Molecular investigation of lymph nodes in colon cancer patients using one‐step nucleic acid amplification (OSNA)

Güller, Ulrich; Zettl, Andreas; Worni, Mathias; Langer, Igor; Cabalzar-Wondberg, Daniela; Viehl, Carsten T.; Demartines, Nicolas; Zuber, Markus

doi:10.1002/cncr.27667

Cited by 67 publications

(72 citation statements)

References 27 publications

(74 reference statements)

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“…These findings confirm the technical feasibility of lymph node staging of colon carcinoma patients as recently described (Croner et al , 2010; Guller et al , 2012; Yamamoto et al , 2013). OSNA appears to be a more accurate method of staging colon carcinoma patients, and identifies pN0 individuals who may benefit from adjuvant treatment.…”

Section: Discussionsupporting

confidence: 90%

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Molecular staging of lymph node-negative colon carcinomas by one-step nucleic acid amplification (OSNA) results in upstaging of a quarter of patients in a prospective, European, multicentre study

et al. 2014

Br J Cancer

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Background:Current histopathological staging procedures in colon carcinomas depend on midline division of the lymph nodes with one section of haematoxylin & eosin (H&E) staining only. By this method, tumour deposits outside this transection line may be missed and could lead to understaging of a high-risk group of stage UICC II cases, which recurs in ∼20% of cases. A new diagnostic semiautomated system, one-step nucleic acid amplification (OSNA), detects cytokeratin (CK) 19 mRNA in lymph node metastases and enables the investigation of the whole lymph node. The objective of this study was to assess whether histopathological pN0 patients can be upstaged to stage UICC III by OSNA.Methods:Lymph nodes from patients who were classified as lymph node negative after standard histopathology (single (H&E) slice) were subjected to OSNA. A result revealing a CK19 mRNA copy number >250, which makes sure to detect mainly macrometastases and not isolated tumour cells (ITC) or micrometastases only, was regarded as positive for lymph node metastases based on previous threshold investigations.Results:In total, 1594 pN0 lymph nodes from 103 colon carcinomas (median number of lymph nodes per patient: 14, range: 1–46) were analysed with OSNA. Out of 103 pN0 patients, 26 had OSNA-positive lymph nodes, resulting in an upstaging rate of 25.2%. Among these were 6/37 (16.2%) stage UICC I and 20/66 (30.3%) stage UICC II patients. Overall, 38 lymph nodes were OSNA positive: 19 patients had one, 3 had two, 3 had three, and 1 patient had four OSNA-positive lymph nodes.Conclusions:OSNA resulted in an upstaging of over 25% of initially histopathologically lymph node-negative patients. OSNA is a standardised, observer-independent technique, allowing the analysis of the whole lymph node. Therefore, sampling bias due to missing investigation of certain lymph node tissue can be avoided, which may lead to a more accurate staging.

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Section: Discussionsupporting

confidence: 90%

“…Patients recruited for this study were not included in recent single-institutional investigations demonstrating the accuracy of OSNA for lymph node staging in colorectal carcinomas (Croner et al , 2010; Guller et al , 2012). …”

mentioning

confidence: 99%

Molecular staging of lymph node-negative colon carcinomas by one-step nucleic acid amplification (OSNA) results in upstaging of a quarter of patients in a prospective, European, multicentre study

et al. 2014

Br J Cancer

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“…Compared with intensive histopathology, OSNA had 94.5% sensitivity, 97.6% specificity and a concordance rate of 97.1%. OSNA resulted in an upstaging of 2 of 13 patients (15.3%) with LNN colon cancer after standard HE examination [73]. However, this needs to be replicated and validated in other studies before clinical utility can be recommended.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, a novel diagnostic system, called one-step nucleic acid amplification (OSNA), has been designed to detect cytokeratin 19 (CK-19) mRNA as a surrogate for lymph node metastases. In one study [73], half of each lymph node was analyzed initially by HE followed by an intensive histologic workup (5 levels of HE and IHC analyses, the gold standard for the assessment of sensitivity/specificity of OSNA), and the other half was analyzed using OSNA. Compared with intensive histopathology, OSNA had 94.5% sensitivity, 97.6% specificity and a concordance rate of 97.1%.…”

Section: Resultsmentioning

confidence: 99%

Qualitative and Quantitative Issues of Lymph Nodes as Prognostic Factor in Colon Cancer

Veen¹,

Nedrebø²,

Stormark³

et al. 2013

Dig Surg

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For patients undergoing curative resections for colon cancer, the nodal status represents the strongest prognostic factor, yet at the same time the most disputed issue as well. Consequently, the qualitative and quantitative aspects of lymph node evaluation are thus being scrutinized beyond the blunt distinction between ‘node positive' (pN+) and ‘node negative' (pN0) disease. Controversy ranges from a minimal or ‘least-unit' strategy as exemplified by the ‘sentinel node' to a maximally invasive or ‘all inclusive' approach by extensive surgery. Ranging between these two extremes of node sampling strategies are factors of quantitative and qualitative value, which may be subject to modification. Qualitative issues may include aspects of lymph node harvest reflected by surgeon, pathologist and even hospital performance, which all may be subject to modification. However, patient's age, gender and genotype may be non-modifiable, yet influence node sample. Quantitative issues may reflect the balance between absolute numbers and models investigating the relationships of positive to negative nodes (lymph node ratio; log odds of positive lymph nodes). This review provides an updated overview of the current controversies and a state-of-the-art perspective on the qualitative and quantitative aspects of using lymph nodes as a prognostic marker in colon cancer.

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“…Classification of CRC is referred to their pathological stage, which can be observed after surgery [2]. The clinical and the pathological stages may be different, as the imaging tests can be different from the observed stage after surgery.…”

Section: An Introduction On Colorectal Cancermentioning

confidence: 99%

General Aspects of Colorectal Cancer

Centelles

2012

ISRN Oncology

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Colorectal cancer (CRC) is one of the main causes of death. Cancer is initiated by several DNA damages, affecting proto-oncogenes, tumour suppressor genes, and DNA repairing genes. The molecular origins of CRC are chromosome instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). A brief description of types of CRC cancer is presented, including sporadic CRC, hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndromes, familiar adenomatous polyposis (FAP), MYH-associated polyposis (MAP), Peutz-Jeghers syndrome (PJS), and juvenile polyposis syndrome (JPS). Some signalling systems for CRC are also described, including Wnt-β-catenin pathway, tyrosine kinase receptors pathway, TGF-β pathway, and Hedgehog pathway. Finally, this paper describes also some CRC treatments.

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Molecular investigation of lymph nodes in colon cancer patients using one‐step nucleic acid amplification (OSNA)

Cited by 67 publications

References 27 publications

Molecular staging of lymph node-negative colon carcinomas by one-step nucleic acid amplification (OSNA) results in upstaging of a quarter of patients in a prospective, European, multicentre study

Molecular staging of lymph node-negative colon carcinomas by one-step nucleic acid amplification (OSNA) results in upstaging of a quarter of patients in a prospective, European, multicentre study

Qualitative and Quantitative Issues of Lymph Nodes as Prognostic Factor in Colon Cancer

General Aspects of Colorectal Cancer

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