Journal of Pathology Clinical Research最新文献

{"title":"Digital image analysis allows objective stratification of patients with silent PIT1-lineage pituitary neuroendocrine tumors","authors":"Jiangyan Zhao,&nbsp;Chenxing Ji,&nbsp;Haixia Cheng,&nbsp;Zhen Ye,&nbsp;Boyuan Yao,&nbsp;Ming Shen,&nbsp;Xuefei Shou,&nbsp;Xiang Zhou,&nbsp;Hongying Ye,&nbsp;Zhaoyun Zhang,&nbsp;Hong Chen,&nbsp;Yongfei Wang,&nbsp;Fuchu He,&nbsp;Yao Zhao,&nbsp;Wei Gong,&nbsp;Qilin Zhang,&nbsp;Nidan Qiao","doi":"10.1002/cjp2.340","DOIUrl":"10.1002/cjp2.340","url":null,"abstract":"<p>Studies describing the clinical presentation and prognosis of patients with silent PIT1 (pituitary specific transcription factor)-lineage pituitary neuroendocrine tumors (PitNETs) are rare. We identified patients with positive PIT1 tumor staining but without evidence of hormone hypersecretion at a tertiary center. Clusters were obtained according to cell morphology and immunostaining from each patient's digitally segmented whole slide image. We compared the clinical presentations, radiological features, and prognoses of the different clusters. We identified 146 patients (68 male, 42.9 ± 14.1 years old) with silent PIT1-lineage PitNETs. Morphology clustering suggested that tumors with large nuclei and apparent eccentricity were associated with a higher proportion of aggressiveness and a higher hazard of recurrence [hazard ratio (HR): 2.64, (95% CI, 1.06–6.55), <i>p</i> = 0.037]. Immunohistochemical clustering suggested that tumors with thyroid stimulating hormone (TSH) staining or all negative PIT1-lineage hormones were associated with a higher proportion of aggressiveness and a higher risk of recurrence [HR: 12.4, (95% CI, 1.60–93.5), <i>p</i> = 0.015]. We obtained three-tier risk profiles by combining morphological and immunohistochemical clustering. Patients with the high-risk profile presented the highest recurrence rate compared with those in the medium-risk and low-risk profiles [HR: 3.54, (95% CI, 1.40–8.93), <i>p</i> = 0.002]. In conclusion, digital image analysis based on cell morphology and immunohistochemical staining allows objective stratification of patients with silent PIT1-lineage tumors. Typical morphological characteristics of high-risk tumors are large tumor nuclei and high eccentricity, and typical immunostaining characteristics are TSH staining or negative staining for all PIT1-lineage hormones.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"9 6","pages":"488-497"},"PeriodicalIF":4.1,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cjp2.340","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10500273","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":"Reducing the risks of nuclear war – the role of health professionals","authors":"K. Abbasi, Parveen Ali, Virginia Barbour, Kirsten Bibbins-Domingo, Marcel G M Olde Rikkert, Andy Haines, Ira Helfand, R. Horton, Bob Mash, A. Mitra, C. Monteiro, E. Naumova, E. J. Rubin, Tilman Ruff, P. Sahni, J. Tumwine, Paul Yonga, Chris Zielinski","doi":"10.54079/jpmi.37.3.3291","DOIUrl":"https://doi.org/10.54079/jpmi.37.3.3291","url":null,"abstract":"Kamran Abbasi, Parveen Ali , Virginia Barbour , Kirsten Bibbins-Domingo , Marcel GM Olde Rikkert , Andy Haines , Ira Helfand, Richard Horton , Bob Mash , Arun Mitra, Carlos Monteiro , Elena N Naumova , Eric J Rubin , Tilman Ruff, Peush Sahni , James Tumwine , Paul Yonga and Chris Zielinski* British Medical Journal, London, UK International Nursing Review, Sheffield, UK Medical Journal of Australia, Brisbane, Australia JAMA, San Francisco, CA, USA Dutch Journal of Medicine, Nijmegen, The Netherlands London School of Hygiene and Tropical Medicine, London, UK International Physicians for the Prevention of Nuclear War, Springfield, IL, USA The Lancet, London, UK African Journal of Primary Health Care & Family Medicine, Stellenbosch, South Africa International Physicians for the Prevention of Nuclear War, Ludhiana, India Revista de Saúde Pública, São Paulo, Brazil Journal of Public Health Policy, Boston, MA, USA New England Journal of Medicine, Cambridge, MA, USA International Physicians for the Prevention of Nuclear War, Melbourne, Australia National Medical Journal of India, New Delhi, India African Health Sciences, Kampala, Uganda East African Medical Journal, Nairobi, Kenya University of Winchester, Winchester, UK","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"9 1","pages":"439 - 441"},"PeriodicalIF":4.1,"publicationDate":"2023-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44772171","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":"Translational practice of fluorescence in situ hybridisation to identify neuroblastic tumours with TERT rearrangements","authors":"Yongbo Yu,&nbsp;Meng Zhang,&nbsp;Xingfeng Yao,&nbsp;Xiaoxing Guan,&nbsp;Chao Jia,&nbsp;Ping Chu,&nbsp;Ruqian Zhang,&nbsp;Yeran Yang,&nbsp;Yaqiong Jin,&nbsp;Huanmin Wang,&nbsp;Xin Ni,&nbsp;Lejian He,&nbsp;Yongli Guo","doi":"10.1002/cjp2.338","DOIUrl":"10.1002/cjp2.338","url":null,"abstract":"<p>Recently, <i>telomerase reverse transcriptase</i> (<i>TERT</i>) gene rearrangements have been identified in neuroblastoma (NB), the typical pathological type of neuroblastic tumours (NTs); however, the prevalence of <i>TERT</i> rearrangements in other types of NT remains unknown. This study aimed to develop a practical method for detecting <i>TERT</i> defects and to evaluate the clinical relevance of <i>TERT</i> rearrangements as a biomarker for NT prognosis. A <i>TERT</i> break-apart probe for fluorescence <i>in situ</i> hybridisation (FISH) was designed, optimised, and applied to assess the genomic status of <i>TERT</i> in Chinese children with NTs at the Beijing Children's Hospital from 2016 to 2019. Clinical, histological, and genetic characteristics of <i>TERT</i>-rearranged NTs were further addressed. Genomic <i>TERT</i> rearrangements could be effectively detected by FISH and were mutually exclusive with <i>MYCN</i> amplification. <i>TERT</i> rearrangements were identified in 6.0% (38/633) of NTs overall, but 12.4% (31/250) in high-risk patients. <i>TERT</i> rearrangements identified a subtype of aggressive NTs with the characteristics of Stage 3/4, high-risk category, over 18 months old, and presenting all histological subtypes of NB and ganglioneuroblastoma nodular. Moreover, <i>TERT</i> rearrangements were significantly associated with elevated <i>TERT</i> expression levels and decreased survival chances. Multivariable analysis confirmed that it was an independent prognostic marker for NTs. FISH is an easily applicable method for evaluating <i>TERT</i> defects, which define a subgroup of NTs with unfavourable prognosis. <i>TERT</i> rearrangements would contribute to characterising NT molecular signatures in clinical practice.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"9 6","pages":"475-487"},"PeriodicalIF":4.1,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/e3/CJP2-9-475.PMC10556277.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10052195","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":"High expression of insulinoma-associated protein 1 (INSM1) distinguishes colorectal mixed and pure neuroendocrine carcinomas from conventional adenocarcinomas with diffuse expression of synaptophysin","authors":"Anne-Sophie Litmeyer,&nbsp;Björn Konukiewitz,&nbsp;Atsuko Kasajima,&nbsp;Sebastian Foersch,&nbsp;Felix Schicktanz,&nbsp;Maxime Schmitt,&nbsp;Franziska Kellers,&nbsp;Albert Grass,&nbsp;Paul Jank,&nbsp;Bettina Lehman,&nbsp;Thomas M Gress,&nbsp;Anja Rinke,&nbsp;Detlef K Bartsch,&nbsp;Carsten Denkert,&nbsp;Wilko Weichert,&nbsp;Günter Klöppel,&nbsp;Moritz Jesinghaus","doi":"10.1002/cjp2.339","DOIUrl":"10.1002/cjp2.339","url":null,"abstract":"<p>Complementary to synaptophysin and chromogranin A, insulinoma-associated protein 1 (INSM1) has emerged as a sensitive marker for the diagnosis of neuroendocrine neoplasms. Since there are no comparative data regarding INSM1 expression in conventional colorectal adenocarcinomas (CRCs) and colorectal mixed adenoneuroendocrine carcinomas/neuroendocrine carcinomas (MANECs/NECs), we examined INSM1 in a large cohort of conventional CRCs and MANECs/NECs. In conventional CRC, we put a special focus on conventional CRC with diffuse expression of synaptophysin, which carry the risk of being misinterpreted as a MANEC or a NEC. We investigated INSM1 according to the immunoreactive score in our main cohort of 1,033 conventional CRCs and 21 MANECs/NECs in comparison to the expression of synaptophysin and chromogranin A and correlated the results with clinicopathological parameters and patient survival. All MANECs/NECs expressed INSM1, usually showing high or moderate expression (57% high, 34% moderate, and 9% low), which distinguished them from conventional CRCs, which were usually INSM1 negative or low, even if they diffusely expressed synaptophysin. High expression of INSM1 was not observed in conventional CRCs. Chromogranin A was negative/low in most conventional CRCs (99%), but also in most MANECs/NECs (66%). Comparable results were observed in our independent validation cohorts of conventional CRC (<i>n</i> = 274) and MANEC/NEC (<i>n</i> = 19). Similar to synaptophysin, INSM1 expression had no prognostic relevance in conventional CRCs, while true MANEC/NEC showed a highly impaired survival in univariate and multivariate analyses (e.g. disease-specific survival: <i>p</i> &lt; 0.001). MANECs/NECs are a highly aggressive variant of colorectal cancer, which must be reliably identified. High expression of INSM1 distinguishes MANEC/NEC from conventional CRCs with diffuse expression of the standard neuroendocrine marker synaptophysin, which do not share the same dismal prognosis. Therefore, high INSM1 expression is a highly specific/sensitive marker that is supportive for the diagnosis of true colorectal MANEC/NEC.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"9 6","pages":"498-509"},"PeriodicalIF":4.1,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/be/0b/CJP2-9-498.PMC10556265.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10053769","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":"DNA methylation profile discriminates sporadic giant cell granulomas of the jaws and cherubism from their giant cell-rich histological mimics","authors":"Letícia Martins Guimarães,&nbsp;Daniel Baumhoer,&nbsp;Vanghelita Andrei,&nbsp;Dennis Friedel,&nbsp;Christian Koelsche,&nbsp;Ricardo Santiago Gomez,&nbsp;Andreas von Deimling,&nbsp;Carolina Cavalieri Gomes","doi":"10.1002/cjp2.337","DOIUrl":"10.1002/cjp2.337","url":null,"abstract":"<p>Sporadic giant cell granulomas (GCGs) of the jaws and cherubism-associated giant cell lesions share histopathological features and microscopic diagnosis alone can be challenging. Additionally, GCG can morphologically closely resemble other giant cell-rich lesions, including non-ossifying fibroma (NOF), aneurysmal bone cyst (ABC), giant cell tumour of bone (GCTB), and chondroblastoma. The epigenetic basis of these giant cell-rich tumours is unclear and DNA methylation profiling has been shown to be clinically useful for the diagnosis of other tumour types. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic GCG and cherubism to test whether DNA methylation patterns can help to distinguish them. Additionally, we compared the DNA methylation profile of these lesions with those of other giant cell-rich mimics to investigate if the microscopic similarities extend to the epigenetic level. DNA methylation analysis was performed for central (<i>n</i> = 10) and peripheral (<i>n</i> = 10) GCG, cherubism (<i>n</i> = 6), NOF (<i>n</i> = 10), ABC (<i>n</i> = 16), GCTB (<i>n</i> = 9), and chondroblastoma (<i>n</i> = 10) using the Infinium Human Methylation EPIC Chip. Central and peripheral sporadic GCG and cherubism share a related DNA methylation pattern, with those of peripheral GCG and cherubism appearing slightly distinct, while central GCG shows overlap with both of the former. NOF, ABC, GCTB, and chondroblastoma, on the other hand, have distinct methylation patterns. The global and enhancer-associated CpG DNA methylation values showed a similar distribution pattern among central and peripheral GCG and cherubism, with cherubism showing the lowest and peripheral GCG having the highest median values. By contrast, promoter regions showed a different methylation distribution pattern, with cherubism showing the highest median values. In conclusion, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism-associated giant cell lesions. Conversely, it could discriminate sporadic GCG of the jaws from their giant cell-rich mimics (NOF, ABC, GCTB, and chondroblastoma).</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"9 6","pages":"464-474"},"PeriodicalIF":4.1,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/51/CJP2-9-464.PMC10556276.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10332289","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":"RAD51 as a biomarker for homologous recombination deficiency in high-grade serous ovarian carcinoma: robustness and interobserver variability of the RAD51 test","authors":"Claire JH Kramer,&nbsp;Alba Llop-Guevara,&nbsp;Elisa Yaniz-Galende,&nbsp;Benedetta Pellegrino,&nbsp;Natalja T ter Haar,&nbsp;Andrea Herencia-Ropero,&nbsp;Nicoletta Campanini,&nbsp;Antonino Musolino,&nbsp;Tjalling Bosse,&nbsp;Alexandra Leary,&nbsp;Violeta Serra,&nbsp;Maaike PG Vreeswijk","doi":"10.1002/cjp2.336","DOIUrl":"10.1002/cjp2.336","url":null,"abstract":"<p>The RAD51 test is emerging as a promising biomarker for the assessment of functional homologous recombination deficiency (HRD). Yet, the robustness and reproducibility of the immunofluorescence-based RAD51 test, in different academic laboratories, have not been systematically investigated. Therefore, we tested the performance of the RAD51 assay in formalin-fixed paraffin-embedded (FFPE) high-grade serous ovarian carcinoma (HGSOC) samples in four European laboratories. Here, we confirm that subtle differences in staining procedures result in low variability of RAD51 and γH2AX scores. However, substantial variability in RAD51 scoring was observed in some samples, likely due to complicating technical and biological features, such as high RAD51 signal-to-noise ratio and RAD51 heterogeneity. These results support the need to identify and perform additional quality control steps and/or automating image analysis. Altogether, resolving technical issues should be a priority, as identifying tumours with functional HRD is urgently needed to guide the individual treatment of HGSOC patients. Follow-up studies are needed to define the key tissue quality requirements to assess HRD by RAD51 in FFPE tumour samples, as this test could help in guiding the individual treatment of HGSOC patients.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"9 6","pages":"442-448"},"PeriodicalIF":4.1,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/64/14/CJP2-9-442.PMC10556259.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10242543","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":"The epigenetic modifier lysine methyltransferase 2C is frequently mutated in gastric remnant carcinoma","authors":"Bo Sun,&nbsp;Haojie Chen,&nbsp;Jiawen Lao,&nbsp;Cong Tan,&nbsp;Yue Zhang,&nbsp;Zhen Shao,&nbsp;Dazhi Xu","doi":"10.1002/cjp2.335","DOIUrl":"10.1002/cjp2.335","url":null,"abstract":"<p>Gastric remnant carcinoma (GRC), which occurs in the stomach after partial gastrectomy, is a rare and aggressive form of gastric adenocarcinoma (GAC). Comprehensive profiling of genomic mutations in GRC could provide the basis for elucidating the origin and characteristics of this cancer. Herein, whole-exome sequencing (WES) was performed on 36 matched tumor–normal samples from patients with GRC and identified recurrent mutations in epigenetic modifiers, notably <i>KMT2C</i>, <i>ARID1A</i>, <i>NSD1</i>, and <i>KMT2D</i>, in 61.11% of cases. Mutational signature analysis revealed a low frequency of microsatellite instability (MSI) in GRC, which was further identified by MSIsensor, MSI-polymerase chain reaction, and immunohistochemistry analysis. Comparative analysis demonstrated that GRC had a distinct mutation spectrum compared to that of GAC in The Cancer Genome Atlas samples, with a significantly higher mutation rate of <i>KMT2C</i>. Targeted deep sequencing (Target-seq) of an additional 25 paired tumor–normal samples verified the high mutation frequency (48%) of <i>KMT2C</i> in GRC. <i>KMT2C</i> mutations correlated with poor overall survival in both WES and Target-seq cohorts and were independent prognosticators in GRC. In addition, <i>KMT2C</i> mutations were positively correlated with favorable outcomes in immune checkpoint inhibitor-treated pan-cancer patients and associated with higher intratumoral CD3⁺, CD8⁺ tumor-infiltrating lymphocyte counts, and PD–L1 expression in GRC samples (<i>p</i> = 0.018, 0.092, 0.047, 0.010, and 0.034, respectively). Our dataset provides a platform for information and knowledge mining of the genomic characteristics of GRC and helps to frame new therapeutic approaches for this disease.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"9 5","pages":"409-422"},"PeriodicalIF":4.1,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c1/7e/CJP2-9-409.PMC10397379.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9960626","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":"Cancer-associated fibroblast expression of glutamine fructose-6-phosphate aminotransferase 2 (GFPT2) is a prognostic marker in gastric cancer","authors":"Shuo Yang,&nbsp;Guoli Li,&nbsp;Xin Yin,&nbsp;Yufei Wang,&nbsp;Xinju Jiang,&nbsp;Xiulan Bian,&nbsp;Tianyi Fang,&nbsp;Shengjie Yin,&nbsp;Lei Zhang,&nbsp;Yingwei Xue","doi":"10.1002/cjp2.333","DOIUrl":"10.1002/cjp2.333","url":null,"abstract":"<p>Glutamine fructose-6-phosphate aminotransferase 2 (GFPT2) is a rate-limiting enzyme in hexosamine biosynthesis involved in the occurrence and progress of many cancers. What role it plays in gastric cancer (GC) is still unclear. In this study, transcriptome sequencing data from the Harbin Medical University (HMU)-GC cohort and The Cancer Genome Atlas (TCGA) dataset were combined with the HMU-TCGA training cohort to analyze the biological function and clinical significance of <i>GFPT2</i>. The correlation of <i>GFPT2</i> with immune cells and stromal cells was analyzed in the GC immune microenvironment through transcriptome sequencing data and a public single-cell sequencing database. In cell lines, GC tissues, and the tissue microarray, GFPT2 protein expression was confirmed by western blotting and immunohistochemistry. The mRNA of <i>GFPT2</i> was highly expressed in the tumor (<i>p</i> &lt; 0.001), and GC cells and tumors expressed high levels of GFPT2 protein. Compared to low expression, high <i>GFPT2</i> mRNA expression was associated with higher levels of tumor invasion, higher pathological stages, and poor prognosis (<i>p</i> = 0.02) in GC patients. In a drug susceptibility analysis, <i>GFPT2</i> mRNA expression was associated with multiple chemotherapeutic drug sensitivity, including docetaxel, paclitaxel, and cisplatin. Gene enrichment analysis found that <i>GFPT2</i> was mainly primarily involved in the extracellular matrix receptor interaction pathway. The ESTIMATE, CIBERSORT, and ssGSEA algorithms showed that <i>GFPT2</i> was associated with immune cell infiltration. In addition, <i>GFPT2</i> was more likely to be expressed within cancer-associated fibroblasts (CAFs), and high levels of <i>GFPT2</i> expression were highly correlated with four CAFs scores (all <i>p</i> &lt; 0.05). Finally, a prognostic model to assess the risk of death in GC patients was constructed based on GFPT2 protein expression and lymph node metastasis rate. In conclusion, GFPT2 plays an essential role in the function of CAFs in GC. It can be used as a biomarker to assess GC prognosis and immune infiltration.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"9 5","pages":"391-408"},"PeriodicalIF":4.1,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ca/d6/CJP2-9-391.PMC10397376.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9960627","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":"Exosome-derived ANXA9 functions as an oncogene in breast cancer","authors":"Cuiping Lu,&nbsp;Ying Zhan,&nbsp;Yunshan Jiang,&nbsp;Jianrong Liao,&nbsp;Zidan Qiu","doi":"10.1002/cjp2.334","DOIUrl":"10.1002/cjp2.334","url":null,"abstract":"<p>Breast cancer (BCA) is one of the most prevalent cancers among women. Emerging evidence has revealed that Annexin A-9 (<i>ANXA9</i>) plays a crucial function in the development of some cancers. Notably, <i>ANXA9</i> has been reported to be a new prognostic biomarker for gastric and colorectal cancers. However, its expression and biological function in BCA have not yet been investigated. Using online bioinformatics tools such as TIMER, GEPIA, HPA, and UALCAN, we predicted <i>ANXA9</i> expression and its correlation with the clinicopathological characteristics of BCA patients. RT-qPCR and western blot were utilized to measure <i>ANXA9</i> mRNA and ANXA9 protein expression in BCA patient tissues and cells. BCA-derived exosomes were identified by transmission electron microscopy. Functional assays were employed to evaluate the biological role of <i>ANXA9</i> in BCA cell proliferation, migration, invasion, and apoptosis. A tumor xenograft <i>in vivo</i> model was utilized to assess the role of <i>ANXA9</i> in tumor growth in mice. Bioinformatics and functional screening analysis revealed that <i>ANXA9</i> was highly expressed in BCA patient tissues, with median <i>ANXA9</i> expression 1.5- to 2-fold higher than in normal tissues (<i>p</i> &lt; 0.05). RT-qPCR confirmed that <i>ANXA9</i> expression in BCA tissues was around 1.5-fold higher than the adjacent normal tissues (<i>p</i> &lt; 0.001). <i>ANXA9</i> expression in different subtypes of BCA also showed a difference, and <i>ANXA9</i> was found to be mostly significantly upregulated in luminal BCA relative to normal tissues or other histological subtypes (<i>p</i> &lt; 0.001). Moreover, <i>ANXA9</i> expression was elevated in different races, ages, clinical stages, node metastasis status, and menopause status groups relative to the normal group (<i>p</i> &lt; 0.001). Furthermore, <i>ANXA9</i> was found to be secreted by BCA tissue-derived exosomes and its expression was upregulated 1- to 7-fold in BCA cells treated with exosomes (<i>p</i> &lt; 0.001), while its expression in MCF10A cells was not significantly altered by treatment with exosomes (<i>p</i> &gt; 0.05). <i>ANXA9</i> silencing induced a significant decrease of around 30% in the colony number of BCA cells (<i>p</i> &lt; 0.01). The number of migrated and invaded BCA cells also decreased by around 65 and 68%, respectively, after silencing <i>ANXA9</i> (<i>p</i> &lt; 0.01). Tumor size was significantly reduced (nearly half) in the LV-sh-<i>ANXA9</i> group relative to the LV-NC group in the xenograft model (<i>p</i> &lt; 0.01), suggesting that <i>ANXA9</i> silencing repressed tumor progression in BCA progression <i>in vitro</i> and <i>in vivo</i>. In conclusion, exosome-derived <i>ANXA9</i> functions as an oncogene that facilitates the proliferation, migration, and invasiveness of BCA cells and enhances tumor growth in BCA development, which may provide a new prognostic and therapeutic biomarker for BCA patients.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"9 5","pages":"378-390"},"PeriodicalIF":4.1,"publicationDate":"2023-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pathsocjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cjp2.334","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9959583","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":"Post-operative mortality and recurrence patterns in pancreatic cancer according to KRAS mutation and CDKN2A, p53, and SMAD4 expression","authors":"Yohei Masugi,&nbsp;Manabu Takamatsu,&nbsp;Mariko Tanaka,&nbsp;Kensuke Hara,&nbsp;Yosuke Inoue,&nbsp;Tsuyoshi Hamada,&nbsp;Tatsunori Suzuki,&nbsp;Junichi Arita,&nbsp;Yuki Hirose,&nbsp;Yoshikuni Kawaguchi,&nbsp;Yousuke Nakai,&nbsp;Atsushi Oba,&nbsp;Naoki Sasahira,&nbsp;Gaku Shimane,&nbsp;Tsuyoshi Takeda,&nbsp;Keisuke Tateishi,&nbsp;Sho Uemura,&nbsp;Mitsuhiro Fujishiro,&nbsp;Kiyoshi Hasegawa,&nbsp;Minoru Kitago,&nbsp;Yu Takahashi,&nbsp;Tetsuo Ushiku,&nbsp;Kengo Takeuchi,&nbsp;Michiie Sakamoto,&nbsp;for the GTK Pancreatic Cancer Study Group in Japan","doi":"10.1002/cjp2.323","DOIUrl":"10.1002/cjp2.323","url":null,"abstract":"<p>Alterations in <i>KRAS</i>, <i>CDKN2A</i> (<i>p16</i>), <i>TP53</i>, and <i>SMAD4</i> genes have been major drivers of pancreatic carcinogenesis. The clinical course of patients with pancreatic cancer in relation to these driver alterations has not been fully characterised in large populations. We hypothesised that pancreatic carcinomas with different combinations of <i>KRAS</i> mutation and aberrant expression of CDKN2A, p53, and SMAD4 might show distinctive recurrence patterns and post-operative survival outcomes. To test this hypothesis, we utilised a multi-institutional cohort of 1,146 resected pancreatic carcinomas and assessed <i>KRAS</i> mutations by droplet digital polymerase chain reaction and CDKN2A, p53, and SMAD4 expression by immunohistochemistry. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were computed according to each molecular alteration and the number of altered genes using the Cox regression models. Multivariable competing risks regression analyses were conducted to assess the associations of the number of altered genes with specific patterns of recurrence. Loss of SMAD4 expression was associated with short DFS (multivariable HR, 1.24; 95% CI, 1.09–1.43) and OS times (multivariable HR, 1.27; 95% CI, 1.10–1.46). Compared to cases with 0–2 altered genes, cases with three and four altered genes had multivariable HRs for OS of 1.28 (95% CI, 1.09–1.51) and 1.47 (95% CI, 1.22–1.78), respectively (<i>p</i>_trend &lt; 0.001). Patients with an increasing number of altered genes were more likely to have short DFS time (<i>p</i>_trend = 0.003) and to develop liver metastasis (<i>p</i>_trend = 0.006) rather than recurrence at local or other distant sites. In conclusion, loss of SMAD4 expression and an increasing number of altered genes were associated with unfavourable outcomes in pancreatic cancer patients. This study suggests that the accumulation of the four major driver alterations can confer a high metastatic potential to the liver, thereby impairing post-operative survival among patients with pancreatic cancer.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"9 5","pages":"339-353"},"PeriodicalIF":4.1,"publicationDate":"2023-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1b/22/CJP2-9-339.PMC10397380.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9957561","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}