b858412f98f76f66eafca417c3ee5790 pmc_10216449.pdf f8449dbd8d42678b314b0adf696814d2e5704085 pmc_10216449.pdf a4b16eb8a31da4afd58986ee31805e7e5ffd09c7925bc65077fc1df1e7835bc9 pmc_10216449.pdf Title: P53 in Penile Squamous Cell Carcinoma: A Pattern-Based Immunohistochemical Framework with Molecular Correlation Subject: p53 immunohistochemistry (IHC) has been proposed as a surrogate for TP53 mutations in penile squamous cell carcinomas (PSCC). We aimed to evaluate the performance of a pattern-based evaluation of p53 IHC in PSCC. Human papilloma virus (HPV) DNA testing, p16 and p53 IHC, and whole exome sequencing were performed in a series of 40 PSCC. p53 IHC was evaluated following a pattern-based framework and conventional p53 IHC evaluation. Out of 40 PSCC, 12 (30.0%) were HPV-associated, and 28 (70.0%) were HPV-independent. The agreement between the p53 IHC pattern-based evaluation and TP53 mutational status was almost perfect (k = 0.85). The sensitivity and accuracy of the pattern-based framework for identifying TP53 mutations were 95.5% and 92.5%, respectively, which were higher than the values of conventional p53 IHC interpretation (54.5% and 70.0%, respectively), whereas the specificity was the same (88.9%). In conclusions, the pattern-based framework improves the accuracy of detecting TP53 mutations in PSCC compared to the classical p53 IHC evaluation. Keywords: p53 immunohistochemistry; TP53 mutations; penile squamous cell carcinoma; surrogate marker; pattern-based framework Author: Isabel Trias, Adela Saco, Lorena Marimon, Ricardo López del Campo, Carolina Manzotti, Oriol Ordi, Marta del Pino, Francisco M. Pérez, Naiara Vega, Silvia Alós, Antonio Martínez, Leonardo Rodriguez-Carunchio, Oscar Reig, Pedro Jares, Cristina Teixido, Tarek Ajami, Juan Manuel Corral-Molina, Ferran Algaba, María J. Ribal, Inmaculada Ribera-Cortada and Natalia Rakislova Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu May 11 12:31:42 2023 CEST ModDate: Thu May 11 12:36:10 2023 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 18263148 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- XWOCXD+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 DPXZZG+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 BUPMPU+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 NKPFZL+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 HFUITD+VnURWPalladioL Type 1 Custom yes yes no 28 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 47 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 72 0 VYVZGZ+CMSY10 Type 1 Builtin yes yes no 79 0 KCKNEM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 86 0 KCKNEO+PalatinoLinotype TrueType WinAnsi yes yes no 89 0 KCKNFA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 92 0 FIVVOC+URWPalladioL-BoldItal Type 1 Custom yes yes no 133 0 MDIKPC+CMBSY10 Type 1 Builtin yes yes no 137 0 KCKNEM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 147 0 KCKNEO+PalatinoLinotype TrueType WinAnsi yes yes no 150 0 KCKNFA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 153 0 KCMKGA+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 156 0 KCKNEM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 173 0 KCKNEO+PalatinoLinotype TrueType WinAnsi yes yes no 176 0 KCKNFA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 179 0 KCKNEM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 187 0 KCKNEO+PalatinoLinotype TrueType WinAnsi yes yes no 190 0 KCKNFA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 193 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-07-25 02:29:59 CEST RepresentationInformation: pmc_10216449.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-07-20 02:26:51 CEST Size: 18263148 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 391 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Material and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Case Selection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Histological Revision Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: HPV Testing, p16 IHC, and Criteria for Classifying a Tumour as HPV-Associated or HPV-Independent Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: p53 IHC Staining and Evaluation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Whole Exome Sequencing and Bioinformatic Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Attribution of TP53 Mutational Status Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Children: Item: Title: Cases Included in the Study and Association with HPV Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Characteristics of the Overall Series Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: TP53 Mutations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Agreement between p53 IHC and TP53 Mutational Status and Interobserver Agreement Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: p53 IHC Patterns and TP53 Status in HPV-Associated PSCC Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: p53 IHC Patterns and TP53 Status in HPV-Independent PSCC Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Info: Title: P53 in Penile Squamous Cell Carcinoma: A Pattern-Based Immunohistochemical Framework with Molecular Correlation Author: Isabel Trias, Adela Saco, Lorena Marimon, Ricardo López del Campo, Carolina Manzotti, Oriol Ordi, Marta del Pino, Francisco M. Pérez, Naiara Vega, Silvia Alós, Antonio Martínez, Leonardo Rodriguez-Carunchio, Oscar Reig, Pedro Jares, Cristina Teixido, Tarek Ajami, Juan Manuel Corral-Molina, Ferran Algaba, María J. Ribal, Inmaculada Ribera-Cortada and Natalia Rakislova Subject: p53 immunohistochemistry (IHC) has been proposed as a surrogate for TP53 mutations in penile squamous cell carcinomas (PSCC). We aimed to evaluate the performance of a pattern-based evaluation of p53 IHC in PSCC. Human papilloma virus (HPV) DNA testing, p16 and p53 IHC, and whole exome sequencing were performed in a series of 40 PSCC. p53 IHC was evaluated following a pattern-based framework and conventional p53 IHC evaluation. Out of 40 PSCC, 12 (30.0%) were HPV-associated, and 28 (70.0%) were HPV-independent. The agreement between the p53 IHC pattern-based evaluation and TP53 mutational status was almost perfect (k = 0.85). The sensitivity and accuracy of the pattern-based framework for identifying TP53 mutations were 95.5% and 92.5%, respectively, which were higher than the values of conventional p53 IHC interpretation (54.5% and 70.0%, respectively), whereas the specificity was the same (88.9%). In conclusions, the pattern-based framework improves the accuracy of detecting TP53 mutations in PSCC compared to the classical p53 IHC evaluation. 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