International Journal of Cancer最新文献

{"title":"Randomized, two-arm, noncomparative phase 2 study of olaparib plus cediranib or durvalumab in HRR-mutated, platinum-resistant ovarian cancer: A substudy of KGOG 3045","authors":"Yoo-Na Kim,&nbsp;Je-Gun Joung,&nbsp;Eunhyang Park,&nbsp;Jae-Weon Kim,&nbsp;Jung Bok Lee,&nbsp;Jinyeong Lim,&nbsp;Sunghoon Kim,&nbsp;Chel Hun Choi,&nbsp;Hee Seung Kim,&nbsp;Jongsuk Chung,&nbsp;Byoung-Gie Kim,&nbsp;Jung-Yun Lee","doi":"10.1002/ijc.34696","DOIUrl":"10.1002/ijc.34696","url":null,"abstract":"<p>Choosing an optimal concomitant drug for combination with poly-ADP ribose polymerase (PARP) inhibitor based on patient-specific biomarker status may help increase to improve treatment efficacy in patients with ovarian cancer. However, the efficacy and safety of different PARP inhibitor-based combinations in patients with homologous recombination repair (HRR) mutations have not been evaluated in ovarian cancer. In this sub-study of Korean Gynecologic Oncology Group (KGOG) 3045, we compared the efficacy and safety of two olaparib-based combinations and biomarkers of patients with platinum-resistant ovarian cancer with HRR gene mutations. Patients were randomized to receive either olaparib (200 mg twice a day) + cediranib (30 mg daily) (Arm 1, n = 16) or olaparib (300 mg) + durvalumab (1,500 mg once every 4 weeks) (Arm 2, n = 14). The objective response rates for Arm 1 and Arm 2 were 50.0% and 42.9%, respectively. Most patients (83.3%) had <i>BRCA</i> mutations, which were similarly distributed between arms. Grade 3 or 4 treatment-related adverse events were observed in 37.5% and 35.7% of the patients, respectively, but all were managed properly. A high vascular endothelial growth factor signature was associated with favorable outcomes in Arm 1, whereas immune markers (PD-L1 expression [CPS ≥10], CD8, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio) were associated with favorable outcomes in Arm 2. The activation of homologous recombination pathway upon disease progression was associated with poor response to subsequent therapy. Based on comprehensive biomarker profiling, including immunohistochemistry, whole-exome and RNA sequencing and whole blood-based analyses, we identified biomarkers that could help inform which of the two combination strategies is appropriate given a patient's biomarker status. Our findings have the potential to improve treatment outcome for patients with ovarian cancer in the PARP inhibitor era.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"153 12","pages":"2032-2044"},"PeriodicalIF":6.4,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10031673","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":"Cotinine concentrations in maternal serum and amniotic fluid during pregnancy and risk of testicular germ cell cancer in the offspring: A prospective nested case-control study","authors":"Astrid L. Beck,&nbsp;Cecilie S. Uldbjerg,&nbsp;Youn-Hee Lim,&nbsp;Brent A. Coull,&nbsp;Karina M. Sørensen,&nbsp;Magdalena M. Utko,&nbsp;Bartlomiej Wilkowski,&nbsp;Panu Rantakokko,&nbsp;Marie Bengtsson,&nbsp;Christian Lindh,&nbsp;Jørgen H. Petersen,&nbsp;Niels E. Skakkebæk,&nbsp;Russ Hauser,&nbsp;Anders Juul,&nbsp;Elvira V. Bräuner","doi":"10.1002/ijc.34688","DOIUrl":"10.1002/ijc.34688","url":null,"abstract":"<p>Maternal smoking in pregnancy may increase the risk of testicular germ cell cancer (TGCC) in offspring, but current evidence remains inconclusive. We performed a nested case-control study using cotinine measurements in maternal serum and amniotic fluid as a biomarker for tobacco exposure during pregnancy. A total of 654 males with maternal serum (n = 359, n_{cases/controls} = 71/288) and/or amniotic fluid (n = 295, n_{cases/controls} = 66/229) samples were included. Data on TGCC diagnoses and relevant covariates were derived from nationwide Danish health registries. Cotinine was quantified by liquid chromatography tandem mass spectrometry. An adapted cox regression model estimated the risk of TGCC considering active and inactive tobacco use defined according to cotinine concentrations of &lt;, ≥15 ng/ml. Overall, the concentrations of cotinine were comparable in maternal serum and amniotic fluid (median_{serum/amniotic fluid}: 2.1/2.6 ng/ml). A strong statistically significant correlation was detected in 14 paired samples (Spearman <i>rho</i>: 0.85). Based on maternal serum cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC in offspring (HR 0.88, 95% CI 0.51; 1.52). Similarly, based on amniotic fluid cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC (HR 1.11, 95% CI 0.64; 1.95). However, different risks were observed for seminomas and nonseminomas in both matrices, but none were statistically significant. Our findings did not provide convincing evidence supporting that exposure to tobacco during pregnancy is associated with TGCC.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"154 1","pages":"71-80"},"PeriodicalIF":6.4,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.34688","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10031681","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":"Twenty-year outcome of prevalence, incidence, mortality and survival rate in patients with malignant bone tumors","authors":"Yao Xu,&nbsp;Fanqi Shi,&nbsp;Yanting Zhang,&nbsp;Mengfan Yin,&nbsp;Xiuxin Han,&nbsp;Jinyan Feng,&nbsp;Guowen Wang","doi":"10.1002/ijc.34694","DOIUrl":"10.1002/ijc.34694","url":null,"abstract":"<p>Malignant bone tumors are a group of rare malignant tumors and our study aimed to update the recent epidemiologic estimates based on the Surveillance, Epidemiology and End Results database. Patients diagnosed with malignant bone tumors from 2000 to 2019 were included and their characteristics were retrospectively described. The limited-duration prevalence, annual age-adjusted incidence and mortality were calculated, and the annual percentage changes were analyzed to quantify the rate change. Finally, observed survival and relative survival rate were illustrated. Subgroup analysis across tumor type, age, gender, tumor Grade, primary tumor site and stage was also performed. As for results, a total of 11 655 eligible patients with malignant bone tumor were selected. Osteosarcoma was the most common tumor type, followed by chondrosarcoma, Ewing sarcoma and chordoma. The estimated limited-duration prevalence of malignant bone tumors increased from 2000 (0.00069%) to 2018 (0.00749%). Steady age-adjusted incidence was observed in all patients during the study period while the highest rate occurred in osteosarcoma. Mortality rates differed in subgroups while elder patients (older than 64 years) presented the highest mortality rate compared to other age groups. In all bone tumors, the 10-year observed survival and relative survival rates were 58.0% and 61.9%, respectively. Chondrosarcoma patients had the best survival outcome, followed by osteosarcoma, Ewing sarcoma, chordoma and other bone tumors. In conclusion, different epidemiologic performance in incidence and mortality was observed across tumor type as well as other demographic and clinicopathological variables, which provide potential suggestion for further adjustment of medical resource.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"154 2","pages":"226-240"},"PeriodicalIF":6.4,"publicationDate":"2023-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10402507","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":"Variations in the agreement of self-reported cancer: A Danish nationwide study","authors":"Heidi Amalie Rosendahl Jensen,&nbsp;Trine Allerslev Horsbøl,&nbsp;Lau Caspar Thygesen,&nbsp;Michael Davidsen,&nbsp;Anne Illemann Christensen,&nbsp;Ola Ekholm","doi":"10.1002/ijc.34692","DOIUrl":"10.1002/ijc.34692","url":null,"abstract":"<p>Previous studies show that the agreement between self-reported and registry-documented diseases varies across diseases. Few studies have addressed these challenges across site-specific cancer diagnoses. The present study aimed to examine the sensitivity and negative predictive value (NPV) of self-reported cancer in a Danish nationwide survey among adults aged ≥16 years, using registry data as the criterion standard. Moreover, the influence of sociodemographic variables and time since diagnosis on sensitivity was explored using multiple logistic regression models. Self-reported data on cancer history of any site were derived from the Danish National Health Survey 2017 (n = 183 372). Individual-level survey data were linked to data from the Danish Cancer Registry on 10 site-specific cancer diagnoses. NPV was consistently high ≥99.5% across the included cancer diagnoses. In contrast, sensitivity varied greatly and was lowest for cancer in brain/central nervous system (CNS) among both men (25.6%) and women (23.9%) and highest for rectal cancer among men (96.9%) and for breast cancer among women (98.9%). Sensitivity was also relatively low for nonmelanoma skin cancer (41.4% among men; 44.6% among women) and urinary tract cancer (60.0% among men; 60.4% among women). When restricting diagnostic definitions for cancer in brain/CNS and urinary tract cancer to include only malignant neoplasms, sensitivity increased. For several cancer diagnoses, sensitivity decreased with increasing age and lower educational level, whereas conflicting results were observed for time from diagnosis to self-report. Future studies are encouraged to use self-reported cancer history data with caution and for example, include questions on only site-specific cancer diagnoses with high sensitivity.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"154 2","pages":"217-225"},"PeriodicalIF":6.4,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.34692","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10022130","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":"Recent trends in hereditary breast cancer incidence by race and age in KwaZulu-Natal, South Africa: An 11-year single-centre retrospective study (2011-2021)","authors":"Mpoi Makhetha,&nbsp;Namitha Chabilal,&nbsp;Colleen Aldous","doi":"10.1002/ijc.34687","DOIUrl":"10.1002/ijc.34687","url":null,"abstract":"<p>Breast cancer incidence has increased globally in the last decade, especially in low- and middle-income countries. In Sub-Saharan Africa, breast cancer trends have been described only in a few populations owing to the scarcity of population-specific data. Using data collected between 2011 and 2021 at Inkosi Albert Luthuli Central Hospital, this retrospective study describes demographic and genetic trends for hereditary breast cancer patients in the KwaZulu-Natal province, South Africa. Six hundred and forty-five patients were included, of whom 44.3% were Black, 36.8% Indian, 15.6% White and 3.2% Coloured. The number of annual new cases increased from eight in 2011 to 145 in 2021, with a notable increase among Blacks. The mean onset age was 46 years, and Black patients were diagnosed ~10 years earlier than White and Indian patients. Triple-negative breast cancers accounted for 20.3% of hereditary cases, and 51.1% of them were Black. Bilateral and recurrent breast cancers constituted 7.4%, while pathogenic sequence variants in <i>BRCA1/2</i> were reported in 10.4% of all patients, and the majority were Blacks and Indians. Overall, the KwaZulu-Natal province has seen an increase in hereditary breast cancer incidence in the past decade. Despite testing negative for pathogenic sequence variants, Black women frequently presented with breast cancers that are <i>BRCA1</i>-like, while Indians presented with extensive family history. This suggests that South African patients may require unique approaches to interventions, such as early detection and awareness programs among Blacks and increased genetic screening among Indians.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"154 1","pages":"65-70"},"PeriodicalIF":6.4,"publicationDate":"2023-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.34687","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10343663","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":"Circulating white blood cell traits and colorectal cancer risk: A Mendelian randomisation study","authors":"Andrei-Emil Constantinescu,&nbsp;Caroline J. Bull,&nbsp;Nicholas Jones,&nbsp;Ruth Mitchell,&nbsp;Kimberley Burrows,&nbsp;Niki Dimou,&nbsp;Stéphane Bézieau,&nbsp;Hermann Brenner,&nbsp;Daniel D. Buchanan,&nbsp;Mauro D'Amato,&nbsp;Mark A. Jenkins,&nbsp;Victor Moreno,&nbsp;Rish K. Pai,&nbsp;Caroline Y. Um,&nbsp;Emily White,&nbsp;Neil Murphy,&nbsp;Marc Gunter,&nbsp;Nicholas J. Timpson,&nbsp;Jeroen R. Huyghe,&nbsp;Emma E. Vincent","doi":"10.1002/ijc.34691","DOIUrl":"10.1002/ijc.34691","url":null,"abstract":"<p>Observational studies have suggested a protective role for eosinophils in colorectal cancer (CRC) development and implicated neutrophils, but the causal relationships remain unclear. Here, we aimed to estimate the causal effect of circulating white blood cell (WBC) counts (N = ~550 000) for basophils, eosinophils, monocytes, lymphocytes and neutrophils on CRC risk (N = 52 775 cases and 45 940 controls) using Mendelian randomisation (MR). For comparison, we also examined this relationship using individual-level data from UK Biobank (4043 incident CRC cases and 332 773 controls) in a longitudinal cohort analysis. The inverse-variance weighted (IVW) MR analysis suggested a protective effect of increased basophil count and eosinophil count on CRC risk [OR per 1-SD increase: 0.88, 95% CI: 0.78-0.99, <i>P</i> = .04; OR: 0.93, 95% CI: 0.88-0.98, <i>P</i> = .01]. The protective effect of eosinophils remained [OR per 1-SD increase: 0.88, 95% CI: 0.80-0.97, <i>P</i> = .01] following adjustments for all other WBC subtypes, to account for genetic correlation between the traits, using multivariable MR. A protective effect of increased lymphocyte count on CRC risk was also found [OR: 0.84, 95% CI: 0.76-0.93, <i>P</i> = 6.70e-4] following adjustment. Consistent with MR results, a protective effect for eosinophils in the cohort analysis in the fully adjusted model [RR per 1-SD increase: 0.96, 95% CI: 0.93-0.99, <i>P</i> = .02] and following adjustment for the other WBC subtypes [RR: 0.96, 95% CI: 0.93-0.99, <i>P</i> = .001] was observed. Our study implicates peripheral blood immune cells, in particular eosinophils and lymphocytes, in CRC development, highlighting a need for mechanistic studies to interrogate these relationships.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"154 1","pages":"94-103"},"PeriodicalIF":6.4,"publicationDate":"2023-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.34691","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9982041","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":"CANTO skin: Evaluation of skin toxicity risk factors in patients treated for breast cancer","authors":"Sofiane Allali,&nbsp;Matthieu Carton,&nbsp;Sibille Everhard,&nbsp;Sofia Rivera,&nbsp;Youssef Ghannam,&nbsp;Karine Peignaux,&nbsp;Phillippe Guilbert,&nbsp;Brigitte De La Lande,&nbsp;Claire Chara-Brunaud,&nbsp;Julien Blanchecotte,&nbsp;David Pasquier,&nbsp;Séverine Racadot,&nbsp;Céline Bourgier,&nbsp;Paul Cottu,&nbsp;Fabrice André,&nbsp;Youlia Kirova","doi":"10.1002/ijc.34664","DOIUrl":"10.1002/ijc.34664","url":null,"abstract":"<p>Skin reaction is a common toxicity during oncology management, especially followed during the radiotherapy. Its assessment and understanding of the factors influencing its occurrence, is a major issue in the management of patients treated for an early breast cancer (BC). We evaluated 8561 patients during their overall management for a BC. We focus on specific skin toxicities: erythema, fibrosis, telangiectasia and changes of skin colour. These toxicities were assessed at the baseline defined as 0-3-6 (M0), 12 (M12), 36 (M36) and 60 (M60) months. The prevalence of toxicities of interest varied over time, so at M0, 30.4% of patients had erythema while 17.7% of patients had fibrosis. At M60, the prevalence of erythema was 2%, while fibrosis remained stable at about 19%. After adjustments, at M0, there was a significant association between the onset of cutaneous erythema and obesity, the presence of axillary dissection, the type of surgery and the tumour phenotype RH+/HER2+. Concerning fibrosis, a significant association was found, at M12, with the age of the patient, obesity, Charlson score and type of surgery. Concerning the modification of skin colour at M12, we find a link between the age of the patient, obesity, tobacco consumption and alcohol consumption. The prevention of this toxicity is a major issue for the quality of life. Our results allow us to understand the risk of developing skin toxicity in a patient, depending on her intrinsic, tumour or therapeutic characteristics and to implement adapted means of prevention and monitoring.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"153 10","pages":"1797-1808"},"PeriodicalIF":6.4,"publicationDate":"2023-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10306340","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":"The relevance of the hematopoietic niche for therapy resistance in acute myeloid leukemia","authors":"Catana Allert,&nbsp;Carsten Müller-Tidow,&nbsp;Maximilian Felix Blank","doi":"10.1002/ijc.34684","DOIUrl":"10.1002/ijc.34684","url":null,"abstract":"<p>The expansion of acute myeloid leukemia (AML) blasts not only suppresses normal hematopoiesis, but also alters the microenvironment. The interplay of different components of the bone marrow gives rise to altered metabolic states and activates signaling pathways which lead to resistance and impede effective therapy. Therefore, the underlying processes and mechanisms represent attractive therapeutic leverage points for overcoming therapy resistance in AML. Here, we briefly discuss resistance mechanisms based on cell interactions and secreted soluble factors in the hematopoietic niche and provide an overview of niche-related therapeutic targets currently undergoing preclinical and clinical investigation which may help improve the outcome in AML therapy.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"154 2","pages":"197-209"},"PeriodicalIF":6.4,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.34684","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9974414","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":"Correction to Bilateral oophorectomy and rate of colorectal cancer: A prospective cohort study","authors":"","doi":"10.1002/ijc.34654","DOIUrl":"10.1002/ijc.34654","url":null,"abstract":"<p>Koch T, Therming Jørgensen J, Christensen J, et al. Bilateral oophorectomy and rate of colorectal cancer: A prospective cohort study. Int. J. Cancer.2022;150(1):38-46. doi:10.1002/ijc.33776</p><p>The authors would like to correct the following:</p><p><b>Method section - Colorectal cancer ascertainment</b></p><p>The incorrect sentence reads:</p><p>“Incident colorectal cancer diagnoses were identified using the International Classification of Disease (ICD) 8 and ICD 10 codes using the Danish Cancer Registry established in 1943 (until December 31, 2017)²⁴ and in the Danish National Patient Registry (January 1, 2018 to December 31, 2018)²⁵ (Supplementary Information Appendix <b>S1</b>).”</p><p>The sentence should read:</p><p>“Incident colorectal cancer diagnoses were identified using the International Classification of Disease (ICD) 7 and ICD 10 codes using the Danish Cancer Registry established in 1943 (until December 31, 2017)²⁴ and in the Danish National Patient Registry (January 1, 2018 to December 31, 2018)²⁵ (Supplementary Information Appendix <b>S1</b>).”</p><p>We apologise for the error.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"153 9","pages":"E7"},"PeriodicalIF":6.4,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.34654","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10539162","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":"Ex vivo expansion of lung cancer-derived disseminated cancer cells from lymph nodes identifies cells associated with metastatic progression","authors":"Steffi Treitschke,&nbsp;Kathrin Weidele,&nbsp;Adithi Ravikumar Varadarajan,&nbsp;Giancarlo Feliciello,&nbsp;Jens Warfsmann,&nbsp;Sybille Vorbeck,&nbsp;Bernhard Polzer,&nbsp;Catherine Botteron,&nbsp;Martin Hoffmann,&nbsp;Vadim Dechand,&nbsp;Tobias Mederer,&nbsp;Florian Weber,&nbsp;Melanie Werner-Klein,&nbsp;Tobias Robold,&nbsp;Hans-Stefan Hofmann,&nbsp;Christian Werno,&nbsp;Christoph A. Klein","doi":"10.1002/ijc.34658","DOIUrl":"10.1002/ijc.34658","url":null,"abstract":"<p>The cellular basis of the apparent aggressiveness in lung cancer is poorly understood but likely associated with functional or molecular features of disseminated cancer cells (DCCs). DCCs from epithelial cancers are mostly detected by antibodies directed against histogenetic markers such as cytokeratin or EpCAM. It has been argued that marker-negative metastatic founder cells might escape detection. We therefore used ex vivo sphere formation for functional detection of candidate metastasis founders. We generated cell suspensions from 199 LN samples of 131 lung cancer patients and placed them into non-adherent cell culture. Sphere formation was associated with detection of DCCs using EpCAM immunocytology and with significantly poorer prognosis. The prognostic impact of sphere formation was strongly associated with high numbers of EpCAM-positive DCCs and aberrant genotypes of expanded spheres. We also noted sphere formation in patients with no evidence of lymphatic spread, however such spheres showed infrequent expression of signature genes associated with spheres from EpCAM-positive samples and displayed neither typical lung cancer mutations (<i>KRAS</i>, <i>TP53</i>, <i>ERBB1</i>) nor copy number variations, but might be linked to disease progression &gt;5 years post curative surgery. We conclude that EpCAM identifies relevant disease-driving DCCs, that such cells can be expanded for model generation and that further research is needed to clarify the functional and prognostic role of rare EpCAM-negative sphere forming cells.</p>","PeriodicalId":180,"journal":{"name":"International Journal of Cancer","volume":"153 10","pages":"1854-1867"},"PeriodicalIF":6.4,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.34658","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10650287","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}