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| 22. |
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| 23. |
- Isaksson, Sofi, et al.
(författare)
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Pre-operative plasma cell-free circulating tumor DNA and serum protein tumor markers as predictors of lung adenocarcinoma recurrence
- 2019
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Ingår i: Acta Oncologica. - 0284-186X. ; 58:8, s. 1079-1086
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lung cancer patients have a risk of recurrence even after curatively intended surgery. Cell-free circulating tumor DNA (ctDNA) and circulating tumor marker measurements are easily accessible through peripheral blood and could potentially identify patients with worse prognosis. The aim of this study was to examine ctDNA in pre-operative plasma and the role of tumor markers in pre-operative serum for their predictive potential on risk of tumor recurrence. Methods: Mutation analysis by 26-gene targeted sequencing was performed on 157 lung adenocarcinomas (ACs) from patients surgically treated at the Lund University Hospital 2005–2014. Of these, 58 tumors from patients in stages I–IIIA (34 stage I, 14 stage II and 10 stage III) with mutation(s) in EGFR, BRAF or KRAS were included. ctDNA from corresponding plasma (median 1.5 ml, range 1–1.6) was analyzed for one tumor-specific mutation in either of these three oncogenes using ultrasensitive IBSAFE droplet digital PCR (ddPCR). The tumor markers cancer antigen 125 (CA 125) and carbohydrate antigen 19-9 (CA 19-9) were analyzed in corresponding serum with electrochemiluminiscence immunoassay. Results: 6/7 patients with ctDNA and 19/51 without detected ctDNA were diagnosed with recurrence (log-rank test p =.001). 8/10 patients with positive serum tumor markers and 17/47 without tumor markers were diagnosed with recurrence (log-rank test, p =.0002). Fifteen patients had positive ctDNA and/or tumor markers, 12 of these had recurrence (log-rank test, p <.0001). Conclusion: A combination of tumor markers and ctDNA single mutation detection in low-volume pre-operative blood samples is a promising prognostic test. Prediction of recurrent disease in surgically treated early stage lung cancer can likely be further improved by using larger volumes of blood.
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| 24. |
- Malmros, Karina, et al.
(författare)
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Diagnostic gastrointestinal markers in primary lung cancer and pulmonary metastases
- 2024
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Ingår i: Virchows Archiv. - 0945-6317. ; 485, s. 347-357
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Tidskriftsartikel (refereegranskat)abstract
- Histopathological diagnosis of pulmonary tumors is essential for treatment decisions. The distinction between primary lung adenocarcinoma and pulmonary metastasis from the gastrointestinal (GI) tract may be difficult. Therefore, we compared the diagnostic value of several immunohistochemical markers in pulmonary tumors. Tissue microarrays from 629 resected primary lung cancers and 422 resected pulmonary epithelial metastases from various sites (whereof 275 colorectal cancer) were investigated for the immunohistochemical expression of CDH17, GPA33, MUC2, MUC6, SATB2, and SMAD4, for comparison with CDX2, CK20, CK7, and TTF-1. The most sensitive markers for GI origin were GPA33 (positive in 98%, 60%, and 100% of pulmonary metastases from colorectal cancer, pancreatic cancer, and other GI adenocarcinomas, respectively), CDX2 (99/40/100%), and CDH17 (99/0/100%). In comparison, SATB2 and CK20 showed higher specificity, with expression in 5% and 10% of mucinous primary lung adenocarcinomas and both in 0% of TTF-1-negative non-mucinous primary lung adenocarcinomas (25–50% and 5–16%, respectively, for GPA33/CDX2/CDH17). MUC2 was negative in all primary lung cancers, but positive only in less than half of pulmonary metastases from mucinous adenocarcinomas from other organs. Combining six GI markers did not perfectly separate primary lung cancers from pulmonary metastases including subgroups such as mucinous adenocarcinomas or CK7-positive GI tract metastases. This comprehensive comparison suggests that CDH17, GPA33, and SATB2 may be used as equivalent alternatives to CDX2 and CK20. However, no single or combination of markers can categorically distinguish primary lung cancers from metastatic GI tract cancer.
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| 25. |
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| 26. |
- Planck, M, et al.
(författare)
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Increased cancer risk in offspring of women with colorectal carcinoma : a Swedish register-based cohort study
- 2000
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Ingår i: Cancer. - 0008-543X. ; 89:4, s. 9-741
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Colorectal carcinoma is one of the most common malignancies in the Western population, and a considerable proportion of colorectal carcinomas are estimated to have a familial background.METHODS: Individuals whose mothers were diagnosed with colon carcinoma or rectal carcinoma from 1958 to 1993, a total of 1. 48 million person-years, constituted the cohort of this Swedish population-based register study. The children were born during the period 1941-1993, and the cancer incidence was observed during the period 1961-1993, with the expected national Swedish incidence used as a reference.RESULTS: A significantly increased risk of colon carcinoma, rectal carcinoma, and non-Hodgkin lymphoma was observed in the cohort. The cancer risk was more pronounced in children whose mothers were age < 50 years at the time of diagnosis or had developed metachronous colorectal carcinoma. Whereas colon carcinoma in the proband implied an increased risk for both colon tumors and rectal tumors, the offspring of women who were diagnosed with rectal carcinoma were at increased risk of developing rectal carcinoma, but no significantly altered risk of colon carcinoma was observed. In the cohort, the cumulative risk for colorectal carcinoma before age 50 years was increased about 3.0 times compared with the general population.CONCLUSIONS: This report shows a significant familial aggregation of colorectal carcinoma, demonstrates possible differences in hereditary pattern between colon carcinoma and rectal carcinoma, and confirms that younger age at the time of diagnosis or the occurrence of metachronous tumors indicate familial carcinoma.
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| 27. |
- Salomonsson, Annette, et al.
(författare)
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Comprehensive analysis of RNA binding motif protein 3 (RBM3) in non-small cell lung cancer
- 2020
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Ingår i: Cancer Medicine. - : Blackwell Publishing Ltd. - 2045-7634. ; 9:15, s. 5609-5619
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Tidskriftsartikel (refereegranskat)abstract
- Aims High expression of the RNA-binding motif protein 3 (RBM3) correlates with improved prognosis in several major types of cancer. The aim of the present study was to examine the prognostic value of RBM3 protein and mRNA expression in non-small cell lung cancer (NSCLC).Methods and results Immunohistochemical expression of RBM3 was evaluated in surgically treated NSCLC from two independent patient populations (n = 213 and n = 306). Staining patterns were correlated with clinicopathological parameters, overall survival (OS), and recurrence-free interval (RFI). Cases with high nuclear RBM3 protein expression had a prolonged 5-year OS in both cohorts when analyzing adenocarcinomas separately (P = .02 and P = .01). RBM3 remained an independent prognostic factor for OS in multivariable analysis of cohort I (HR 0.44, 95% CI 0.21-0.90) and for RFI in cohort II (HR 0.38, 95% CI 0.22-0.74). In squamous cell carcinoma, there was instead an insignificant association to poor prognosis. Also, the expression levels of RBM3 mRNA were investigated in 2087 lung adenocarcinomas and 899 squamous cell carcinomas assembled from 13 and 8 public gene expression microarray datasets, respectively. The RBM3 mRNA levels were not clearly associated with patient outcome in either adenocarcinomas or squamous cell carcinomas.Conclusions The results from this study support that high protein expression of RBM3 is linked to improved outcome in lung adenocarcinoma.
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| 28. |
- Shahida, B., et al.
(författare)
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Simvastatin downregulates adipogenesis in 3T3-l1 preadipocytes and orbital fibroblasts from graves’ ophthalmopathy patients
- 2019
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Ingår i: Endocrine Connections. - 2049-3614. ; 8:9, s. 1230-1239
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Tidskriftsartikel (refereegranskat)abstract
- Background: Smoking is a strong risk factor for the development of Graves’ ophthalmopathy (GO). Immediate early genes (IEGs) are overexpressed in patients with active GO compared to healthy controls. The aim of this study was to study the effects of tobacco smoking and simvastatin on preadipocytes and orbital fibroblasts (OFs) in the adipogenic process. Methods: Cigarette smoke extract (CSE) was generated by a validated pump system. Mouse 3T3-L1 preadipocytes or OFs were exposed to 10% CSE with or without simvastatin. Gene expression was studied in preadipocytes and OFs exposed to CSE with or without simvastatin and compared to unexposed cells or cells treated with a differentiation cocktail. Results: In 3T3-L1 preadipocytes, Cyr61, Ptgs2, Egr1 and Zfp36 expression levels were two-fold higher in cells exposed to CSE than in unexposed cells. Simvastatin downregulated the expression of these genes (1.6-fold, 5.5-fold, 3.3-fold, 1.4-fold, respectively). CSE alone could not stimulate preadipocytes to differentiate. Scd1, Ppar-γ and adipogenesis were downregulated in simvastatin-treated preadipocytes compared to nontreated preadipocytes 18-, 35- and 1.7-fold, respectively. In OFs, similar effects of CSE were seen on the expression of CYR61 (1.4-fold) and PTGS2 (3-fold). Simvastatin downregulated adipogenesis, PPAR-γ (2-fold) and SCD (27-fold) expression in OFs. Conclusion: CSE upregulated early adipogenic genes in both mouse 3T3-L1 preadipocytes and human OFs but did not by itself induce adipogenesis. Simvastatin inhibited the expression of both early and late adipogenic genes and adipogenesis in preadipocytes and human OFs. The effect of simvastatin should be investigated in a clinical trial of patients with GO.
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| 29. |
- Shen, Sipeng, et al.
(författare)
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A multi-omic study reveals BTG2 as a reliable prognostic marker for early-stage non-small cell lung cancer
- 2018
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 12:6, s. 913-924
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Tidskriftsartikel (refereegranskat)abstract
- B-cell translocation gene 2 (BTG2) is a tumour suppressor protein known to be downregulated in several types of cancer. In this study, we investigated a potential role for BTG2 in early-stage non-small cell lung cancer (NSCLC) survival. We analysed BTG2 methylation data from 1230 early-stage NSCLC patients from five international cohorts, as well as gene expression data from 3038 lung cancer cases from multiple cohorts. Three CpG probes (cg01798157, cg06373167, cg23371584) that detected BTG2 hypermethylation in tumour tissues were associated with lower overall survival. The prognostic model based on methylation could distinguish patient survival in the four cohorts [hazard ratio (HR) range, 1.51-2.21] and the independent validation set (HR = 1.85). In the expression analysis, BTG2 expression was positively correlated with survival in each cohort (HR range, 0.28-0.68), which we confirmed with meta-analysis (HR = 0.61, 95% CI 0.54-0.68). The three CpG probes were all negatively correlated with BTG2 expression. Importantly, an integrative model of BTG2 methylation, expression and clinical information showed better predictive ability in the training set and validation set. In conclusion, the methylation and integrated prognostic signatures based on BTG2 are stable and reliable biomarkers for early-stage NSCLC. They may have new applications for appropriate clinical adjuvant trials and personalized treatments in the future.
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| 30. |
- Staaf, Johan, et al.
(författare)
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Diagnostic Value of Insulinoma-Associated Protein 1 (INSM1) and Comparison With Established Neuroendocrine Markers in Pulmonary Cancers : A Comprehensive Study and Review of the Literature
- 2020
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Ingår i: Archives of Pathology & Laboratory Medicine. - 0003-9985 .- 1543-2165. ; 144:9, s. 1075-1085
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Forskningsöversikt (refereegranskat)abstract
- Context.—The diagnostic distinction of pulmonary neuroendocrine (NE) tumors from non–small cell lung carcinomas (NSCLCs) is clinically relevant for prognostication and treatment. Diagnosis is based on morphology and immunohistochemical staining.Objective.—To determine the diagnostic value of insulinoma-associated protein 1 (INSM1), in comparison with established NE markers, in pulmonary tumors.Design.—Fifty-four pulmonary NE tumors and 632 NSCLCs were stained for INSM1, CD56, chromogranin A, and synaptophysin. In a subset, gene expression data were available for analysis. Also, 419 metastases to the lungs were stained for INSM1. A literature search identified 39 additional studies with data on NE markers in lung cancers from the last 15 years. Seven of these included data on INSM1.Results.—A positive INSM1 staining was seen in 39 of 54 NE tumors (72%) and 6 of 623 NSCLCs (1%). The corresponding numbers were 47 of 54 (87%) and 14 of 626 (2%) for CD56, 30 of 54 (56%) and 6 of 629 (1%) for chromogranin A, and 46 of 54 (85%) and 49 of 630 (8%) for synaptophysin, respectively. Analysis of literature data revealed that CD56 and INSM1 were the best markers for identification of high-grade NE pulmonary tumors when considering both sensitivity and specificity, while synaptophysin also showed good sensitivity. INSM1 gene expression was clearly associated with NE histology.Conclusions.—The solid data of both our and previous studies confirm the diagnostic value of INSM1 as a NE marker in pulmonary pathology. The combination of CD56 with INSM1 and/or synaptophysin should be the first-hand choice to confirm pulmonary high-grade NE tumors. INSM1 gene expression could be used to predict NE tumor histology.
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