Pathobiology最新文献

{"title":"Guidelines for Handling of Cytological Specimens in Cancer Genomic Medicine.","authors":"Eiichi Morii,&nbsp;Yutaka Hatanaka,&nbsp;Noriko Motoi,&nbsp;Akihiko Kawahara,&nbsp;Shinji Hamakawa,&nbsp;Takeshi Kuwata,&nbsp;Tadasuke Nagatomo,&nbsp;Yoshinao Oda,&nbsp;Aikou Okamoto,&nbsp;Ryota Tanaka,&nbsp;Akira Iyoda,&nbsp;Maeda Ichiro,&nbsp;Yukiko Matsuo,&nbsp;Nobuyuki Nakamura,&nbsp;Tokiko Nakai,&nbsp;Mei Fukuhara,&nbsp;Kazuya Tokita,&nbsp;Tomohiko Yamaguchi,&nbsp;Masataka Takenaka,&nbsp;Ayako Kawabata,&nbsp;Kanako C Hatanaka,&nbsp;Kaho Tsubame,&nbsp;Yukitoshi Satoh","doi":"10.1159/000528346","DOIUrl":"10.1159/000528346","url":null,"abstract":"<p><p>Rapid advances are being made in cancer drug therapy. Since molecularly targeted therapy has been introduced, personalized medicine is being practiced, pathological tissue from malignant tumors obtained during routine practice is frequently used for genomic testing. Whereas cytological specimens fixed mainly in alcohol are considered to be more advantageous in terms of preservation of the nucleic acid quality and quantity. This article is aimed to share the information for the proper handling of cytological specimens in practice for genomic medicine based on the findings established in \"Guidelines for Handling of Cytological Specimens in Cancer Genomic Medicine (in Japanese)\" published by the Japanese Society of Clinical Cytology in 2021. The three-part practical guidelines are based on empirical data analyses; Part 1 describes general remarks on the use of cytological specimens in cancer genomic medicine, then Part 2 describes proper handling of cytological specimens, and Part 3 describes the empirical data related to handling of cytological specimens. The guidelines indicated proper handling of specimens in each fixation, preparation, and evaluation.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"289-311"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10674953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Value of Platelets and Coagulation Parameters in Predicting the Severity of Delta Variant SARS-CoV-2.","authors":"Yue-E Chen,&nbsp;Fu-le Ren,&nbsp;Xing Gu,&nbsp;Hong-Jun Zhang,&nbsp;Wen-Jie Li,&nbsp;Han Yang,&nbsp;Fen-Qing Shang","doi":"10.1159/000528318","DOIUrl":"https://doi.org/10.1159/000528318","url":null,"abstract":"<p><strong>Introduction: </strong>The present study aimed to analyze the clinical features and laboratory markers of patients with Delta variant SARS-CoV-2 and explore the role of platelet in predicting the severity of Delta.</p><p><strong>Methods: </strong>This retrospective, observational study was conducted on 863 patients laboratory-confirmed Delta variant SARS-CoV-2. These cases were sub-classified based on disease severity into mild (n = 304), moderate (n = 537), and severe (n = 22). A series of laboratory findings and clinical data were collected and analyzed during hospitalization.</p><p><strong>Results: </strong>Of 863 hospitalized patients with Delta, the median age was 38 years (interquartile range, 30-51 years) and 471 (54.58%) were male. The most common clinical symptoms mainly included cough, fever, pharyngalgia, expectoration, dyspnea, fatigue, and headache, and the commonest comorbidities were hypertension and diabetes. Among the hematological variables, neutrophil count, red blood cell count, and hemoglobin, were found to be statistically significant with regard to subcategories based of disease severity (p < 0.05). Among coagulation parameters, there was a statistically significant difference in D-dimer, fibrinogen, international normalized ratio, and prothrombin time (p < 0.05). Statistically significant differences were observed in platelet markers including platelet count, large platelet count, and plateletcrit (p < 0.05). Additionally, there was strong correlation between platelet and other parameters with disease severity. Logistical regression analysis and ROC curves showed that D-dimer was a single best marker of disease severity (p = 0.005, p < 0.0001); however, platelet (p = 0.009, p = 0.002) and plateletcrit (p = 0.002, p = 0.001) could also predict severe disease. Platelet was identified as an independent risk factor for severe Delta.</p><p><strong>Conclusion: </strong>Low platelet may be a marker of disease severity in Delta variant SARS-CoV-2 and may contribute to determine the severity of patients infected with Delta.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":"90 4","pages":"241-250"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9940264/pdf/pat-0001.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9959930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minichromosome Maintenance 4 Is Associated with Cancer Stemness and Poor Survival of Patients with Gastric Cancer.","authors":"Narutaka Katsuya,&nbsp;Akira Ishikawa,&nbsp;Aya Kido,&nbsp;Takafumi Fukui,&nbsp;Go Kobayashi,&nbsp;Yohei Sekino,&nbsp;Naohiro Uraoka,&nbsp;Takashi Babasaki,&nbsp;Wataru Yasui,&nbsp;Kazuhiro Sentani,&nbsp;Naohide Oue","doi":"10.1159/000525590","DOIUrl":"https://doi.org/10.1159/000525590","url":null,"abstract":"<p><strong>Introduction: </strong>Gastric cancer (GC) is a leading cause of cancer-related death worldwide. This study focused on minichromosome maintenance 4 (MCM4), a DNA helicase component that functions in DNA replication. Using spheroid colony formation, having a colony rich in cancer stem cells, this study aimed to investigate the clinicopathological importance of MCM4.</p><p><strong>Methods: </strong>We examined MCM4 expression using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) analysis in 10 and 113 GC cases, respectively. MCM4 function in GC was also investigated by RNA interference in GC cell lines.</p><p><strong>Results: </strong>In qRT-PCR and IHC analysis, high MCM4 expression was found in 60% and 83% of GC cases, respectively. MCM4-positive GC cases were significantly associated with higher T grade and tumor stage. Additionally, high MCM4 expression was significantly associated with poor prognosis and was an independent prognostic factor in multivariate analysis. MCM4 was significantly coexpressed with CD133, matrix metalloproteinase 7 (MMP7), epidermal growth factor (EGFR), and mesenchymal-epithelial transition factor (cMET). In GC cell lines, MCM4 knockdown affected cell growth and protein kinase B (Akt), extracellular signal-regulated kinase (ERK), and EGFR pathways.</p><p><strong>Conclusion: </strong>These results indicate that MCM4 expression could be a key regulator in GC progression and is pivotal in treating GC.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":"90 3","pages":"147-154"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10007487","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 of Molecular Alterations in a Swiss Cohort of 512 Colorectal Carcinoma Patients by Targeted Next-Generation Sequencing Analysis in Routine Diagnostics.","authors":"Simon Haefliger,&nbsp;Katharina Marston,&nbsp;Ilaria Alborelli,&nbsp;Edouard-Jean Stauffer,&nbsp;Mathias Gugger,&nbsp;Philip M Jermann,&nbsp;Sylvia Hoeller,&nbsp;Luigi Tornillo,&nbsp;Luigi M Terracciano,&nbsp;Michel Bihl,&nbsp;Matthias S Matter","doi":"10.1159/000526117","DOIUrl":"https://doi.org/10.1159/000526117","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal carcinoma (CRC) is among the most common carcinomas in women and men. In the advanced stage, patients are treated based on the RAS status. Recent studies indicate that in the future, in addition to KRAS and NRAS, alterations in other genes, such as PIK3CA or TP53, will be considered for therapy. Therefore, it is important to know the mutational landscape of routinely diagnosed CRC.</p><p><strong>Method: </strong>We report the molecular profile of 512 Swiss CRC patients analyzed by targeted next-generation sequencing as part of routine diagnostics at our institute.</p><p><strong>Results: </strong>Pathogenic and likely pathogenic variants were found in 462 (90%) CRC patients. Variants were detected in TP53 (54.3%), KRAS (48.2%), PIK3CA (15.6%), BRAF (13.5%), SMAD4 (10.5%), FBXW7 (7.8%), NRAS (3.5%), PTEN (2.7%), ERBB2 (1.6%), AKT1 (1.5%), and CTNNB1 (0.9%). The remaining pathogenic alterations were found in the genes ATM(n= 1), MAP2K1(n= 1), and IDH2(n= 1).</p><p><strong>Discussion/conclusions: </strong>Our analysis revealed the prevalence of potential predictive markers in a large cohort of CRC patients obtained during routine diagnostic analysis. Furthermore, our study is the first of this size to uncover the molecular landscape of CRC in Switzerland.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":"90 3","pages":"166-175"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10273900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9644486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Prognostic Impact of the Warburg Effect in Esophageal Carcinoma: Monocarboxylate Transporters as Candidates for Therapeutic Targeting.","authors":"Julieta Afonso,&nbsp;Andreia Barbosa,&nbsp;Paula Roberta Aguiar Pastrez,&nbsp;Murilo Bonatelli,&nbsp;Ricardo Filipe Alves da Costa,&nbsp;Céline Pinheiro,&nbsp;Adhemar Longatto-Filho,&nbsp;Fátima Baltazar","doi":"10.1159/000528562","DOIUrl":"https://doi.org/10.1159/000528562","url":null,"abstract":"<p><strong>Introduction: </strong>Esophageal cancer (EC) seems to display increased glycolytic activity, but clinical studies on the expression/prognostic significance of glycometabolism-related proteins, as well as functional assays, are missing.</p><p><strong>Methods: </strong>Expression of 10 glycolytic biomarkers was evaluated by immunohistochemistry in tissue sections from 95 patients. Two esophageal squamous cell carcinoma (ESCC) cell lines were used to assess the effect of monocarboxylate transporter (MCT) downregulation on cell viability and extracellular lactate/glucose accumulation.</p><p><strong>Results: </strong>Expression of MCT1, MCT4, CD147, and GLUT1 was significantly associated with an ESCC histopathology, while a poor clinicopathological profile was seen in GLUT1- and LDHA-positive EC cases. In the ESCC group, MCT1 immunoreactivity is associated with high TNM stage and metastasis. The 3-year overall survival (OS) rate was significantly influenced by MCT4 and CAIX positivity and HKII negativity. Those biomarkers were considered independent prognostic factors of OS in multivariate analysis. Dual inhibition of MCT1/4 expression decreased cell viability and extracellular lactate accumulation in ESCC cells.</p><p><strong>Conclusion: </strong>Elevated glycolytic rates correlate with a poor clinicopathological profile in EC patients. MCT4 and CAIX positivity independently predict a worse prognosis. Due to the lack of information on treatment modalities, we could not further infer the role of these biomarkers in predicting response to therapy, which needs to be assessed in future studies. In addition, MCT1/4 targeting should be performed both \"in vitro\" and \"in vivo\" to further explore its impact on tumor growth and response to classical therapies. HKII expression and function, particularly in the tumor stroma, should be investigated.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":"90 4","pages":"251-269"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9959928","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":"Distribution and Clinical Significance of HPV16 Variants in Head and Neck Squamous Cell Carcinomas: Data from a Portuguese Cohort and Systematic Review.","authors":"Daniela Cochicho,&nbsp;Alexandra Nunes,&nbsp;Daniel Sobral,&nbsp;João P Gomes,&nbsp;Susana Esteves,&nbsp;Joana Mendonça,&nbsp;Luis Vieira,&nbsp;Luís Martins,&nbsp;Mario Cunha,&nbsp;Pedro Montalvão,&nbsp;Miguel Magalhães,&nbsp;Rui M Gil da Costa,&nbsp;Ana Félix","doi":"10.1159/000529723","DOIUrl":"10.1159/000529723","url":null,"abstract":"<p><strong>Introduction: </strong>Genomic variants of the human papillomavirus type 16 (HPV16) are thought to play differential roles in the susceptibility to head and neck squamous cell carcinomas (HNSCC) and its biological behaviour. This study aimed to establish the prevalence of HPV16 variants in an HNSCC cohort and associate them with clinical pathological characteristics and patient survival.</p><p><strong>Methods: </strong>We retrieved samples and clinical data from 68 HNSCC patients. DNA samples were available from tumour biopsy at the time of the primary diagnosis. Targeted next-generation sequencing was used to obtain whole-genome sequences, and variants were established based on phylogenetic classification.</p><p><strong>Results: </strong>74% of samples clustered in lineage A, 5.7% in lineage B, 2.9% in lineage C, and 17.1% in lineage D. Comparative genome analysis revealed 243 single nucleotide variations. Of these, one hundred were previously reported, according to our systematic review. No significant associations with clinical pathological variables or patient survival were observed. The E6 amino acid variations E31G, L83V, and D25E and E7 N29S, associated with cervical cancer, were not observed, except for N29S in a single patient.</p><p><strong>Conclusion: </strong>These results provide a comprehensive genomic map of HPV16 in HSNCC, highlighting tissue-specific characteristics which will help design tailored therapies for cancer patients.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"333-343"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9277216","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":"DAXX, ATRX, and MSI in PanNET and Their Metastases: Correlation with Histopathological Data and Prognosis.","authors":"Doreen Maria Gisder,&nbsp;Oliver Overheu,&nbsp;Julia Keller,&nbsp;Stefanie Nöpel-Dünnebacke,&nbsp;Waldemar Uhl,&nbsp;Anke Reinacher-Schick,&nbsp;Andrea Tannapfel,&nbsp;Iris Tischoff","doi":"10.1159/000524920","DOIUrl":"https://doi.org/10.1159/000524920","url":null,"abstract":"<p><strong>Introduction: </strong>Studies on pancreatic neuroendocrine tumors (PanNETs) regarding loss of ATRX, DAXX, or frequency of microsatellite instability (MSI) show inconclusive results. So far, data on corresponding metastaseshave not been published.</p><p><strong>Methods: </strong>We performed immunohistochemistry (IHC) of ATRX, DAXX, MSH2, MSH6, MLH1, and PMS2 on 74 PanNETs and 19 metastases. ATRX- and DAXX-negative PanNETs were further sequenced for mutations. We used polymerase chain reaction for MSI on cases with IHC loss of MSH2, MSH6, MLH1, and PMS2.</p><p><strong>Results: </strong>Immunohistochemical loss of DAXX and ATRX was observed in 8/74 (11%) and 6/74 (8%) PanNETs. Loss of DAXX immunoreactivity was statistically associated with higher tumor grade and showed a tendency toward a decreased overall survival. Sequencing of DAXX- (7/11 [64%]) and ATRX-negative (5/11 [45%]) PanNETs revealed a mutation in 6/7 (86%) and 2/5 (40%). The specificity of immunohistochemical loss of DAXX and ATRX for mutation was 80% and 67%, respectively. The expression status of DAXX compared to primary tumor differs in 2/12 (17%) lymph node metastases. We further identified 3/74 (4%) tumors as MSI, associated with a poor prognosis.</p><p><strong>Discussion/conclusion: </strong>Our study supports the hypothesis that a loss of DAXX immunoreactivity can identify a more aggressive subtype of PanNET with high confidence, while ATRX loss is a weaker indicator. Our results also strengthen the role of DAXX immunolabeling as a prognostic marker. We could show that ATRX might be less suitable as a surrogate for sequencing. Our results indicate that IHC of DAXX and ATRX may identify PanNET subtypes as targets for more aggressive therapy.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":"90 2","pages":"71-80"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9300383","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":"ANXA10 Expression Is Inversely Associated with Tumor Stage, Grade, and TP53 Expression in Upper and Lower Urothelial Carcinoma.","authors":"Go Kobayashi,&nbsp;Tetsutaro Hayashi,&nbsp;Kazuhiro Sentani,&nbsp;Kenichiro Ikeda,&nbsp;Takashi Babasaki,&nbsp;Yoshinori Shigematsu,&nbsp;Yohei Sekino,&nbsp;Naohiro Uraoka,&nbsp;Jun Teishima,&nbsp;Akio Matsubara,&nbsp;Nobuyuki Hinata,&nbsp;Naohide Oue","doi":"10.1159/000524989","DOIUrl":"https://doi.org/10.1159/000524989","url":null,"abstract":"<p><strong>Introduction: </strong>Urothelial carcinoma (UC) is a common type of malignant disease, but little is known about the diagnostic and prognostic markers of upper urinary tract urothelial cancer (UTUC) because of its rarity. To clarify the significance of ANXA10 in UTUC, we studied ANXA10 expression with immunohistochemistry (IHC).</p><p><strong>Methods: </strong>The expression of ANXA10 was analyzed in the upper and lower urinary tract of UC by IHC in combination with The Cancer Genome Atlas (TCGA) data analysis. The association between ANXA10 expression and representative cancer-related molecules was also evaluated.</p><p><strong>Results: </strong>ANXA10 expression was weak in normal upper tract urothelium but was positive in 39/117 (33%) UTUCs. ANXA10 was more frequently positive in tumors with pure UC (36%, p < 0.05), papillary morphology (50%, p < 0.01), low grade (G1/2: 57%, p < 0.01), and pTa/is/1 stage (55%, p < 0.01) than in those with histological variants (0%), nodular morphology (9%), G3 (16%), and pT2/3/4 (13%), respectively. ANXA10-positive patients showed better cancer-specific survival and progression-free survival than ANXA10-negative patients (p < 0.05). IHC showed that ANXA10 positivity was detected more in cases with the low expression of TP53 (p < 0.01) and Ki-67 labeling index <20% (p < 0.01). In TCGA dataset of muscle-invasive bladder cancer, higher ANXA10 expression correlated with papillary morphology, lower grade/stage, luminal papillary subtype, wild-type TP53, and FGFR3 gene mutation.</p><p><strong>Conclusion: </strong>We revealed that ANXA10 expression was increased during carcinogenesis and was observed more frequently in papillary UC of lower grade and stage. However, its expression decreased as cancer progressed. Therefore, the ANXA10 expression in UTUC might be clinically useful for decision-making.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":"90 2","pages":"94-103"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9361502","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":"Impact of Region-of-Interest Size on Immune Profiling Using Multiplex Immunofluorescence Tyramide Signal Amplification for Paraffin-Embedded Tumor Tissues.","authors":"Baohua Sun, Caddie Laberiano-Fernández, Ruth Salazar-Alejo, Jiexin Zhang, Jose Luis Solorzano Rendon, Jack Lee, Luisa Maren Solis Soto, Ignacio Ivan Wistuba, Edwin Roger Parra","doi":"10.1159/000523751","DOIUrl":"10.1159/000523751","url":null,"abstract":"<p><strong>Introduction: </strong>Representative regions of interest (ROIs) analysis from the whole slide images (WSI) are currently being used to study immune markers by multiplex immunofluorescence (mIF) and single immunohistochemistry (IHC). However, the amount of area needed to be analyzed to be representative of the entire tumor in a WSI has not been defined.</p><p><strong>Methods: </strong>We labeled tumor-associated immune cells by mIF and single IHC in separate cohorts of non-small cell lung cancer (NSCLC) samples and we analyzed them as whole tumor area as well as using different number of ROIs to know how much area will be need to represent the entire tumor area.</p><p><strong>Results: </strong>For mIF using the InForm software and ROI of 0.33 mm2 each, we observed that the cell density data from five randomly selected ROIs is enough to achieve, in 90% of our samples, more than 0.9 of Spearman correlation coefficient and for single IHC using ScanScope tool box from Aperio and ROIs of 1 mm2 each, we found that the correlation value of more than 0.9 was achieved using 5 ROIs in a similar cohort. Additionally, we also observed that each cell phenotype in mIF influence differently the correlation between the areas analyzed by the ROIs and the WSI. Tumor tissue with high intratumor epithelial and immune cells phenotype, quality, and spatial distribution heterogeneity need more area analyzed to represent better the whole tumor area.</p><p><strong>Conclusion: </strong>We found that at minimum 1.65 mm2 area is enough to represent the entire tumor areas in most of our NSCLC samples using mIF.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":"90 1","pages":"1-12"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10623106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the Immune Microenvironment in Inflammatory Breast Cancer Using Multiplex Immunofluorescence.","authors":"Nahla M Badr, Jack L McMurray, Irini Danial, Steven Hayward, Nancy Y Asaad, Moshira M Abd El-Wahed, Asmaa G Abdou, Marwa M Serag El-Dien, Nisha Sharma, Yoshiya Horimoto, Tapan Sircar, Raghavan Vidya, Fiona Hoar, Daniel Rea, J Louise Jones, Andrea Stevens, David Spooner, Reena Merard, Paul Lewis, Kelly John Hunter, Fedor Berditchevski, Abeer M Shaaban","doi":"10.1159/000524549","DOIUrl":"10.1159/000524549","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with a poorly characterized immune microenvironment.</p><p><strong>Methods: </strong>We used a five-colour multiplex immunofluorescence panel, including CD68, CD4, CD8, CD20, and FOXP3 for immune microenvironment profiling in 93 treatment-naïve IBC samples.</p><p><strong>Results: </strong>Lower grade tumours were characterized by decreased CD4+ cells but increased accumulation of FOXP3+ cells. Increased CD20+ cells correlated with better response to neoadjuvant chemotherapy and increased CD4+ cells infiltration correlated with better overall survival. Pairwise analysis revealed that both ER+ and triple-negative breast cancer were characterized by co-infiltration of CD20 + cells with CD68+ and CD4+ cells, whereas co-infiltration of CD8+ and CD68+ cells was only observed in HER2+ IBC. Co-infiltration of CD20+, CD8+, CD4+, and FOXP3+ cells, and co-existence of CD68+ with FOXP3+ cells correlated with better therapeutic responses, while resistant tumours were characterized by co-accumulation of CD4+, CD8+, FOXP3+, and CD68+ cells and co-expression of CD68+ and CD20+ cells. In a Cox regression model, response to therapy was the most significant factor associated with improved patient survival.</p><p><strong>Conclusion: </strong>Those results reveal a complex unique pattern of distribution of immune cell subtypes in IBC and provide an important basis for detailed characterization of molecular pathways that govern the formation of IBC immune landscape and potential for immunotherapy.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":"90 1","pages":"31-43"},"PeriodicalIF":5.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10668709","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}