Journal of Pathology Clinical Research最新文献

{"title":"Alcian blue-positive stromal phenotype in basal cell carcinoma is associated with progression on first-line hedgehog inhibitors","authors":"Viola K DeTemple,&nbsp;Rudolf Stadler,&nbsp;Sabine Bredemeier,&nbsp;Sungyoung Chung,&nbsp;Katrin Schaper-Gerhardt,&nbsp;Mareike Alter,&nbsp;Yenny Angela,&nbsp;Henner Stege,&nbsp;Ulrike Leiter,&nbsp;Jan Ohletz,&nbsp;Elisabeth Livingstone,&nbsp;Imke von Wasielewski,&nbsp;Jessica C Hassel,&nbsp;Julia Huynh,&nbsp;Christoffer Gebhardt,&nbsp;Claudia Pföhler,&nbsp;Ralf Gutzmer,&nbsp;Christina H Scheel","doi":"10.1002/2056-4538.70074","DOIUrl":"10.1002/2056-4538.70074","url":null,"abstract":"<p>Basal cell carcinoma (BCC) is the most frequent malignancy in fair-skinned populations. Although curable in most cases, approximately 4% of patients develop locally advanced or metastatic disease (advBCC) requiring systemic therapy. Hedgehog pathway inhibitors (HHIs; vismodegib/sonidegib) constitute standard first-line treatment, yet individual responses vary and no histopathological biomarker predicting therapeutic outcome exists. We conducted a retrospective, multicenter analysis of 70 BCCs encompassing clinically common and advanced stages. Routine hematoxylin and eosin and Alcian blue (AB; pH 2.5) staining was evaluated using a 17-parameter, numerically encoded histopathology matrix spanning tumor morphology, stromal composition, and immune contexture. Data were mapped by unsupervised hierarchical clustering. Distinct AB staining patterns were observed: superficial and nodular BCCs typically exhibited an AB-positive peritumoral border, whereas infiltrative and sclerosing subtypes displayed a diffuse AB-positive desmoplastic stroma. The latter also correlated with advanced EADO clinical stages (correlation coefficients 0.46–0.48; <i>p</i> &lt; 0.001). In a subset of 30 advBCCs obtained before or during HHI therapy, AB-positive stroma was the only parameter independently associated with shorter progression-free survival (multivariable hazard ratio = 23.8; 95% CI 4.02–141.3; <i>p</i> &lt; 0.001). Established clinical or histological features failed to associate with outcome. Our findings identify diffuse AB-positive stroma as a readily detectable feature of histologically aggressive BCC and as a candidate biomarker associated with progression under HHI treatment. Because AB staining is routine, inexpensive, and easily standardized, this phenotype represents an immediately implementable readout for prospective validation and a potential link between extracellular-matrix remodeling and therapy resistance in BCC.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12810521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145991384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the association between homologous recombination deficiency scores and treatment response in localized and metastatic prostate cancer","authors":"Qiyu Zhu,&nbsp;Yifu Shi,&nbsp;Ting Wang,&nbsp;Qian Zheng,&nbsp;Xiuya Zhou,&nbsp;Zehua Tan,&nbsp;Junru Chen,&nbsp;Jingjing Guo,&nbsp;Haoyang Liu,&nbsp;Pengfei Shen,&nbsp;Hao Zeng,&nbsp;Jinge Zhao","doi":"10.1002/2056-4538.70069","DOIUrl":"10.1002/2056-4538.70069","url":null,"abstract":"<p>The aim of this study was to evaluate the predictive value of homologous recombination deficiency scores for therapeutic efficacy in prostate cancer across various disease stages under different regimens. We collected tissue samples from 167 prostate cancer patients and performed genomic sequencing to assess homologous recombination deficiency scores. Among them, 67 patients with localized disease received radical prostatectomy, and 100 patients with metastatic disease received androgen receptor target inhibitor treatment. We examined the predictive value of homologous recombination deficiency scores in forecasting the therapeutic efficacy of standard-of-care treatment of prostate cancer under different disease stages. Among patients who underwent radical prostatectomy, those with higher homologous recombination deficiency scores experienced notably shorter biochemical progression-free survival and overall survival than those with lower scores (median biochemical progression-free survival: 50.6 versus 148.4 months, <i>p</i> = 0.037; median overall survival: 149.0 months versus not reached, <i>p</i> = 0.0018). In patients receiving androgen receptor pathway inhibitor treatment, men with higher homologous recombination deficiency scores exhibited reduced prostate-specific antigen progression-free survival, radiographic progression-free survival, and overall survival compared to the lower score group at the metastatic castration-resistant stage (median prostate-specific antigen progression-free survival: 8.17 versus 24.17 months, <i>p</i> = 0.032; median radiographic progression-free survival: 11.8 versus 24.8 months, <i>p</i> = 0.015; median overall survival: 36.5 months versus not reached, <i>p</i> = 0.056) and a deteriorating trend in the metastatic hormone-sensitive stage. Molecular characterization showed that higher homologous recombination deficiency scores were associated with higher alteration rates in genes such as <i>BRCA2</i>, <i>CDK12</i>, <i>MYC</i>, and <i>PTEN</i>. This study reveals that higher homologous recombination deficiency scores are associated with unfavorable treatment efficacy of radical prostatectomy in localized prostate cancer and of androgen receptor target inhibitor treatment in metastatic prostate cancer.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12802083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148078749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of beta-adrenergic receptor expression in oesophageal adenocarcinoma","authors":"Talita Oliveira,&nbsp;Swathi Sasi,&nbsp;James Trainor,&nbsp;Damian T McManus,&nbsp;Stephen McQuaid,&nbsp;Claire Lewis,&nbsp;Jacqueline A James,&nbsp;Helen G Coleman,&nbsp;Úna C McMenamin,&nbsp;Richard C Turkington","doi":"10.1002/2056-4538.70070","DOIUrl":"10.1002/2056-4538.70070","url":null,"abstract":"<p>Expression of the β-adrenergic receptors' family has been associated with survival outcomes in multiple different cancer types, showing their potential to act as prognostic factors. No previous work has evaluated these receptors in relation to survival in oesophageal adenocarcinoma. We sought to analyse the expression of β₁ and β₂ adrenergic receptors in oesophageal adenocarcinoma and their association with survival outcomes. The expression of β₁ and β₂ adrenergic receptors was evaluated in a cohort of oesophageal adenocarcinoma patients treated with neo-adjuvant chemotherapy prior to surgical resection at the Northern Ireland Cancer Centre between 2004 and 2012. Immunohistochemical staining for was assessed using a Tissue Microarray with triplicate tumour cores. Cox proportional hazards regression was used to investigate the association of β₁ and β₂ adrenergic receptor expression with survival outcomes, including adjustment for clinical factors. In total, 115 and 122 patients were assessed for β₁ and β₂ adrenergic receptor expression, respectively. In adjusted analysis, high β₂ adrenergic receptor expression was associated with improved recurrence-free [hazard ratio [HR] 0.57, 95% CI 0.33–0.97] and overall survival (HR 0.53, 95% CI 0.30–0.94) with restriction to gastro-oesophageal junction tumours showing a stronger association with improved overall survival (HR 0.27, 95% CI 0.13–0.59). No significant association was observed for β₁ adrenergic receptor expression and any survival outcome. In summary, we found that higher expression of the β₂ adrenergic receptor was associated with a significant improvement in survival in oesophageal adenocarcinoma patients, and gastro-oesophageal junction tumours in particular, treated with neoadjuvant chemotherapy followed by surgical resection.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12765628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148065277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148099421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementing Immunoscore in colorectal cancer: lessons from cohort studies, limitations and barriers to adoption","authors":"Matthew SS Hsu,&nbsp;Suet Yi Leung","doi":"10.1002/2056-4538.70071","DOIUrl":"10.1002/2056-4538.70071","url":null,"abstract":"<p>The Immunoscore (IS) quantifies the immune contexture of colorectal cancer (CRC) by measuring CD3⁺ and CD8⁺ T-cell densities in the tumour centre and invasive margin, providing superior prognostic performance compared with TNM staging and mismatch-repair (MMR) status alone. Large international cohort studies have validated its ability to predict benefit from adjuvant chemotherapy in stage III colon cancer. More recently, Immunoscore-IC – a refined version that incorporates PD-L1⁺ cell density and spatial interactions – has emerged as the first biomarker capable of identifying the subset of patients with proficient-MMR (pMMR/MSS) metastatic CRC who derive significant benefit from immune checkpoint inhibitors. Despite these advances, technical requirements, biological limitations, and reliance on retrospective data continue to hinder widespread clinical adoption. Addressing some of these challenges could enhance its utility and facilitate broader integration into routine pathology practice. In this commentary, we place landmark IS publications within the evolving research landscape, including papers published in <i>The Journal of Pathology Clinical Research</i>; integrate findings from recent international validation cohorts and adjuvant trials; and highlight the growing evidence supporting IS as a robust prognostic tool with clear predictive implications for both chemotherapy and immunotherapy in CRC.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12746701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145851132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148099422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic utility and pitfalls of human T-lymphotropic virus serology in adult T-cell leukemia/lymphoma: evidence from a 25-year pathology-based nonendemic cohort","authors":"Chang-Tsu Yuan,&nbsp;Li-Yu Sun,&nbsp;Shih-Sung Chuang,&nbsp;Kennosuke Karube,&nbsp;Hsiao-Bai Yang,&nbsp;Sze-Hwei Lee,&nbsp;Ren-Ching Wang,&nbsp;Kung-Chao Chang,&nbsp;Chein-Jun Kao,&nbsp;Huai-Hsuan Huang,&nbsp;Wen-Chien Chou","doi":"10.1002/2056-4538.70072","DOIUrl":"10.1002/2056-4538.70072","url":null,"abstract":"<p>Adult T-cell leukemia/lymphoma (ATLL) is a distinct type of peripheral T-cell lymphoma (PTCL) driven by human T-lymphotropic virus type I (HTLV-1)–infected T cells, but diagnosis can be confounded by histological overlap with non-ATLL PTCL. While molecular testing is the diagnostic gold standard in endemic areas, HTLV-1/2 serology is often used as a surrogate in nonendemic settings, yet its accuracy and limitations remain unclear. We retrospectively analyzed 881 PTCL cases over 25 years at two tertiary referral hospitals in Taiwan, where HTLV-1 is nonendemic. Serology was available in 48.2% of cases. Molecular confirmation was performed using <i>HBZ in situ</i> hybridization and <i>tax</i> quantitative polymerase chain reaction. Among the 44 seropositive PTCL patients with tissue available, 37 were diagnosed and molecularly confirmed as ATLL. Of the seven initially diagnosed as non-ATLL PTCL, three were reclassified as ATLL, while four showed no molecular evidence, including three likely false seropositives with borderline signal-to-cutoff (S/CO) values in serology assay and T follicular helper cell phenotype. In seropositive PTCL, clinicopathologic interpretation without molecular testing yielded 100% positive predictive value, 93% sensitivity, and 93% accuracy, compared with 91% positive predictive value by serology alone. In addition, retrospective molecular screening in 59 PTCL without prior serologic data revealed one case of ATLL that had initially been overlooked. In conclusion, our findings support routine HTLV-1/2 serologic testing in all newly diagnosed PTCLs. However, interpretation should be guided by clinicopathological correlation and serology index values. Borderline index results warrant molecular confirmation.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12748522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145858390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"12 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148081539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}