Multi-colour FISH in oesophageal adenocarcinoma—predictors of prognosis independent of stage and grade

Geppert, Carol I.; Rümmele, Petra; Sarbia, Mario; Langer, Rupert; Feith, Marcus; Morrison, Larry E.; Pestova, Ekaterina; Schneider-Stock, R.; Hartmann, Arndt; Rau, Tilman T.

doi:10.1038/bjc.2014.238

Cited by 15 publications

(10 citation statements)

References 67 publications

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“…Geppert et al . [ 39 ] used FISH to demonstrate that the presence of chromosomal gain involving ZNF217 predicted stage-independent survival in 130 EAC patients. While based on copy number, these data are consistent with our mRNA findings.…”

Section: Discussionmentioning

confidence: 99%

Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas

et al. 2016

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The current high mortality rate of esophageal adenocarcinoma (EAC) reflects frequent presentation at an advanced stage. Recent efforts utilizing fluorescent peptides have identified overexpressed cell surface targets for endoscopic detection of early stage Barrett's-derived EAC. Unfortunately, 30% of EAC patients present with gastroesophageal junction adenocarcinomas (GEJAC) and lack premalignant Barrett's metaplasia, limiting this early detection strategy. We compared mRNA profiles from 52 EACs (tubular EAC; tEAC) collected above the gastroesophageal junction with 70 GEJACs, 8 normal esophageal and 5 normal gastric mucosa samples. We also analyzed our previously published whole-exome sequencing data in a large cohort of these tumors. Principal component analysis, hierarchical clustering and survival-based analyses demonstrated that GEJAC and tEAC were highly similar, with only modest differences in expression and mutation profiles. The combined expression cohort allowed identification of 49 genes coding cell surface targets overexpressed in both GEJAC and tEAC. We confirmed that three of these candidates (CDH11, ICAM1 and CLDN3) were overexpressed in tumors when compared to normal esophagus, normal gastric and non-dysplastic Barrett's, and localized to the surface of tumor cells. Molecular profiling of tEAC and GEJAC tumors indicated extensive similarity and related molecular processes. Identified genes that encode cell surface proteins overexpressed in both Barrett's-derived EAC and those that arise without Barrett's metaplasia will allow simultaneous detection strategies.

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Section: Discussionmentioning

confidence: 99%

Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas

et al. 2016

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“…Zi-Chao Zhang 1 , Li-Qiang Zheng 2 , Li-Jie Pan 1 , Jin-Xing Guo 1 , Guo-Shan Yang 1 * time after operation (Letessier et al, 2006). Moreover, the tumor-promoting action of ZNF217 was also reported in pancreatic cancer (Letessier et al, 2006), oesophageal adenocarcinoma (Geppert et al, 2014) and malignant glioma (Mao et al, 2011). However, the expression and functions of ZNF217 in human colorectal carcinoma were still absent of study.…”

Section: Znf217 Is Overexpressed and Enhances Cell Migration And Invasion In Colorectal Carcinomamentioning

confidence: 99%

ZNF217 is Overexpressed and Enhances Cell Migration and Invasion in Colorectal Carcinoma

Zhang¹,

Zheng²,

Pan³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: To investigate the expression and clinical significance of zinc finger protein 217 (ZNF217) in human colorectal carcinoma (CRC). Materials and Methods: The expression of ZNF217 in 60 CRC tissues and matched tumor adjacent tissues, collected between January 2013 and June 2014, was assessed immunohistochemically. The relationship between the expression of ZNF217 and clinicopathlogical features was analyzed by Pearson chi-square test. In addition, siRNA was used to down-regulate the expression of ZNF217 in CRC cells. The effects of ZNF217 for cell migration and invasion were measured by wound healing assay and transwell assay, respectively. Results: The expression level of ZNF217 was significantly higher in CRC tissues than in tumor adjacent tissues (p<0.05), positively correlating with tumor size, lymphatic metastasis and advanced TNM stage (p<0.05). Down-regulation of ZNF217 in CRC cells could significantly suppress cell migration and invasion. Conclusions: ZNF217 is overexpressed in colorectal carcinoma tissues and is associated with tumor malignant clinicopathological features. ZNF217 may promote CRC progression by inducing cell migration and invasion.

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“…Additionally, we have looked at the percentages of cells with greater than two gene or chromosome copies (gene or chromosome gain), or less than two copies (gene or chromosome loss), or the sum of these abnormal copy numbers (gene or chromosome gain or loss). This series of parameters is similar to those used in previous studies that compared different copy number parameters for associations with patient diagnoses and/or outcomes in melanoma [ 46 ], esophageal cancer [ 47 ], lung cancer [ 48 ], and cervical cancer [ 49 ]. This is the first application of these parameters in cases with neoadjuvant treatment of ERBB2-positive breast cancer.…”

Section: Discussionmentioning

confidence: 83%

MET and PTEN gene copy numbers and Ki-67 protein expression associate with pathologic complete response in ERBB2-positive breast carcinoma patients treated with neoadjuvant trastuzumab-based therapy

et al. 2016

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BackgroundPathologic complete response (pCR) after neoadjuvant chemotherapy for breast cancer is associated with improved prognosis in aggressive tumor subtypes, including ERBB2- positive tumors. Recent adoption of pCR as a surrogate endpoint for clinical trials in early stage breast cancer in the neoadjuvant setting highlights the need for biomarkers that, alone or in combination, help predict the likelihood of response to treatment.MethodsBiopsy specimens from 29 patients with invasive ductal carcinoma treated with trastuzumab-based therapy prior to definitive resection and pathologic staging were evaluated by dual color bright field in situ hybridization (dual ISH) using probes for MET, TOP2A, PTEN, and PIK3CA genes, each paired with centromeric probes to their respective chromosomes (chromosomes 7, 17, 10, and 3). Ki-67 expression was assessed by immunohistochemistry (IHC). Various parameters describing copy number alterations were evaluated for each gene and centromere probe to identify the optimal parameters for clinical relevance. Combinations of ISH parameters and IHC expression for Ki-67 were also evaluated.ResultsOf the four genes and their respective chromosomes evaluated by ISH, two gene copy number parameters provided statistically significant associations with pCR: MET gain or loss relative to chromosome 7 (AUC = 0.791, sensitivity = 92 % and specificity = 67 % at optimal cutoff, p = 0.0032) and gain of PTEN (AUC = 0.674, sensitivity = 38 % and specificity = 100 % at optimal cutoff, p = 0.039). Ki-67 expression was also found to associate significantly with pCR (AUC = 0.726, sensitivity = 100 % and specificity = 42 % at optimal cutoff, p = 0.0098). Combining gain or loss of MET relative to chromosome 7 with Ki-67 expression further improved the association with pCR (AUC = 0.847, sensitivity = 92 % and specificity = 83 % at optimal cutoffs, p = 0.0006).ConclusionsAn immunogenotypic signature of low complexity comprising MET relative copy number and Ki-67 expression generated by dual ISH and IHC may help predict pCR in ERBB2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab. These findings require validation in additional patient cohorts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2743-x) contains supplementary material, which is available to authorized users.

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Multi-colour FISH in oesophageal adenocarcinoma—predictors of prognosis independent of stage and grade

Cited by 15 publications

References 67 publications

Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas

Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas

ZNF217 is Overexpressed and Enhances Cell Migration and Invasion in Colorectal Carcinoma

MET and PTEN gene copy numbers and Ki-67 protein expression associate with pathologic complete response in ERBB2-positive breast carcinoma patients treated with neoadjuvant trastuzumab-based therapy

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