Guomin Gu, Chunling Liu, Yan Yang, Yan Zhao, Xiaodan Zhu, Gang Sun
{"title":"The impact of KRAS mutations on the tumour microenvironment and treatment response in non-small cell lung cancer.","authors":"Guomin Gu, Chunling Liu, Yan Yang, Yan Zhao, Xiaodan Zhu, Gang Sun","doi":"10.5114/pjp.2024.146544","DOIUrl":"10.5114/pjp.2024.146544","url":null,"abstract":"<p><p>Mutations in the KRAS gene in non-small cell lung cancer (NSCLC) are common drivers. Gene expression and mutation data of NSCLC were collected from the TCGA dataset. DEGs between KRAS mutations and wild type were identified, and enrichment analysis was performed. The differences in immune cell infiltration between the 2 groups were evaluated using ssGSEA, and TIDE scoring, immune checkpoint therapy sensitivity, and drug treatment sensitivity analysis were performed. The expression of PD-L1 and CTLA-4 in tumour tissues was detected by western blot. CD8+PD-1 and CD8+CTLA-4 cells were detected by flow cytometry. The frequencies of KRAS-G12C, KRAS-G12V, and KRAS-G12D mutations were the highest. A total of 1323 DEGs were predominantly enriched in the PI3K-Akt signalling pathway, cell adhesion molecules, and metabolism of xenobiotics by cytochrome P450. Additionally, most immune cell infiltration levels in KRAS mutations were lower than in KRAS wild type. Sensitivity to immune checkpoint inhibitors and drug treatments increased in KRAS mutations. Western blot revealed significantly higher expressions of PD-L1 and CTLA-4 in KRAS mutations compared to KRAS wild type. The infiltration of CD8+PD-1+ T cells and CD8+CTLA-4+ T cells was higher in KRAS mutations than in KRAS wild type. KRAS-G12C, KRAS-G12V, and KRAS-G12D mutations may enhance NSCLC drug resistance through immunosuppression.</p>","PeriodicalId":49692,"journal":{"name":"Polish Journal of Pathology","volume":"75 4","pages":"353-361"},"PeriodicalIF":0.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Classical autoimmune hepatitis and the IgG4-associated autoimmune hepatitis in paediatric patients.","authors":"Dominika Kaps-Kopiec, Małgorzata Woźniak, Dorota Jarzębicka, Renata Grzywa-Czuba, Joanna Pawłowska, Piotr Czubkowski, Joanna Cielecka-Kuszyk","doi":"10.5114/pjp.2024.141231","DOIUrl":"https://doi.org/10.5114/pjp.2024.141231","url":null,"abstract":"<p><p>The IgG4-associated autoimmune hepatitis (IgG4-AIH) is a newly proposed disease entity characterised by the accumulation of the IgG4-expressing plasma cells in the liver. Its pathophysiology and clinical significance remain unclear and have poor evidence in the paediatric population. Thus, our study aims at comparing the group of paediatric patients with classical AIH and the IgG4-AIH. We carried out a retrospective analysis of 23 children (median age 8.5 years) diagnosed with AIH, who were compared according to the presence of IgG4-positive plasma cells in the liver biopsy. IgG4-AIH was defined if 10 or more IgG4 positive plasma cells/high-power field were found in the biopsy. The presence of the IgG4 component seems to be clinically insignificant. That is why, the conventional immunosuppressive protocol should be considered the standard treatment in the case of the IgG4-associated AIH.</p>","PeriodicalId":49692,"journal":{"name":"Polish Journal of Pathology","volume":"75 2","pages":"153-156"},"PeriodicalIF":0.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mariya Stoilova, Maria Koleva, Marin Baltov, Albena Fakirova, Dorian Dikov
{"title":"Quiz CORRECT ANSWER TO THE QUIZ. CHECK YOUR DIAGNOSIS Prostatic paraganglia-hyperplasia - a histological mimic of intraprostatic adipose tissue.","authors":"Mariya Stoilova, Maria Koleva, Marin Baltov, Albena Fakirova, Dorian Dikov","doi":"10.5114/pjp.2024.141368","DOIUrl":"10.5114/pjp.2024.141368","url":null,"abstract":"<p><p>Prostatic paraganglia (PP) can simulate adenocarcinoma's fused gland pattern, and a differential diagnostic panel is developed. Their differential diagnosis with benign prostatic lesions has been largely unreported. Intraprostatic adipose tissue (IPAT) is seen extremely rarely in prostatic specimens, but it must be known, to avoid false positive results for extraprostatic fat carcinomatous invasion in needle biopsy specimens. We present one case from 100 randomly selected radical prostatectomy specimens in which our diagnosis evolved from IPAT to PP-hyperplasia, after additional immunohistochemical investigations. The presence of PP-hyperplasia, with both parenchymal and neurovascular bundle location, and its differential diagnosis with IPAT has not been previously reported.</p>","PeriodicalId":49692,"journal":{"name":"Polish Journal of Pathology","volume":"75 3","pages":"256-258"},"PeriodicalIF":0.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prevalence, distribution, and prognostic significance of morphological variants of neuroendocrine tumors of the gastrointestinal tract - a multicenter study.","authors":"Ebru Akay, Melike Ordu, Ganime Çoban, Seher Darakcı, Nahit Topaloğlu, Filiz Meral Taştekin, Büşra Ekinci, Nurhan Şahin, Zuhal Gucin, Hatice Karaman","doi":"10.5114/pjp.2024.141014","DOIUrl":"10.5114/pjp.2024.141014","url":null,"abstract":"<p><p>The incidence and prevalence of neuroendocrine neoplasms (NENs) in many organs are increasing. Although such NENs have similar grades, they may exhibit quite different behaviors. In this multicenter study, we aimed to investigate the prevalence and distribution of different morphological NEN variants in the non-pancreatic gastrointestinal (GI) tract and determine whether they can guide prognosis prediction. Two hundred and fifty-six patients diagnosed with NENs originating from the GI tract from 7 different centers were included in the study. In 89 (36.6%) cases, different morphological variants were detected. When the variants were grouped according to their aggressiveness as described in the literature, a statistically significant relationship between aggressiveness and the variables organ and age was found ( p < 0.05). The oncocytic variant was found to metastasize more than the other aggressive types (42.9%). The paraganglioma-like variant was found to have a smaller size, lower proliferation index, and a more benign clinical course. This study demonstrated that well-differentiated GI neuroendocrine tumors (GI-NETs) have considerable morphological diversity. Generally, case reports of rare morphological variants of GI-NETs are available in the literature. We believe that our study contributes to a better understanding of the prevalence, localization, and significance of morphological variations in GI-NETs.</p>","PeriodicalId":49692,"journal":{"name":"Polish Journal of Pathology","volume":"75 2","pages":"126-137"},"PeriodicalIF":0.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CircRNA TUBA1C promotes proliferation and glucose metabolism, and blocks apoptosis of osteosarcoma cells through sponging miR-143-3p.","authors":"Yi-Bing Liu, Wen-Hao Dai, Jun-Jie Chang, Kang Wei","doi":"10.5114/pjp.2024.143231","DOIUrl":"https://doi.org/10.5114/pjp.2024.143231","url":null,"abstract":"<p><p>Osteosarcoma (OS) is a malignant bone tumour that commonly occurs in paediatric and adolescent patients. Currently, effective therapy for OS remains elusive due to poor patient survival rates. In this study, we observed significantly elevated expressions of circTUBA1C in OS tumours and cells. Silencing circTUBA1C effectively suppressed proliferation and glucose metabolism, and promoted apoptosis of OS cells. Furthermore, we discovered that miR-143-3p played a reverse role to circTUBA1C in OS cells. Bioinformatics analysis, RNA pull-down assay, and luciferase assay demonstrated that circTUBA1C acted as a sponge for miR-143-3p, blocking its expression in OS cells. Finally, rescue experiments showed that inhibition of miR-143-3p in circTUBA1C-silenced OS cells significantly overrode the low-circTUBA1C-mediated miR-143-3p upregulation and OS cell progression in vitro and in vivo . Our results demonstrate the critical roles and molecular targets of circTUBA1C in modulating OS progression, suggesting that circTUBA1C inhibition could serve as a new therapeutic strategy for treating OS.</p>","PeriodicalId":49692,"journal":{"name":"Polish Journal of Pathology","volume":"75 3","pages":"215-227"},"PeriodicalIF":0.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paulina Poter, Sylwia Jankowska-Szabłowska, Tomasz Kolenda, Ewa Dobak, Elżbieta Urasińska, Katarzyna Karpińska-Łukaszewicz
{"title":"Association of PD-1 and PD-L1 protein expression with selected clinical and morphological parameters in colorectal cancers.","authors":"Paulina Poter, Sylwia Jankowska-Szabłowska, Tomasz Kolenda, Ewa Dobak, Elżbieta Urasińska, Katarzyna Karpińska-Łukaszewicz","doi":"10.5114/pjp.2024.139935","DOIUrl":"https://doi.org/10.5114/pjp.2024.139935","url":null,"abstract":"<p><p>Colorectal cancer is the third most common cancer worldwide and the second cause of death from malignant tumors. Colorectal cancers are treated with surgery, chemotherapy, gene therapy and immunotherapy. PD-1 and PD-L1 proteins have recently been considered as potential targets of anticancer therapy in colorectal cancer. The aim of this study was to evaluate the association of immunohistochemical expression of PD-1 and PD-L1 proteins in colorectal cancer patients with selected clinical and morphological parameters and their survival. Ninety-eight cases of colorectal cancer were studied. Immunohistochemistry was used to evaluate the expression of PD-1 and PD-L1 proteins. Correlations were found between the expression of PD-L1 protein in lymphocytes and lack of lymph node metastases and a lower clinical stage. There was also a correlation between PD-L1 protein expression in cancer cells and a higher grade of histological malignancy.</p>","PeriodicalId":49692,"journal":{"name":"Polish Journal of Pathology","volume":"75 2","pages":"105-114"},"PeriodicalIF":0.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Leukaemia-related protein 16 is highly expressed in oestrogen-dependent endometrial carcinoma and potentially promotes Ishikawa human endometrial cancer cells growth - a histopathological study.","authors":"Qing Zhu, Li-Gao Wu, Zhen-Zhong Feng, Qiang Wu","doi":"10.5114/pjp.2024.139609","DOIUrl":"https://doi.org/10.5114/pjp.2024.139609","url":null,"abstract":"<p><p>Leukaemia-related protein 16 (LRP16) has been found to be highly expressed in various tumours and to be related to poor prognosis. However, the role of LRP16 in endometrial carcinoma remains to be explored. We aimed to investigate the prognosis and role of LRP16 in endometrial carcinoma. Overall, 160 endometrial carcinoma (EC) tissues and 60 benign samples were collected. The expression of LRP16 protein in EC tissues was significantly increased compared with that in normal endometrial tissues, and high LRP16 expression was related to poor patient prognosis. Reduced LRP16 expression markedly inhibited cancer cell growth. The proliferation rates in the prophylactic bilateral salpingectomy (PBS) group and the shNon group were 0.727 ±0.015 and 0.743 ±0.009, respectively, while the proliferation rate in the shLRP16 group was only 0.373 ±0.012. The migration experiment showed that the number of cells passing through the basement membrane in the shLRP16 group was 34.2 ±5.1, which was significantly different to the shNon (161.6 ±7.8) and PBS groups (138.0 ±7.2). The results of the invasion experiment showed that the number of cells was 39.2 ±6.2 in the shLRP16 group, 146.7 ±8.2 in the shNon group, and 141.2 ±8.1 in the PBS group ( p < 0.05). Leukaemia-related protein 16 is highly expressed in oestrogen-dependent EC and may promote cancer cell growth.</p>","PeriodicalId":49692,"journal":{"name":"Polish Journal of Pathology","volume":"75 2","pages":"97-104"},"PeriodicalIF":0.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinicopathological characteristics and BRCA1/BRCA2 pathogenic variants of patients with breast cancer.","authors":"Nazan Eras, Ferah Tuncel, Zuhal Altıntas, Sema Erden","doi":"10.5114/pjp.2024.135703","DOIUrl":"10.5114/pjp.2024.135703","url":null,"abstract":"<p><p>Although BRCA genes are well-known breast cancer genes, the clinicopathological features of breast cancer patients carrying BRCA1/2 pathogenic variants have not been adequately defined. The goals of this study were to determine the distribution of BRCA1/2 variants in the Turkish population and its correlation with clinicopathological features. Clinical data of 151 women who underwent BRCA1/2 gene testing at Mersin University Medical Faculty Hospital between 2016 and 2019 were retrospectively analyzed. BRCA1/2 variants were detected as pathogenic (n = 11), variants of uncertain significance (n = 5), likely benign (n = 3), and benign (n = 81) in breast cancer cases. The BRCA1/2 pathogenic variant carriers had a higher histological grade, rate of triple- negative type, Ki-67 proliferation index, and rate of no special type carcinoma than the group without mutation (p = 0.03, 0.01, 0.04, and 0.02 respectively). We analyzed the distribution of variants we detected in women living in our region and found that pathogenic variants in patients with breast cancer were associated with high histological grade, triple-negative type, high Ki-67 proliferation index, and histological type. Studies in diverse populations are needed to establish a clinicopathological relationship with variants more easily.</p>","PeriodicalId":49692,"journal":{"name":"Polish Journal of Pathology","volume":"75 1","pages":"1-7"},"PeriodicalIF":0.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A study on expression of programmed death ligand-1 in small cell lung carcinoma and correlation with clinicopathological parameters.","authors":"Sudha Sudha, Saumya Shukla, Nuzhat Husain, Hemant Kumar, Rahul Kumar Pandey, Surya Kant","doi":"10.5114/pjp.2024.136281","DOIUrl":"10.5114/pjp.2024.136281","url":null,"abstract":"<p><p>Small cell lung carcinoma (SCLC) is characterized by rapid growth and an aggressive clinical course. Standard therapy regimes have limited effects on disease course; therefore the prognosis of SCLC is poor. In the current study, the frequency of programmed death ligand 1 (PD-L1) expression in SCLC and its correlation with clinico-pathological features were evaluated. The study included 100 cases of SCLC wherein testing for PD-L1 was done with the SP263 clone on the Ventana benchmark XT system. Cases with > 1% PD-L1 expression in tumour cells or immune cells were categorized as positive. PD-L1 expression was identified in 14% of cases using the cut-off of ≥ 1%. The tumour proportion score was 10% and the immune proportion score was 9.78% using a cut-off of ≥ 1%. PD-L1 positive expression was more frequent in the male population with age > 40 years. All the patients with positive PD-L1 expression were smokers. In the PD-L1 positive group, presence of necrosis was identified in 71.4% of cases and when compared with the PD-L1 negative subgroup this finding was statistically significant (p = 0.010). Personalized targeted therapy for cases of SCLC is still under evaluation. The use of immunotherapeutic targets, such as PD-L1, may help to define a new treatment strategy for SCLC. Development of new treatment strategies may improve prognosis and survival.</p>","PeriodicalId":49692,"journal":{"name":"Polish Journal of Pathology","volume":"75 1","pages":"25-35"},"PeriodicalIF":0.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epithelial mesenchymal transition and cancer stem cell markers in oral epithelial dysplasia and oral squamous cell carcinoma.","authors":"Burcu Tokozlu, Özlem Özer Yücel, Sibel E Gültekin, Leyla Arslan Bozdağ","doi":"10.5114/pjp.2024.145818","DOIUrl":"10.5114/pjp.2024.145818","url":null,"abstract":"<p><p>The role of cancer stem cells (CSC) in oral cancer is widely accepted. Yet, the existence of CSC in dysplastic tissue and the molecular pathways of progression from dysplasia to malignancy remain to be explored. Our retrospective study aimed to analyze the presence of CSC in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC) concerning two epithelial-mesenchymal transition markers: Snail and E-cadherin. Formalin-fixed, paraffin-embedded tissue samples of oral epithelial dysplasia (OED), OSCC, and oral epithelial hyperplasia (OEH) were used. Immunohistochemistry and quantitative RT-qPCR detected the expression of Snail and CD133, whereas CD44 and E-cadherin were evaluated solely immunohistochemically. OSCC cases showed significantly higher CD133 immunoreactivity and inflammation scores and significantly decreased E-cadherin expression compared to OED and OEH groups. Snail mRNA up-regulation was seen in 100% of the OSCC cases followed by 85% for OED cases and 82.5% OEH cases among those that displayed positive mRNA expression by RT-qPCR. The Snail upregulation in all OSCC cases proves that Snail plays a significant role in oral cancer. Our results also suggest that CD133 and E-cadherin may be potential diagnostic markers in oral cancer progression.</p>","PeriodicalId":49692,"journal":{"name":"Polish Journal of Pathology","volume":"75 4","pages":"305-314"},"PeriodicalIF":0.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}