Histology and histopathology Vol.40,nº10 (2025)

Permanent URI for this collection

http://hdl.handle.net/10201/161669

Browse

Now showing 1 - 12 of 12

Open Access
Molecular pathology of adenoid cystic carcinoma
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Wei Shuanzeng; Pei Jianming; Zhang Paul J.L.; Biología Celular e Histología
Adenoid cystic carcinoma (ACC) is a slow-growing but locally aggressive salivary gland tumor. ACC is composed of ductal/tubular epithelial cells and basal/myoepithelial cells, which form cribriform, tubular, and solid growth patterns in variable combinations and dominance. ACC from different anatomic sites have similar morphological, molecular, and genetic changes. The key molecular alteration in ACC is chromosomal fusion/rearrangement/trans-location involving MYB or MYBL1, usually with NFIB as a fusion partner. In this review, we summarize the pathology and molecular alterations in ACC and their clinical significance
Open Access
Wnt5a regulates the expression of developmental genes in the adult retina following optic nerve crush injury
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Albano Gabrielle A.; Parrales Paola E.; Hackam Abigail S.; Biología Celular e Histología
Canonical and non-canonical Wnt signaling pathways are well-characterized regulators of retinal development. Wnt signaling also promotes neuro-protection and regeneration in adult tissues, including retinal ganglion cell (RGC) survival and axonal regrowth after optic nerve injury. However, it is unknown whether Wnt-dependent neuroprotection after injury in the adult CNS is associated with altered expression of developmental genes. Müller glia are a prominent radial glia type in the retina that play critical roles in retinal neuron protection, RGC neurite growth, and axon regeneration by acting through Wnt and other signaling pathways. We recently used mass spectrometry to characterize proteins secreted from Müller glia in response to Wnt signaling. In this study, we investigated whether the Wnt-induced Müller glia secretome includes proteins involved in development and whether their corresponding genes are regulated by Wnt5a during axonal regeneration in a mouse model of optic nerve crush (ONC) injury. Adult mice received intravitreal injections of Wnt5a or saline at the time of ONC injury, and then retina tissue was collected at early time points post-injury. The expression of candidate Wnt-regulated developmental genes and related proteins were characterized by qPCR and immunohistochemistry. Our findings revealed that Wnt5a downregulated the expression of specific developmental genes, including cilia-related genes Nphp4, INTU, and Jade1, as well as transcriptional regulators Pax6 and Tsc1, with time-dependent changes observed during axonal regrowth. Several of these genes were localized to RGCs and inner nuclear layer cells, suggesting direct effects in RGCs and contributions from Müller glia. These results demonstrate that specific developmental gene pathways are suppressed by Wnt5a in association with RGC survival and axon regrowth following injury. Therefore, this study adds to our knowledge of potential mechanisms of Wnt-mediated optic nerve regeneration and identifies new categories of putative regeneration-regulating genes for further study
Open Access
PLEKHG2 and the PLEKHG family: Linking Rho family GTPases to neural development and disorders
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Sato Katsuya; Nishikawa Masashi; Nagata Koh-ichi; Ueda Hiroshi; Biología Celular e Histología
Rho family small GTPases (Rho GTPases) are key regulators of cellular morphology, primarily through their control of the actin cytoskeleton. They play crucial roles in various cellular processes, including cell division, adhesion, and migration. The activity of Rho GTPases is tightly regulated by specific guanine nucleotide exchange factors (GEFs), which facilitate the exchange of GDP for GTP, thereby activating the GTPases. In the human genome, RhoGEFs are categorized into two major families: the DOCK family, comprising 11 members characterized by dedicator of cytokinesis (DOCK) homology regions, and the Dbl family, consisting of 64 members that contain a diffuse B-cell lymphoma (Dbl) homology domain. This review focuses on the pleckstrin homology and RhoGEF domain containing G (PLEKHG) family within the Dbl family of RhoGEFs, which remains largely un-characterized. We summarize their structure and function, with a particular emphasis on PLEKHG2, discussing its regulatory mechanisms, interactions with various molecules, and its involvement in neural functions
Open Access
Genomic features of bladder neuroendocrine carcinoma with composite histology
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Ohmoto Akihiro; Kitahama Keiichiro; Shigematsu Yasuyuki; Hayashi Naomi; Yonese Junji; Inamura Kentaro; Takahashi Shunji; Biología Celular e Histología
Neuroendocrine carcinoma (NEC) is a rare and aggressive malignancy derived from multiple body parts, with the urogenital organs being the second-largest extrapulmonary sites. The detailed mechanism of bladder NEC pathogenesis remains unknown. We reviewed data from 23 patients diagnosed with NEC from urogenital organs (bladder and prostate) and conducted targeted sequencing of 523 cancer-related genes, focusing on bladder NEC. While 14 cases featured a pure NEC histology, the remaining nine cases included NEC histology mixed with other tumors, such as urothelial carcinoma (UC) or adenocarcinoma. Median overall survival in the entire cohort was 11.1 months, and survival curves were comparable between pure NEC and NEC of mixed appearance. Major mutations detected in the NEC component were in TP53 (38%), TERT promoter (31%), PIK3CA (25%), histone-modification genes (19%), and RB1 (19%). The BARD1 frameshift variant related to homologous recombination was also detected in one patient. More than half of the patients had a high total mutational burden (TMB; ≥10), including two with a TMB ≥45. Intriguingly, at least one identical gene variant in driver genes was detected between NEC and non-NEC (UC) components in the four bladder specimens analyzed. These results highlight the possibility of shared genetic background between bladder NEC and UC. Additionally, several cases harbored druggable gene alterations as presented by TMB-high. Our presentation of the histopathologi-cal and molecular features of NEC may help clarify the underlying mechanisms and contribute to efficient treatment of the disease
Open Access
Liquid biopsy of circulating tumor cells: From isolation, enrichment, and genome sequencing to clinical applications
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Tan Keqin; Zhu Hong; Ma Xuelei; Biología Celular e Histología
Circulating tumor cells (CTCs), shed from primary tumors into the bloodstream, play a crucial role in metastasis and hold great potential in cancer diagnosis, prognosis, and treatment monitoring. Conventional CTC detection using epithelial biomarkers like epithelial cell adhesion molecule (EpCAM) for immunocapture overlooks mesenchymal-like CTCs with high metastatic potential, spurring the development of non-immunocapture technologies that use biophysical traits for enrichment. Innovations in microfluidic platforms and multi-parametric sorting improve isolation efficiency and address related challenges. Breakthroughs in single-cell genomic and transcriptomic sequencing enable in-depth molecular characterization of CTCs. Clinically, CTC enumeration and molecular profiling are emerging as real-time tools for assessing therapeutic response and predicting outcomes, especially in metastatic breast, prostate, and colorectal cancers. This review focuses on CTC isolation, enrichment techniques, their applications in different tumors, downstream analysis progress, and potential in precision medicine
Open Access
The prognostic value of adipokine receptors leptinR and adiponectinR1 in obesity-inducible solid tumours
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Bernhardt, Marit; Thiesler, Thore; Winterhagen, Franziska Isabelle; Türler, Andreas; Ritter, Manuel; Mustea, Alexander; Kristiansen, Glen; Bollen, Isabella; Biología Celular e Histología
Background. With the rising incidence of life expectancy, obesity, and tumours, understanding the incretory influence of adipose tissue in tumorigenesis becomes increasingly important. As the adipokines leptin and adiponectin are released by fat tissue, we aimed to analyse the expression of their respective receptors in tumours for which an association with obesity is epidemiologically hypothesised. Methods. The expression of leptinR and adipoR1 were analysed in cohorts of renal cell cancer (n=391), cervical cancer (n=155), vulvar cancer (n=107), and endometrial cancer (n=90) by immunohistochemistry and correlated with clinicopathological parameters including survival times. Results. Expression of leptinR was high in renal cell cancer (62.2%), vulvar carcinoma (50%), and endometrial cancer (80.5%). High expression was associated with favourable clinico-pathological markers and longer overall survival times in renal cell and vulvar cancer. AdipoR1 was only weakly expressed in all four tumour entities and did not show significant associations with clinicopathological parameters or prognosis. Conclusion. High leptinR is a promising biomarker of favourable tumour outcomes in renal cell carcinoma and vulvar carcinoma.
Open Access
Suppressive role of fukutin on cell proliferation in uterine cervical carcinoma in relation to Aurora-A kinase
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Yamamoto Tomoko; Okamura Yukinori; Kato Yoichiro; Masui Kenta; Nagasima Yoji; Kurata Atsushi; Biología Celular e Histología
Fukutin, the gene responsible for Fukuyama congenital muscular dystrophy (FCMD), is involved in the glycosylation of α-dystroglycan (α-DG). On the other hand, fukutin is expressed in various organs, and the roles of fukutin in non-neuromuscular tissues are not fully elucidated. In the present immunohistochemical study of uterine cervical carcinoma, Ki-67-positive cells tended to be more in areas showing weaker expression of fukutin. In HeLa cells, Ki-67-positive cells were increased after the suppression of fukutin by RNAi, and were decreased by overexpression of fukutin. Similar results were obtained upon phosphorylation of histone H3 at serine 10, which is enriched during mitosis. Interestingly, Aurora-A kinase (AURKA), one of the proteins regulating Ser10 phosphorylation of histone H3, was highly expressed in HeLa cells, and the phosphorylation of AURKA was reduced by overexpression of fukutin. Furthermore, fukutin is co-localized with targeting protein for Xklp2 (TPX2), a protein enhancing AURKA activity. Fukutin may be able to suppress cell proliferation by reducing AURKA phosphorylation, probably competing with TPX2
Open Access
Galangin alleviates gastric mucosal injury in rats with chronic atrophic gastritis by reducing ferroptosis
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Yang Tian; Lu Min; Jiang Weiqiang; Jin Dandan; Sun Meiling; Mao Hua; Han Huixia; Biología Celular e Histología
Objective. Chronic atrophic gastritis (CAG) is a precancerous lesion and is the first stage in a multistep precancerous cascade that can lead to gastric adenocarcinoma. This study aimed to reveal the role and mechanism of galangin in CAG. Methods. Rats were intragastrically administered a mixture of 2% sodium salicylate and 30% alcohol, forced to exercise, and fasted irregularly to establish CAG models. To explore the efficacy of galangin on CAG rats, we used Hericium erinaceus (HE) and omeprazole (Ome) as controls. The degree of gastric mucosal injury was assessed by H&E staining and immunohistochemistry. Perls staining and western blot analysis were used to assess iron content and enrichment of ferroptosis-related proteins. Reactive oxygen species and mitochondrial superoxide in the mucosa were visualized by probes. The morphology of cells was examined by transmission electron microscopy. Results. Our data showed that galangin treatment alleviated gastric mucosal damage and reduced ferroptosis in CAG rats, manifested as decreased iron content, iron transporters and storage proteins, decreased ROS and mitochondrial superoxide, and partially restored cellular morphology. Of note, galangin at a high concentration had better treatment efficacy than HE but lower than Ome. Conclusions. This study demonstrated that galangin reduced gastric mucosal injury in CAG rats by inhibiting ferroptosis. These findings provide a theoretical basis for its clinical application and broaden its potential applications
Open Access
Shensiqigui tablets alleviate bleomycin-induced pulmonary fibrosis by inhibiting the hedgehog/wnt-β-catenin pathway
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Ma Rui; Xie Yupeng; Dong Yuan; Yin Fan; Yang Jiong; Xu Fenghua; Biología Celular e Histología
Background. Pulmonary fibrosis (PF) is a refractory disease characterized by inflammation and fibrosis. Shensiqigui Tablets (SSQGT), a combination of Codonopsis pilosula, Astragalus, and Angelica, is a traditional Chinese medicine with anti-inflammatory and antioxidant properties. Therefore, SSQGT may be a potential therapeutic agent for managing PF. This study aimed to investigate the effects of SSQGT on PF and its potential mechanisms. Methods. This study established a mouse model of PF through a single intratracheal injection of bleomycin (BLM) and used a TGF-β1-induced HFL-1 cell model. The experiment included control, model (BLM/TGF-β1), and treatment groups (pirfenidone, compound Biejiaruangan tablet (BJRGT), low-dose SSQGT, medium-dose SSQGT, and high-dose SSQGT). Histopathological changes and collagen deposition in lung tissues were observed using Hematoxylin-Eosin (HE) and Masson staining. Inflammatory exudation in bronchoalveolar lavage fluid (BALF) was assessed using ELISA, including TNF-α, IL-1β, IL-6, and NO. Oxidative stress markers SOD, GSH, and Malondi-aldehyde (MDA) were measured using commercial kits. mRNA and protein expression levels in lung tissues and in vitro models, including α-SMA, vimentin, collagen I, caspase-3, TGF-β, and the Hedgehog/Wnt-β-catenin pathway, were evaluated using qRT-PCR and western blot analysis. Results. SSQGT significantly alleviated BLM-induced weight loss and lung injury in mice and reduced HYP levels and collagen deposition. Additionally, SSQGT improved oxidative stress markers (decreased MDA levels and increased SOD and GSH activity) and mitigated inflammatory responses (reduced TNF-α, IL-1β, IL-6, and NO levels) and (downregulated α-SMA, collagen I, caspase-3, and TGF-β). Further mechanistic analysis showed that SSQGT inhibited the Hedgehog/ Wnt-β-catenin pathway. Conclusion. SSQGT alleviates BLM- or TGF-β1-induced PF by reducing oxidative stress and inhibiting inflammation through the suppression of the Hedgehog/ Wnt-β-catenin pathway, suggesting its potential as a therapeutic agent for PF
Open Access
Advantages and limitations of 3,3',5,5'-tetramethylbenzidine for immunohistochemical staining
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Yu Chao; Liu Xiao; Zhao Peiyuan; Sun Zhidong; Song Yurong; Cao Yuan; Cheng Ming; Biología Celular e Histología
In this study, two chromogenic systems, horseradish peroxidase (HRP)-3,3’-diaminobenzidine (DAB) and HRP-3,3',5,5'-tetramethylbenzidine (TMB), were used to perform single-color and double-color immunohistochemical staining (sIHC and dIHC, respectively) on multiple antigens in four distinct tissue types. The chromogenic results of the HRP-TMB system exhibited a vibrant blue-green color, and the tissue localization and signal intensity were consistent with those of the HRP-DAB system. In addition, it demonstrated clear differentiation from the hematoxylin-stained nucleus, endogenous melanin, and brown chromogenic results of HRP-DAB. TMB staining in tissues that contain high endogenous pigment levels eliminates the need for melanin bleaching, thereby facilitating direct observation and potentially improving the detection speed and interpretation. TMB can also be used in combination with DAB for dIHC, thus allowing detection of the two markers on a single slide. However, the TMB staining results are not stable over the long term and require image storage using slide scanners, thereby limiting its application. Additionally, in dIHC, overlapping signals of the first marker may obscure the second marker, potentially leading to bias or false negatives. Therefore, careful consideration is required when designing dIHC detection systems. Based on the above, we propose that TMB is a valuable supplement to DAB for immunohistochemical staining and deserves further promotion and utilization. However, additional research is needed to improve the composition of TMB chromogenic reagents, prolong the longevity of staining results, and overcome current limitations
Open Access
Oxidative stress markers 8-OHdG, Trx-1, and Prx6 are expressed in seminoma and are connected to TXNDC2, 3, and 6 expression levels
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Rantala Inka; Teppo Hanna-Riikka; Händelin Jonas; Kemppainen Janette; Ollikainen Riina K.; Kuittinen Outi; Kuusisto Milla E.L.; Biología Celular e Histología
Testis-specific thioredoxins (TXNDCs) and oxidative stress have not been studied before in seminoma. We studied the immunohistochemical (IHC) expression of 8-OHdG, Prx6, Trx-1, TXNDC2, 3, and 6 in 25 testicular seminoma and 24 control samples. We retrospectively collected patient details and treatments from hospital records and combined them with IHC results. In normal testis, IHC expression of 8-OHdG, Prx6, TXNDC2, and 3 was higher than in seminoma samples (p<0.001 each), and the absence of n8-OHdG (p=0.002) and nTXNDC2 expression (p=0.044) was clinically associated with elevated lactate dehydrogenase levels. On the contrary, Trx-1 and TXNDC6 were over-expressed in seminoma samples (p=0.035 and p<0.001, respectively), and TXNDC6 was negatively associated with age over 40 (p=0.036). Concordant with the IHC expression, PRDX6 mRNA levels were downregulated with a fold change of -2517.4 (p<0.001), and TXN mRNA levels were upregulated with a fold change of 11637.4 (p=0.008) in seminoma samples compared with healthy controls. The oxidative stress markers studied had a correlation between the nuclear and cytoplasmic localization, a mutual correlation in expression between different markers, and mutual protein-protein interactions according to STRING Enrichment analysis. Our results show that oxidative stress markers and their expression in seminoma differ from that in normal testis tissue. Trx-1 and cTXNDC6 are seemingly overexpressed in seminoma, which might indicate their relevance in seminoma biology
Open Access
NTRK protein expression in NSCLC and its clinicopathological correlation
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Gutierrez Herrera Jair; Montero Fernandez M. Angeles; De Petris Luigi; Guijarro Ricardo; Ekman Simon; Ortiz Villalón Cristian; Biología Celular e Histología
Non-small cell lung cancer (NSCLC) is a complex disease with diverse clinical and molecular characteristics. Since the discovery of the oncogenic neurotrophic receptor tyrosine kinase (NTRK) gene fusion in colorectal cancer in 1986, its understanding has gradually progressed. NTRK’s relevance is crucial to understanding some tumor development and how specific tyrosine receptor kinase inhibitors (TRKI) work. NTRK1, NTRK2, and NTRK3 (encoding the neurotrophin receptors TRKA, TRKB, and TRKC, respectively) rearrangement induces high tumor transforming ability. This study investigates the clinical relevance of NTRK immunohistochemistry in NSCLC patients in a cohort of 482 patients from Karolinska University Hospital with detailed clinical and pathological studies. Immunohistochemical staining for NTRK expression was performed, and the results were correlated with patient demographics, histological subtypes, tumor extent, and staging. Our findings revealed that NTRK expression, predominantly membranous and cytoplasmic, was detected in 22 out of 482 cases (4.56%). Notably, NTRK expression was more frequently observed in squamous-cell carcinoma (SqCC) than in adenocarcinoma (AdCa). Clinical correlations indicated a significant association between NTRK expression and histologic subtypes (p<0.001) and grade of differentiation (p=0.036). However, no significant correlations were observed with age, sex, tumor size, staging, or OS. NTRK immunohistochemistry represents a potential biomarker for a subset of NSCLC patients, particularly those with SqCC histology. Understanding the clinical implications of NTRK expression may contribute to personalized treatment strategies in NSCLC

Browse

Browsing Histology and histopathology Vol.40,nº10 (2025) by Issue Date

Results Per Page

Sort Options