PathobiologyPub Date : 2025-05-28DOI: 10.1159/000546206
Szintia Almási, Tibor Krenács, László Krenács, Gábor Cserni
{"title":"Galectin-1 Expression in Breast Cancer Stroma: Prognostic Value in Triple-Negative Breast Cancer.","authors":"Szintia Almási, Tibor Krenács, László Krenács, Gábor Cserni","doi":"10.1159/000546206","DOIUrl":"10.1159/000546206","url":null,"abstract":"<p><strong>Introduction: </strong>Galectin-1 is a lectin with immunosuppressive effect in different solid tumors. We investigated galectin-1 expression in triple-negative breast cancer (TNBC) to determine its prognostic value.</p><p><strong>Methods: </strong>We examined 95 TNBC surgical samples in tissue microarrays with galectin-1 immunohistochemistry (intensity and percentage of staining) and looked for influences on overall and progression-free survivals (PFSs) with the help of Kaplan-Meier estimates. Univariable and multivariable Cox regressions were also analyzed.</p><p><strong>Results: </strong>According to Kaplan-Meier curves, a significantly worse overall survival (OS) was found for TNBC patients showing intense or ≥50% galectin-1 stromal interface staining versus those lacking it. Cox regression analyses suggested that galectin-1 expression was an independent prognosticator in TNBC. According to the quantity of stromal tumor-infiltrating lymphocytes (sTILs), significant survival differences depending on galectin-1 status were only seen in the low sTILs (<30%) subset. Multivariable analysis suggested that galectin-1 expression was an independent prognosticator for PFS.</p><p><strong>Discussion: </strong>The immunosuppressive effects of galectin-1 forming a shield around tumor nests may form an immune escape mechanism and can explain the worse OS and PFS we found in TNBC. Owing to the exploratory nature of the study, the results need confirmation in order to investigate the potentials of anti-galectin-1 therapies.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-10"},"PeriodicalIF":3.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2025-05-16DOI: 10.1159/000545488
Miguel A Idoate, Mikel Ariz-Galilea, Ainhoa Urbiola-Casales, Miriam Alonso-García, Jesús Machuca-Aguado, Carlos Ortiz de Solórzano, Eloy Rivas-Infante, Rainiero Avila-Polo, Michele Biscuola
{"title":"Immune Scenario Identification Combining Multiplexed, Quantitative, and Advanced Imaging Analysis Could Be Relevant in Immunotherapy against Glioblastoma and Grade 4 Astrocytoma.","authors":"Miguel A Idoate, Mikel Ariz-Galilea, Ainhoa Urbiola-Casales, Miriam Alonso-García, Jesús Machuca-Aguado, Carlos Ortiz de Solórzano, Eloy Rivas-Infante, Rainiero Avila-Polo, Michele Biscuola","doi":"10.1159/000545488","DOIUrl":"10.1159/000545488","url":null,"abstract":"<p><strong>Introduction: </strong>In our research on understanding glioblastoma's resistance mechanisms to immunotherapy, we extensively investigated through an innovative technology that enables the simultaneous assessment of multiple biomarkers. With this approach, we aim to gain deeper insights into the interplay between immunosuppressive cells (ICs) and effector cells (ECs).</p><p><strong>Methods: </strong>One hundred twenty-six cases of glioblastoma were studied employing tissue microarrays stained with a panel of immune infiltrate validated via multiplex immunofluorescence and quantified by advanced image analysis. All cases were categorized according to an EC/IC ratio and their respective medians. Statistical correlations between cell populations and with survival were calculated.</p><p><strong>Results: </strong>M2 macrophages were the most abundant ICs, followed by a variable number of ECs and protumoral activated microglia, and a scant quantity of FoxP3 cells. EC showed a statistically significant direct positive correlation with ICs. The patients with tumors exhibiting an EC/IC ratio ≤0.063 displayed a significantly poorer outcome. Furthermore, in the context of incomplete surgical resection, significant differences were evident considering immune scenarios.</p><p><strong>Conclusions: </strong>By integrating multiplex technology with advanced imaging analysis, we successfully identified 4 distinct immune scenarios in glioblastoma. We observed a favorable immune scenario characterized by a relatively high EC/IC ratio, which is especially evident in the clinical setting of incomplete tumor resection. This promising immune scenario holds significant potential for selecting suitable candidates for immunotherapy in glioblastoma.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-20"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2025-01-01Epub Date: 2024-11-11DOI: 10.1159/000542465
Maria Frantzi, Ana C Morillo, Guillermo Lendinez, Ana Blanca, Daniel Lopez Ruiz, Jose Parada, Isabel Heidegger, Zoran Culig, Emmanouil Mavrogeorgis, Antonio Lopez Beltran, Marina Mora-Ortiz, Julia Carrasco-Valiente, Harald Mischak, Rafael A Medina, Pablo Campos Hernandez, Enrique Gómez Gómez
{"title":"Validation of a Urine-Based Proteomics Test to Predict Clinically Significant Prostate Cancer: Complementing mpMRI Pathway.","authors":"Maria Frantzi, Ana C Morillo, Guillermo Lendinez, Ana Blanca, Daniel Lopez Ruiz, Jose Parada, Isabel Heidegger, Zoran Culig, Emmanouil Mavrogeorgis, Antonio Lopez Beltran, Marina Mora-Ortiz, Julia Carrasco-Valiente, Harald Mischak, Rafael A Medina, Pablo Campos Hernandez, Enrique Gómez Gómez","doi":"10.1159/000542465","DOIUrl":"10.1159/000542465","url":null,"abstract":"<p><strong>Introduction: </strong>Prostate cancer (PCa) is the most frequently diagnosed cancer among men. A major clinical need is to accurately predict clinically significant PCa (csPCa). A proteomics-based 19-biomarker model (19-BM) was previously developed using capillary electrophoresis-mass spectrometry (CE-MS) and validated in close to 1,000 patients at risk for PCa. This study aimed to validate 19-BM in a multicenter prospective cohort of 101 biopsy-naive patients using current diagnostic pathways.</p><p><strong>Methods: </strong>Urine samples from 101 patients with suspicious of PCa were analyzed using CE-MS. All patients underwent multiparametric or magnetic resonance imaging (mpMRI) using a 3-T system. The 19-BM score was estimated using support vector machine-based software (MosaCluster v1.7.0), employing the previously published cut-off criterion of -0.07. Diagnostic nomograms were investigated along with mpMRI.</p><p><strong>Results: </strong>Independent validation of 19-BM yielded a sensitivity of 77% and a specificity of 85% (AUC:0.81). This performance surpassed those of prostate-specific antigen (PSA; AUC:0.56) and PSA density (AUC:0.69). For PI-RADS≤ 3 patients, 19-BM showed a sensitivity of 86% and a specificity of 88%. Integrating 19-BM with mpMRI resulted in significantly better accuracy (AUC:0.90) compared to individual investigations alone (AUC19BM = 0.81; p = 0.004 and AUCmpMRI: 0.79; p = 0.001). Examining the decision curve analysis, 19-BM with mpMRI surpassed other approaches for the prevailing risk interval from a 30% cut-off.</p><p><strong>Conclusions: </strong>19-BM exhibited favorable reproducibility for the prediction of csPCa. In patients with PI-RADS ≤3, 19-BM correctly classified 88% of the patients with insignificant PCa at the cost of 1 missed csPCa patient. Utilizing the 19-BM test could prove valuable in complementing mpMRI and reducing the need for unnecessary biopsies.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"99-108"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2025-01-01Epub Date: 2024-12-10DOI: 10.1159/000543006
Eri Tanaka, Naoko Taniura, Ken-Ichi Mukaisho, Yusuke Kageyama, Mai Noujima, Hirohito Ishigaki, Takahisa Nakayama, Ryoji Kushima
{"title":"Metabolic Analysis of Three-Dimensional Cultured Gastrointestinal Cancer Cells Suggests that <sc>l</sc>-Arginine Inhibits Tumor Growth by Affecting the Urea Cycle.","authors":"Eri Tanaka, Naoko Taniura, Ken-Ichi Mukaisho, Yusuke Kageyama, Mai Noujima, Hirohito Ishigaki, Takahisa Nakayama, Ryoji Kushima","doi":"10.1159/000543006","DOIUrl":"10.1159/000543006","url":null,"abstract":"<p><strong>Introduction: </strong>There is evidence for the anticancer effects of <sc>l</sc>-arginine (arginine); however, the direct effects on cancer cells and mechanism of action are unclear.</p><p><strong>Methods: </strong>Various upper gastrointestinal cancer cells (OE19, OE33, MKN1, MKN45, MKN74, and AGS) were divided into arginine-treated and -untreated groups and cultured using two-dimensional and three-dimensional culture systems. Proliferation was evaluated using the MTT assay to identify arginine-sensitive (OE33) and arginine-insensitive (OE19) strains. Furthermore, the effects of arginine were evaluated using a mitochondrial stress test, cell cycle assay, comprehensive metabolic analysis, and tracer study using (13C6) <sc>l</sc>-arginine.</p><p><strong>Results: </strong>In OE33 (but not in OE19), the maximal respiratory capacity of mitochondria was lower in the treated group than in the control group. In OE33, S phase cells (determined using BrdU) were significantly reduced. In a comprehensive metabolic analysis of OE33, citrulline/ornithine levels were significantly lower in arginine-treated than in untreated cells. Using OE33, carbamoyl aspartic acid (CAA) levels were significantly lower in arginine-treated than in untreated cells. A tracer study suggested that arginine promotes the urea cycle.</p><p><strong>Conclusion: </strong>Arginine affected urea cycle metabolism, thereby decreasing CAA, which is required for pyrimidine nucleotide synthesis. These findings provide insight into the mechanism underlying the anticancer effects of arginine.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"133-149"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2025-01-01Epub Date: 2025-03-13DOI: 10.1159/000545229
Fatma Al Hinai, Ruqaiya Al Shamsi, Samya Al Husaini, Afrah Al Rashdi, Mohammad Arafa
{"title":"The Role of Cytokeratin 7 and Cytokeratin 19 Immunohistochemistry in the Evaluation of Human Papillomavirus-Induced Cervical Squamous Precursor Epithelial Lesions.","authors":"Fatma Al Hinai, Ruqaiya Al Shamsi, Samya Al Husaini, Afrah Al Rashdi, Mohammad Arafa","doi":"10.1159/000545229","DOIUrl":"10.1159/000545229","url":null,"abstract":"<p><strong>Introduction: </strong>Cervical cancer is the fourth common cancer in women worldwide. In most cases, the disease is induced by persistent high-risk human papillomavirus (HPV) infection. This study aimed to assess the role of cytokeratin 7 (CK7) and cytokeratin 19 (CK19) in HPV-induced cervical epithelial lesions using tissue microarray (TMA).</p><p><strong>Methods: </strong>A retrospective cohort study included females with cervical low-grade intraepithelial lesion (LSIL), high-grade intraepithelial lesion (HSIL), and squamous cell carcinoma (SCC). TMA was constructed using specimens of 270 cases and 233 control tissues. CK7 and CK19 immunohistochemistry was scored as negative or positive. Follow-up information was gathered.</p><p><strong>Results: </strong>CK7 was negative in about 85% of LSILs and positive in 55% of HSILs (p < 0.001). CK19 showed positivity in about 50% of LSILs and 77% of the HSILs (p < 0.001). For cases with available follow-up data, about 69% of CK7-positive LSILs progressed to higher grade lesions and 64% of CK7-positive HSILs showed progression to higher grades (CIN2 to CIN3) or to SCC. Regarding CK19, nearly 66% positive LSILs progressed to HSIL whereas, 62% of positive HSILs showed progression. LSILs with positivity for both markers progressed to HSIL in 70% of cases.</p><p><strong>Conclusion: </strong>CK7 and CK19 positivity are significantly associated with higher grade HPV-induced cervical lesions. Lesions with combined CK7 and CK19 positivity have a higher risk of progression to higher grade lesions.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"216-223"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2025-01-01Epub Date: 2024-10-09DOI: 10.1159/000541664
Leyla Arslan Bozdag, Sibel Elif Gultekin
{"title":"Human Papilloma Virus-Related Oral Mucosal Lesions in Turkey: A Retrospective Cohort Study.","authors":"Leyla Arslan Bozdag, Sibel Elif Gultekin","doi":"10.1159/000541664","DOIUrl":"10.1159/000541664","url":null,"abstract":"<p><strong>Introduction: </strong>The human papillomavirus (HPV) is the etiological agent of a variety of oral mucosal benign and pre/malignant lesions, which demonstrate a wide range of prevalence according to geographic regions.</p><p><strong>Material and methods: </strong>This study specifically examined the typing of HPV-associated oral mucosal lesions in Turkish patients. The DNA from FFPE blocks of 228 lesions was utilized for this purpose. A total of 87 oral mucosal lesions were classified as benign, 68 as premalignant, and 73 as malignant. DNA from these lesions was amplified using polymerase chain reaction, and genotypes were identified using restriction fragment length polymorphisms (RFLP).</p><p><strong>Results: </strong>HPV-DNA was identified in 17 out of 228 patients, indicating a prevalence incidence of 7.4%. In benign oral lesions, the prevalence of HPV-DNA was 9.2% (8/87 cases), whereas in premalignant, oral epithelial dysplasia, and oral squamous cell carcinoma lesions, it was 6.9% (9/141 cases). A significant statistical difference was found between patients who tested positive for HPV and those who tested negative in terms of the location of the lesion and the age of the patients (p = 0.0097, p = 0.02, respectively).</p><p><strong>Conclusions: </strong>This study underscores the considerable prevalence of HPV infection in oral mucosal lesions among individuals in Central Anatolia, Turkey.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"90-98"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2025-01-01Epub Date: 2024-08-27DOI: 10.1159/000540790
Ayat G Lashen, Michael S Toss, Catrin S Rutland, Andrew R Green, Nigel P Mongan, Emad Rakha
{"title":"Prognostic and Clinical Significance of the Proliferation Marker MCM7 in Breast Cancer.","authors":"Ayat G Lashen, Michael S Toss, Catrin S Rutland, Andrew R Green, Nigel P Mongan, Emad Rakha","doi":"10.1159/000540790","DOIUrl":"10.1159/000540790","url":null,"abstract":"<p><strong>Introduction: </strong>Minichromosome maintenance complex component 7 (MCM7) plays an essential role in proliferation and DNA replication of cancer cells. However, the expression and prognostic significance of MCM7 in breast cancer (BC) remain to be defined. In this study, we aimed to evaluate the role of MCM7 in BC.</p><p><strong>Methods: </strong>We conducted immunohistochemistry staining of MCM7 in 1,156 operable early-stage BC samples and assessed MCM7 at the transcriptomic levels using publicly available cohorts (n = 13,430). MCM7 expression was evaluated and correlated with clinicopathological parameters including Ki67 labelling index and patient outcome.</p><p><strong>Results: </strong>At the transcriptomic level, there was a significant association between high MCM7 mRNA levels and shorter patient survival in the whole cohort and in luminal BC class but not in the basal-like molecular subtype. High MCM7 protein expression was detected in 43% of patients and was significantly associated with parameters characteristic of aggressive tumour behaviour. MCM7 was independently associated with shorter survival, particularly in oestrogen receptor-positive (luminal) BC. MCM7 stratified luminal tumours with aggressive clinicopathological features into distinct prognostic groups. In endocrine therapy-treated BC patients, high MCM7 was associated with poor outcome, but such association disappeared with administration of adjuvant chemotherapy. Patients with high expression of Ki67 and MCM7 showed worst survival, while patients with double low expression BC showed the best outcome compared with single expression groups.</p><p><strong>Conclusion: </strong>The current findings indicate that MCM7 expression has a prognostic value in BC and can be used to identify luminal BC patients who can benefit from adjuvant chemotherapy.</p><p><strong>Introduction: </strong>Minichromosome maintenance complex component 7 (MCM7) plays an essential role in proliferation and DNA replication of cancer cells. However, the expression and prognostic significance of MCM7 in breast cancer (BC) remain to be defined. In this study, we aimed to evaluate the role of MCM7 in BC.</p><p><strong>Methods: </strong>We conducted immunohistochemistry staining of MCM7 in 1,156 operable early-stage BC samples and assessed MCM7 at the transcriptomic levels using publicly available cohorts (n = 13,430). MCM7 expression was evaluated and correlated with clinicopathological parameters including Ki67 labelling index and patient outcome.</p><p><strong>Results: </strong>At the transcriptomic level, there was a significant association between high MCM7 mRNA levels and shorter patient survival in the whole cohort and in luminal BC class but not in the basal-like molecular subtype. High MCM7 protein expression was detected in 43% of patients and was significantly associated with parameters characteristic of aggressive tumour behaviour. MCM7 was independently associated with shorter survival","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"18-27"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2025-01-01Epub Date: 2024-09-06DOI: 10.1159/000541299
Miseon Lee, Ahwon Lee, Byung-Ock Choi, Woo-Chan Park, Jieun Lee, Jun Kang
{"title":"p16 Immunohistochemical Patterns in Triple-Negative Breast Cancer: Clinical and Genomic Similarities of the p16 Diffuse Pattern to pRB Deficiency.","authors":"Miseon Lee, Ahwon Lee, Byung-Ock Choi, Woo-Chan Park, Jieun Lee, Jun Kang","doi":"10.1159/000541299","DOIUrl":"10.1159/000541299","url":null,"abstract":"<p><strong>Introduction: </strong>Triple-negative breast cancer (TNBC) is associated with alterations in the retinoblastoma pathway. As a consequence of retinoblastoma protein (pRB) loss, compensatory upregulation of p16 occurs due to the loss of phosphorylated pRB-mediated negative feedback on p16 expression. The aim of this study is to investigate the clinicopathological and genomic characteristics associated with the diffuse pattern of p16 immunohistochemistry (IHC) in TNBC.</p><p><strong>Methods: </strong>The study analyzed surgically resected TNBC for whole-exome sequencing in 113 cases and for cDNA microarray in 144 cases. The p16 IHC results were classified into two patterns: diffuse and negative/mosaic.</p><p><strong>Results: </strong>In the entire cohort (n = 257), the diffuse pattern of p16 IHC was observed in 123 (47.9%) patients and the negative/mosaic pattern in 134 (52.1%). Biallelic RB1 inactivation was observed in 14.3% of patients with the diffuse pattern. The diffuse pattern of p16 IHC showed more frequent RB1 alterations and cell cycle progression signatures, a higher Ki-67 labeling index, more frequent chromosome segment copy number changes, a higher frequency of homologous recombination deficiency high, and immune-related signatures. PIK3CA mutations were more frequent in the negative/mosaic pattern. CCND1 amplification was identified in 5 cases, all with the negative/mosaic pattern.</p><p><strong>Conclusion: </strong>In TNBC, the diffuse p16 pattern shows clinical and genomic similarities to pRB-deficient tumors, suggesting shared characteristics. This suggests that p16 IHC testing may provide new therapeutic approaches, underscoring its potential clinical importance.</p><p><strong>Introduction: </strong>Triple-negative breast cancer (TNBC) is associated with alterations in the retinoblastoma pathway. As a consequence of retinoblastoma protein (pRB) loss, compensatory upregulation of p16 occurs due to the loss of phosphorylated pRB-mediated negative feedback on p16 expression. The aim of this study is to investigate the clinicopathological and genomic characteristics associated with the diffuse pattern of p16 immunohistochemistry (IHC) in TNBC.</p><p><strong>Methods: </strong>The study analyzed surgically resected TNBC for whole-exome sequencing in 113 cases and for cDNA microarray in 144 cases. The p16 IHC results were classified into two patterns: diffuse and negative/mosaic.</p><p><strong>Results: </strong>In the entire cohort (n = 257), the diffuse pattern of p16 IHC was observed in 123 (47.9%) patients and the negative/mosaic pattern in 134 (52.1%). Biallelic RB1 inactivation was observed in 14.3% of patients with the diffuse pattern. The diffuse pattern of p16 IHC showed more frequent RB1 alterations and cell cycle progression signatures, a higher Ki-67 labeling index, more frequent chromosome segment copy number changes, a higher frequency of homologous recombination deficiency high, and immune-related signatures. PIK","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"63-76"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2025-01-01Epub Date: 2025-04-18DOI: 10.1159/000545971
Levente Kuthi, Levente Kuthi, Márton Csaba Gráczia, Imola Adamik, Zsombor Melegh, Zsófia Küronya, Mahmut Akgul
{"title":"Metastatic Prostatic Adenocarcinoma to the Penis with Diffuse P16 Expression: Recognizing a Diagnostic Pitfall.","authors":"Levente Kuthi, Levente Kuthi, Márton Csaba Gráczia, Imola Adamik, Zsombor Melegh, Zsófia Küronya, Mahmut Akgul","doi":"10.1159/000545971","DOIUrl":"10.1159/000545971","url":null,"abstract":"<p><strong>Introduction: </strong>Prostate cancer (PCa) is the most common malignant tumor in men, with acinar adenocarcinoma as the predominant subtype. While PCa metastases typically affect bones, penile metastases are exceedingly rare. Penile tumors are generally squamous cell carcinoma (SCC), with p16 overexpression often used as a surrogate marker for oncogenic human papillomavirus (HPV) infection.</p><p><strong>Case presentation: </strong>We report the case of an 85-year-old male with a history of PCa (grade group 5) treated with irradiation and hormonal therapy, who presented with a progressive penile lesion initially misdiagnosed as HPV-associated SCC. Immunohistochemistry revealed diffuse panCK, p16, NKX3.1, androgen receptor, and ERG positivity, with Rb1 protein loss confirming metastatic PCa. Prostate-specific antigen levels remained within the normal range, complicating the diagnosis.</p><p><strong>Conclusion: </strong>This case emphasizes the importance of thorough clinicopathological correlation in unusual metastatic presentations and highlights that p16 overexpression, even in penile tumors, may indicate Rb1 inactivation rather than HPV-related SCC.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"294-299"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}