of MHC class II expression in the IPACTR cohort. Supplementary Fig 2. Immunohistochemical analysis of CD3, CD4, and CD8 expression.
Discriminating gap size (DGS) criterion shows a gap in the distribution of the expression of MHC ... more Discriminating gap size (DGS) criterion shows a gap in the distribution of the expression of MHC class II expression in the IPACTR cohort. Each panel plots the rank of expression value in the cohort on the y-axis and the positive quantile transformation (PQT) value on the x-axis. Solid blue circles indicate adrenocortical carcinomas, open red circles indicate adrenocortical adenomas, and black X-marks indicate undetermined histology. In each plot, the gray rectangle highlights the large gap in the distribution that discriminates adenomas from carcinomas which was identified by the DGS criterion.
Immunohistochemical analysis of CD3, CD4, and CD8 expression. Row: a) adenoma; b) stage I carcino... more Immunohistochemical analysis of CD3, CD4, and CD8 expression. Row: a) adenoma; b) stage I carcinoma; and c) stage III carcinoma. Note that cells with short processes are dimly positive for CD4, consistent with macrophages; cells with long process are also dimly positive for CD4, consistent with dendritic cells (Magnification, 100x; inset, 400x).
The TP53-R337H founder mutation exists at a high frequency throughout southern Brazil and represe... more The TP53-R337H founder mutation exists at a high frequency throughout southern Brazil and represents one of the most common germline TP53 mutations reported to date. It was identified in pediatric adrenocortical tumors in families with a low incidence of cancer. The R337H mutation has since been found in association with early-onset breast cancers and Li–Fraumeni syndrome (LFS). To study this variability in tumor susceptibility, we generated a knockin mutant p53 mouse model (R334H). Endogenous murine p53-R334H protein was naturally expressed at high levels in multiple tissues and was functionally compromised in a tissue- and stress-specific manner. Mutant p53-R334H mice developed tumors with long latency and incomplete penetrance, consistent with many human carriers being at a low but elevated risk for cancer. These findings suggest the involvement of additional cooperating genetic alterations when TP53-R337H occurs in the context of LFS, which has important implications for genetic counseling and long-term clinical follow-up.Significance:A p53-R334H knockin mouse serves as an important model for studying the most common inherited germline TP53 mutation (R337H) that is associated with variable tumor susceptibility.
Association of HLA-DPA1 Expression with Clinical and Biological Characteristics of Uniformly Mana... more Association of HLA-DPA1 Expression with Clinical and Biological Characteristics of Uniformly Managed Pediatric Adrenocortical Carcinoma
Supplementary Fig 1. Discriminating gap size (DGS) criterion shows a gap in the distribution of t... more Supplementary Fig 1. Discriminating gap size (DGS) criterion shows a gap in the distribution of the expression of MHC class II expression in the IPACTR cohort. Supplementary Fig 2. Immunohistochemical analysis of CD3, CD4, and CD8 expression.
Discriminating gap size (DGS) criterion shows a gap in the distribution of the expression of MHC ... more Discriminating gap size (DGS) criterion shows a gap in the distribution of the expression of MHC class II expression in the IPACTR cohort. Each panel plots the rank of expression value in the cohort on the y-axis and the positive quantile transformation (PQT) value on the x-axis. Solid blue circles indicate adrenocortical carcinomas, open red circles indicate adrenocortical adenomas, and black X-marks indicate undetermined histology. In each plot, the gray rectangle highlights the large gap in the distribution that discriminates adenomas from carcinomas which was identified by the DGS criterion.
Immunohistochemical analysis of CD3, CD4, and CD8 expression. Row: a) adenoma; b) stage I carcino... more Immunohistochemical analysis of CD3, CD4, and CD8 expression. Row: a) adenoma; b) stage I carcinoma; and c) stage III carcinoma. Note that cells with short processes are dimly positive for CD4, consistent with macrophages; cells with long process are also dimly positive for CD4, consistent with dendritic cells (Magnification, 100x; inset, 400x).
The TP53-R337H founder mutation exists at a high frequency throughout southern Brazil and represe... more The TP53-R337H founder mutation exists at a high frequency throughout southern Brazil and represents one of the most common germline TP53 mutations reported to date. It was identified in pediatric adrenocortical tumors in families with a low incidence of cancer. The R337H mutation has since been found in association with early-onset breast cancers and Li–Fraumeni syndrome (LFS). To study this variability in tumor susceptibility, we generated a knockin mutant p53 mouse model (R334H). Endogenous murine p53-R334H protein was naturally expressed at high levels in multiple tissues and was functionally compromised in a tissue- and stress-specific manner. Mutant p53-R334H mice developed tumors with long latency and incomplete penetrance, consistent with many human carriers being at a low but elevated risk for cancer. These findings suggest the involvement of additional cooperating genetic alterations when TP53-R337H occurs in the context of LFS, which has important implications for genetic counseling and long-term clinical follow-up.Significance:A p53-R334H knockin mouse serves as an important model for studying the most common inherited germline TP53 mutation (R337H) that is associated with variable tumor susceptibility.
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Papers by Raul Ribeiro