The Relationship between the Presence of Chromosomal Instability and Prognosis of Squamous Cell Carcinoma of the Lung: Fluorescence in situ Hybridization Analysis of Paraffin-embedded Tissue from 47 Korean Patients

Yoo, Jung‐Wan; Seo, Kwang Won; Jang, Se Jin; Oh, You Na; Shim, Tae Sun; Kim, Woo Sung; Lee, Dong-Soon; Lee, Sang‐Do; Choi, Chang‐Min

doi:10.3346/jkms.2010.25.6.863

Cited by 15 publications

(13 citation statements)

References 19 publications

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“…For instance, increased copy number in EGFR, MYC, 5p15.2 and centromere 6 and deletion in TP16 detected by FISH was associated with poor overall survival rate in lung squamous cell carcinoma. 31 Deletions in 3p detected by comparative genomic hybridization were associated with decreased overall survival in lung squamous cell carcinomas independent of clinicopathological parameters. 32 …”

Section: Discussionmentioning

confidence: 97%

Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer

Barón

Kako

Feser

et al. 2017

Journal of Thoracic Oncology

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Introduction Low dose CT screening for lung cancer has a high false positive rate with frequent discovery of indeterminate pulmonary nodules. Noninvasive biomarkers are needed to reduce false positives and improve risk stratification. A retrospective longitudinal evaluation was performed to assess chromosomal aneusomy in sputum via fluorescence in situ hybridization (CA-FISH) in four nested case-control studies. Methods ROC analysis resulted in two grouped cohorts: High Risk (CO High Risk and CO Nodule; 68 Cases, 69 controls) and Screening (ACRIN/NLST and PLuSS; 97 Cases, 185 controls). The CA-FISH assay was a 4-target DNA panel encompassing EGFR and MYC genes, and the 5p15 and centromere 6 regions or the FGFR1 and PIK3CA genes. A 4-category scale: normal, probably normal, probably abnormal and abnormal was applied. Sensitivity, specificity, and positive and negative likelihood ratios (LR+, LR−) (with 95% CI) were estimated for each cohort. Results Sensitivity and specificity were, respectively, 0.67 (0.55, 0.78) and 0.94 (0.85, 0.98) for High Risk subjects and 0.20 (0.13, 0.30) and 0.84 (0.78, 0.89) for Screening subjects. LR+ and LR− were, respectively, 11.66 (4.44, 30.63) and 0.34 (0.24, 0.48) for High Risk; and 1.36 (0.81, 2.28) and 0.93 (0.83, 1.05) for Screening subjects. Conclusion The high positive likelihood ratio of sputum CA-FISH indicates it could be a useful adjunct to LDCT for lung cancer in high risk settings. For screening, however, its low positive likelihood ratio limits clinical utility. Prospective assessment of CA-FISH in the incidentally-identified indeterminate nodule setting is ongoing in the Colorado Pulmonary Nodule Biomarker Trial.

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Section: Discussionmentioning

confidence: 97%

Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer

Barón

Kako

Feser

et al. 2017

Journal of Thoracic Oncology

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“…Aneuploidy has prognostic relevance in multiple cancer types (Carter et al., 2006, Danielsen et al., 2016, Kronenwett et al., 2004, Mouradov et al., 2013, Yoo et al., 2010) and is associated with cancer multidrug resistance (Kuznetsova et al., 2015, Lee et al., 2011, Swanton et al., 2006). These high-risk features of CIN suggest that targeting aneuploid cancer cell populations may have therapeutic potential, emphasizing the importance of understanding the cellular processes that initiate and promote tolerance of aneuploidy.…”

Section: Discussionmentioning

confidence: 99%

BCL9L Dysfunction Impairs Caspase-2 Expression Permitting Aneuploidy Tolerance in Colorectal Cancer

et al. 2017

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SummaryChromosomal instability (CIN) contributes to cancer evolution, intratumor heterogeneity, and drug resistance. CIN is driven by chromosome segregation errors and a tolerance phenotype that permits the propagation of aneuploid genomes. Through genomic analysis of colorectal cancers and cell lines, we find frequent loss of heterozygosity and mutations in BCL9L in aneuploid tumors. BCL9L deficiency promoted tolerance of chromosome missegregation events, propagation of aneuploidy, and genetic heterogeneity in xenograft models likely through modulation of Wnt signaling. We find that BCL9L dysfunction contributes to aneuploidy tolerance in both TP53-WT and mutant cells by reducing basal caspase-2 levels and preventing cleavage of MDM2 and BID. Efforts to exploit aneuploidy tolerance mechanisms and the BCL9L/caspase-2/BID axis may limit cancer diversity and evolution.

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“…The replication stress induced by the gain of chromosome in the nucleus may lead to genomic instability (GIN) which contributes to tumorigenesis [ 15 , 16 , 17 , 18 ]. Aneuploidy is positively associated with inherent or acquired chemotherapeutic drug resistance [ 15 , 19 , 20 , 21 ]. The aneuploidy was reported as an independent marker for the recurrence of colon cancer [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Detection of Circulating Tumor Cells Using Negative Enrichment Immunofluorescence and an In Situ Hybridization System in Pancreatic Cancer

Qin

et al. 2017

IJMS

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Pancreatic cancer (PC) is the most lethal type of gastrointestinal cancer, and early detection and monitoring is an urgent problem. Circulating tumor cells (CTCs) are emerging as a non-invasive biomarker for tumor detection. However, the low sensitivity is a main problem in the traditional CellSearch System for detecting CTCs, especially in patients with PC. In this study, we used negative enrichment (NE), immunofluorescence and in situ hybridization (FISH) of chromosome 8 (NE-iFISH) to capture and identify CTCs in PC patients. We showed that the NE-iFISH system exhibited a dramatically high detection rate of CTCs in PC patients (90%). The diagnostic rate of PC reached 97.5% when combining CTCs ≥ 2 and carbohydrate antigen 19-9 (CA19-9) > 37 µmol/L. The 1-year survival in the group of CTCs < 3 was significantly higher than that of CTCs ≥ 3 (p = 0.043). In addition, we analyzed the role of chromosomal instability in CTCs detection. The group of triploid (three hybridization signals of chromosome 8) CTCs ≥ 3 showed a shorter 1-year survival (p = 0.0279) and overall survival (p = 0.0188) than the group with triploid CTCs < 3. Importantly, the triploid CTC number but not the overall CTC counts could be a predictor of chemo-sensitivity. Moreover, circulating tumor microembolus (CTMs) were found in stage IV patients, and were positively related to the poor response to chemotherapy. In conclusion, the NE-iFISH system significantly improved the positive detection rate of CTCs and triploid CTC could be used to predict prognosis or the response to the chemotherapy of PC patients. CTM is a potential indicator of the chemotherapeutic effect in advanced PC patients.

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The Relationship between the Presence of Chromosomal Instability and Prognosis of Squamous Cell Carcinoma of the Lung: Fluorescence in situ Hybridization Analysis of Paraffin-embedded Tissue from 47 Korean Patients

Cited by 15 publications

References 19 publications

Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer

Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer

BCL9L Dysfunction Impairs Caspase-2 Expression Permitting Aneuploidy Tolerance in Colorectal Cancer

Detection of Circulating Tumor Cells Using Negative Enrichment Immunofluorescence and an In Situ Hybridization System in Pancreatic Cancer

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