Asmaa H Mohamed, Aziza E Abdelrahman, Moamna M Fahmy, Ahmad B Waley, Mohamed Saleh, Abdelfatah H Abdelwanis, Ahmed I Khalil, Enas M Fouad
{"title":"Prognostic Interplay of Caveolin1 and FOXC1 in Early Nonmetastatic Triple Negative Breast Cancer Undergoing Neoadjuvant Chemotherapy.","authors":"Asmaa H Mohamed, Aziza E Abdelrahman, Moamna M Fahmy, Ahmad B Waley, Mohamed Saleh, Abdelfatah H Abdelwanis, Ahmed I Khalil, Enas M Fouad","doi":"10.1097/PAI.0000000000001282","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001282","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) lacks specific molecular targets. This highlights an obvious need to identify specific prognostic biomarkers to stratify patients and guide treatment decisions. We designed this study to evaluate CAV1 and FOXC1 immunohistochemical expression and their correlation to survival outcomes and response to neoadjuvant chemotherapy (NAC). CAV1 and FOXC1 expressions were analyzed in 50 cases of TNBC. Clinical data on overall survival (OS), progression-free survival (PFS), and NAC response were collected and statistically evaluated. The predominant histologic subtype was invasive carcinoma of no special type (78%), with most cases being grade II (56%). CAV1 positivity was observed in 24% of cases, while FOXC1 was expressed in 74%. FOXC1 was significantly associated with higher tumor grade (P=0.02), advanced stage (P<0.001), and nodal involvement (P=0.002). It also correlated with poor NAC response and worse OS and PFS (P=0.001 and 0.01, respectively). There was a significant association of CAV1 with grade (P=0.002), lymph node involvement (P=0.003), stage (P=0.01), unfavorable clinical and pathologic response to NAC (P<0.001, P=0.01), and poor OS and PFS (P<0.001 for each). Conclusions: Both CAV1 and FOXC1 may serve as adverse prognostic indicators in TNBC. Their overexpression suggests a potential lack of benefit from NAC, indicating that targeted therapies against these markers might be more effective.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Extranodal Histiocytic Sarcoma: A Clinicopathologic Study of Two Cases and Literature Review.","authors":"Jiayu Li, Qiong Liao","doi":"10.1097/PAI.0000000000001287","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001287","url":null,"abstract":"<p><p>Histiocytic sarcoma (HS) is an extremely rare hematopoietic neoplasm derived from the monocytic/histiocytic/dendritic cell lineage. While sporadic cases of primary soft-tissue HS have been reported, its clinicopathological and molecular features remain incompletely characterized. This study investigates the clinicopathological features of two cases of soft-tissue HS and reviews the relevant literature. Microscopically, the tumor cells exhibited a diffuse growth pattern, with morphologic features varying from spindle-shaped sarcomatoid to epithelioid subtypes. Occasional bizarre cells were observed. Immunohistochemically, the tumor cells were positive for CD68, Lysozyme, S100, CD4, and CD163, but negative for a comprehensive panel of markers, including those for myeloid, Langerhans, follicular dendritic, lymphoid (T, B, NK), epithelial, vascular endothelial, and melanocytic lineages. Next-generation sequencing (NGS) revealed distinct mutational profiles: Case 1 harbored mutations in BRAF V600E, BRAF V600E, CDKN2A, and CIITA, while Case 2 exhibited mutations in CREBBP, INPP4B, RB1, PTEN, KMT2D, MSH2, and TP53, which may contribute to tumorigenesis and progression. Despite therapeutic efforts, both patients died within 6 and 9 months of follow-up, respectively. In conclusion, HS is a diagnostically challenging malignancy due to its rarity and morphological overlap with other soft tissue tumors. Immunohistochemical markers (CD68, Lysozyme, S100, CD4, CD163) are essential for diagnosis. Currently, no standard treatment exists. This study characterizes the molecular profiles of two extranodal HS cases, contributing to the understanding of their clinicopathological and genetic features.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"E2F7/Beclin-1 Pathway: Influencing Autophagy and EMT in ccRCC.","authors":"Junlin Zhao, Xinyi Yan, Dongmei Zhang, Xiuming Li, Xiao Wang, Yali Zhang","doi":"10.1097/PAI.0000000000001288","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001288","url":null,"abstract":"<p><strong>Purpose: </strong>The deficiency of the current study of ccRCC lies in the incomplete understanding of the interaction between the E2F7/Beclin-1 pathway, autophagy, and EMT. This study aims to investigate the influence of the E2F7/Beclin-1 pathway on autophagy and EMT in human ccRCC.</p><p><strong>Methods: </strong>An entire collection of 24 samples, including ccRCC tissues and their corresponding adjacent tissues, were selected for this study. Immunohistochemistry was implemented to analyze the expression and distribution of E2F7 in ccRCC tissues and adjacent tissues. Western blot techniques and RT-qPCR were used to measure the amounts of E2F7 protein and mRNA expression in ccRCC alongside adjacent tissues, as well as autophagy-related molecule Beclin-1, LC3, and EMT-related molecule E-cadherin. Analysis was done on the relationship between clinical pathologic characteristics and E2F7 expression. In vitro mechanistic validation was conducted using the ccRCC cell line (786-0 cells) transfected with E2F7 overexpression plasmid and E2F7-specific inhibitor si-E2F7.</p><p><strong>Results: </strong>Comparing ccRCC tissues to surrounding tissues, Beclin-1, LC3, and E-cadherin expression levels decreased considerably. Conversely, ccRCC tissues exhibited considerably higher expression levels of E2F7. Silencing E2F7 increased protein and mRNA expression levels of Beclin-1, LC3, and E-cadherin.</p><p><strong>Conclusion: </strong>In renal cancer tissues, a robust inverse correlation was detected between the expression of E2F7 and that of Beclin-1, LC3, and E-cadherin. E2F7 expression showed a substantial beneficial association. Notably, elevated E2F7 expression was associated with advanced clinical and pathologic stages of the tumor. A dual-luciferase assay confirmed the interaction between E2F7 and Beclin-1.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anne-Laure Désage, Simon Pointel, Eric Ezingeard, Sophie Bayle-Bleuez, Daniel Pissaloux, Fabien Forest
{"title":"SMARCA4-deficient Non-small Cell Lung Carcinoma Harboring ALK Fusion: A Case Report.","authors":"Anne-Laure Désage, Simon Pointel, Eric Ezingeard, Sophie Bayle-Bleuez, Daniel Pissaloux, Fabien Forest","doi":"10.1097/PAI.0000000000001289","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001289","url":null,"abstract":"<p><p>SMARCA4-deficient non-small cell lung cancers are usually of poor prognosis and associated with smoking-related mutations. Here, we report the case of a SMARCA4-deficient non-small cell lung cancer (NSCLC) occurring in a non-smoker female and harboring ALK fusion. Our case highlights for physicians to be especially cautious with molecular biological results in case of SMARCA4-deficient non-small cell lung cancer occurring in nonsmokers.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kala Gnanasekaran Kiruthiga, Sheren Younes, Brindhavan N Jaeger, Shuchun Zhao, Yasodha Natkunam
{"title":"Immune Checkpoint Molecule Indoleamine 2,3-Dioxygenase 1 (IDO1) Is Expressed in Lymphoma Subtypes With and Without Epstein-Barr Virus.","authors":"Kala Gnanasekaran Kiruthiga, Sheren Younes, Brindhavan N Jaeger, Shuchun Zhao, Yasodha Natkunam","doi":"10.1097/PAI.0000000000001286","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001286","url":null,"abstract":"<p><p>Indoleamine 2,3-dioxygenase 1 (IDO1) is an immune regulator involved in innate and acquired immunity and immune escape of tumors. Its expression in the tumor microenvironment of several solid tumors and lymphomas associated with Epstein-Barr virus (EBV), together with the promising results from clinical trials of IDO1 inhibitors, prompted us to evaluate IDO1 expression in a large cohort of 455 lymphomas including 154 cases associated with EBV. We optimized an immunohistochemical assay to evaluate IDO1 staining and show that IDO1 expression in seen in several lymphoma subtypes including classic Hodgkin lymphoma (CHL, 40%), diffuse large B-cell lymphoma (DLBCL, 23.5%), lymphoproliferative disorders in post-transplant settings (LPD-PT, 71.4%), extranodal NK/T-cell lymphoma (ENKTL, 92%), and ALK-negative anaplastic large cell lymphoma (ALCL, 39%), among others. Multiplex immunofluorescence further aided in refining the localization of IDO1 protein expression particularly within the tumor microenvironment. There was a significant correlation between IDO1 expression and EBV positivity in CHL (83.8%), LPD-PT (86.2%), and ENKTL (91.5%), with statistically significant difference in the mean IDO1 H-scores between EBV-positive and EBV-negative cases. IDO1 expression in ALCL was confined to ALK-negative cases with a significant correlation between IDO1 expression and ALK status. Our findings show that IDO1 expression is not only highly correlated with lymphomas associated with EBV, but also found in lymphomas unassociated with EBV, including aggressive and refractory subtypes of lymphomas for which immune checkpoint inhibition through IDO1 could be exploited for therapeutic purposes.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chuqiang Huang, Lili Tao, Xiaochen Ma, Zhihua Zhang, Min Su
{"title":"CD71 in Tandem With Ki-67 and p53: Unraveling Their Prognostic and Diagnostic Significance in Esophageal Squamous Cell Carcinoma and Precursor Lesions.","authors":"Chuqiang Huang, Lili Tao, Xiaochen Ma, Zhihua Zhang, Min Su","doi":"10.1097/PAI.0000000000001283","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001283","url":null,"abstract":"<p><strong>Background: </strong>Esophageal squamous cell carcinoma (ESCC), a commonly diagnosed cancer, poses challenges for early detection due to differentiation difficulties.</p><p><strong>Aims: </strong>To assess the diagnostic and prognostic value of CD71, Ki-67, and p53 in ESCC, intraepithelial neoplasia (IEN), and esophageal squamous simple hyperplasia (ESSH).</p><p><strong>Methods: </strong>We evaluated the diagnostic and prognostic performance of CD71, Ki-67, and p53 in 162 esophageal tissue samples (44 ESSH, 55 IEN, and 63 ESCC) using immunohistochemistry. Multivariate logistic regression model was used to train and validate, and ROC curve analysis was assessed diagnostic accuracy. Prognostic significance was evaluated using Kaplan-Meier survival analysis and Cox regression models.</p><p><strong>Results: </strong>Notably, CD71 positivity showed a stepwise increase across the progression of ESCC: 0% (0/44) in ESSH, 36.4% (20/55) in IEN, and 61.9% (39/63) in ESCC. The CD71-Ki-67-p53 panel demonstrated superior diagnostic precision (ESCC vs. ESSH: training AUC=0.996, test AUC=0.932) compared with Ki-67-p53 alone. In the context of esophageal cancer, low expression of CD71, Ki-67, or p53 was significantly associated with improved clinical outcomes (P<0.05). The CD71-Ki-67-p53 panel effectively stratified patients into high- and low-risk groups (P=0.004). Multivariate Cox regression confirmed the independent prognostic value of CD71-Ki-67-p53 panel (HR=0.064, P=0.013), after controlling for clinicopathological variables.</p><p><strong>Conclusion: </strong>The CD71-Ki-67-p53 immunohistochemical panel enhances diagnostic accuracy and prognostic stratification in esophageal lesions, offering a clinically valuable tool for early detection and personalized management. Further validation in larger cohorts is warranted to confirm its association with cancer progression and prognosis.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Monoamine Oxidase B Expression is a Prognostic Factor in Patients With Colorectal Cancer.","authors":"Jiyoon Jung, Jeong Won Kim, Joo Young Kim","doi":"10.1097/PAI.0000000000001285","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001285","url":null,"abstract":"<p><p>Monoamine oxidases (MAOs) produce hydrogen peroxide through an oxidative reaction and mediate the production of reactive oxygen species. MAO expression has been correlated with the prognosis in several tumor types. Accordingly, we aimed to evaluate MAOA and MAOB expression in patients with colorectal cancer (CRC) using immunohistochemistry as well as to assess their clinicopathologic behavior and prognostic significance. High MAOB expression (169 patients, 51.7%) was significantly associated with poor tumor differentiation, high pT classification, presence of lymphovascular invasion, lymph node metastasis, distant metastasis, and high MAOA expression. MAOA expression (245 patients, 74.9%) was not significantly correlated with any other clinicopathologic factors. Patients with high MAOB expression had significantly worse overall survival than those with low MAOB expression [hazard ratio (HR)=2.974; 95% CI: 1.855-4.767; P<0.001]. MAOA expression was not significantly correlated with overall survival in patients with CRC. Further, high MAOB expression (HR=1.680; 95% CI: 1.014-2.784; P=0.044) was an independent poor prognostic factor in patients with CRC. In conclusion, high MAOB expression is correlated with aggressive clinicopathologic behavior and may be a poor prognostic marker in patients with CRC.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinicopathological Features of Non-HPV-associated Common Differentiated Penile Squamous Cell Carcinoma: A Study of 55 Patients.","authors":"Yanan Zou, Li Zhang, Ping Yang, Guohua Yu, Di Sun","doi":"10.1097/PAI.0000000000001279","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001279","url":null,"abstract":"<p><p>To investigate the clinicopathological characteristics of non-HPV-related common differentiated penile squamous cell carcinoma, and to observe and analyze the changes of TP53 gene and the expression and significance of TP53, P16, programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR), androgen receptor (AR), human epidermal growth factor receptor-2 (HER2), and Ki67 proteins in tumor tissue. A total of 65 patients with penile squamous cell carcinoma diagnosed from May 2008 to May 2020 in Yantai Yuhuangding Hospital were retrospectively analyzed, and tumors were confirmed as non-HPV-associated common differentiated squamous cell carcinoma of the penis with negative HPV molecular tests in 55 patients. The relevant clinicopathological data of 55 patients were collected, and the TP53 gene mutation was detected by applying first-generation sequencing technology. And tumor tissue microarrays were prepared, and further immunohistochemical EnVision 2-step method was used to detect the expression levels of 7 of these proteins: TP53, P16, PD-L1, EGFR, AR, HER2, and Ki67. Pathologic grading non-HPV-associated common differentiated penile squamous cell carcinoma of 55 patients was G1 in 22 patients, G2 in 28 patients, and G3 in 5 patients. The tumor pathologic stage was pT1 in 22 patients, pT2 in 26 patients, pT3 in 6 patients, and pT4 in 1 case. Immunohistochemical markers showed positive expression of TP53 protein in about 84% (46/55 patients) and strong positive expression in about 20% of patients (11/55 patients), and the expression level of this protein was closely related to the pathologic grade and stage of the tumor. All patients showed negative expression of P16 protein. PD-L1 protein-positive expression patients accounted for about 35% (19/55 patients), among whom strong positive expression patients accounted for 20% (11/55 patients), and there was a correlation between PD-L1 protein expression level and the maximum tumor diameter. EGFR protein was positively expressed in 76% (42/55 patients) of patients and confirmed a significant correlation with the pathologic grade and stage of the tumor. The percentage of Ki67 protein-positive expression patients was 58% (32/55 patients) and significantly correlated with tumor pathology grade. In contrast, AR and HER2 proteins were negative in all 55 tumors. In 55 patients, except for 10 patients with failed DNA extraction, the mutation rate of TP53 gene in the remaining 45 patients was about 33% (15/45 patients), and the mutation sites were mainly concentrated in exon 5, followed by exon 8 and exon 5/8 combined mutation, and occasionally in exon 7/8 combined mutation. TP53 gene mutations were present in all positive TP53 protein expression intervals, and the highest rate of TP53 gene mutations was found in patients with ≥80% strong positive expression of TP53 protein, about 67% (6/9 patients). In addition, statistical analysis revealed a significant positive correlation between TP53 a","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ozgur Can Eren, Orhun Cig Taskin, Murat Oktay, Arzu Baygul, Fatma Aktepe, Nilgun Kapucuoglu
{"title":"Interobserver and Interassay Concordance in HER2 Immunohistochemistry: Implications on HER2-Low Breast Cancer.","authors":"Ozgur Can Eren, Orhun Cig Taskin, Murat Oktay, Arzu Baygul, Fatma Aktepe, Nilgun Kapucuoglu","doi":"10.1097/PAI.0000000000001281","DOIUrl":"https://doi.org/10.1097/PAI.0000000000001281","url":null,"abstract":"<p><p>Adopting a HER2-specific treatment approach for HER2-low breast cancer has been suggested after DESTINY-Breast04 (phase 3) trials. Hence, accurate pathologic evaluation gained higher importance, making interobserver agreement and interassay agreement questionable in this regard. To evaluate these, a cohort of 116 invasive breast cancer cases were stained with Dako A0485 and Ventana 4B5. Cases were evaluated by 5 observers independently and results were compared, together with in situ hybridization findings. Interobserver agreement (Kappa) for Ventana 4B5 and Dako A0485 were 0.62 and 0.63, respectively. Agreement was more prominent for IHC 3+ cases, followed by IHC 0 cases. Comparing the assays with one another, 74 cases had the same score in Ventana 4B5 and Dako A0485, while 37 and 5 cases had higher scores in Dako A0485 and Ventana 4B5, respectively. The results of the study demonstrate that pathologists are relatively unanimous on distinguishing 3+ cases (Kappa-0.76: Ventana/0.78: Dako), but have less consistency in 1+ or 2+ cases (Kappa-0.59: Ventana/0.60: Dako). It also illustrates that the case can obtain different HER2 IHC scores with different assays being used. Therefore, it is suggested for pathologists to recognize the pitfalls in HER2 IHC, be aware of the assay that is being used in their laboratory and hence evaluate the results in the accurate context.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144986088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Deciphering the Molecular Landscape of Urothelial Carcinoma: Immunohistochemistry-based Subtyping Using 4 Easily Available Antibodies for Cost-effective Stratification.","authors":"Shreeya Indulkar, B Vishal Rao, Debasmita Das, Mohan Krishna Pasam, Suseela Kodandapani, Rakesh Manilal Sharma, Subramanyeshwar Rao Thammineedi","doi":"10.1097/PAI.0000000000001272","DOIUrl":"10.1097/PAI.0000000000001272","url":null,"abstract":"<p><p>Molecular subtyping, though complex and typically reliant on costly and limited accessibility techniques, remains crucial for understanding the biology of urothelial carcinoma (UC). We sought a practical alternative by categorizing UCs into immunohistochemistry (IHC) subtypes using a panel of accessible antibodies. Examining 100 UCs from 2020 to 2021, encompassing both chemotherapy-naïve MIBC and NMIBC, acquired through transurethral resection or radical resection, we employed IHC with GATA3, KRT5, KRT14, and KRT20 markers on tissue microarrays. IHC luminal, IHC basal, IHC dual-positive, and IHC dual-negative subtypes were identified based on marker expressions. Positive staining criteria were established, considering >20% positive staining for specific markers. Results indicated a mean age of 64 years, with a 2.33:1 male-to-female ratio, and 60% NMIBC versus 40% MIBC. Subtypes identified were IHC luminal (55%), IHC basal (19%), IHC dual (22%), and IHC dual (4%). IHC luminal subtype demonstrated the highest overall survival rate (80%), followed by IHC dual (72.72%), IHC basal (63.15%), and IHC dual with the lowest survival (25%). KRT5-positive tumors exhibited a crude hazard ratio (HR) of 1.98 in univariate analysis, lacking statistical significance. Conversely, GATA3-positive tumors were significantly associated with lower risk in both univariate (Crude HR=0.36, P =0.01) and multivariate analysis ( P =0.01). In addition, lymphovascular invasion significantly increased risk in both univariate and multivariate analyses (adjusted HR=5.26, P <0.01). In conclusion, our study advocates for the early stratification of UC into IHC-based subtypes, facilitated by a panel of 4 markers, offering valuable insights into molecular characteristics, particularly in resource-constrained settings, and aiding clinical stratification.</p>","PeriodicalId":520562,"journal":{"name":"Applied immunohistochemistry & molecular morphology : AIMM","volume":" ","pages":"267-276"},"PeriodicalIF":1.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}