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

Abstract

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.

Lymph Node Positivity in One-Step Nucleic Acid Amplification is a Prognostic Factor for Postoperative Cancer Recurrence in Patients with Stage II Colorectal Cancer: A Prospective, Multicenter Study

“…Other studies also showed that pN0 CRC patients were up-staged by OSNA test in 15.3-28.8%. 13,15,24,25 It is suggested that difference of detection rate depends on sampling of LN volume and number. 24 Notably Rakislova et al 24 reported that 20.8% pN0 cases were OSNA-positive by the pooling method which would be helpful as compared to time consuming and expensive individual analysis of LNs.…”

“…Subsequent studies have further demonstrated the high sensitivity of OSNA in detecting LN metastasis of breast, gastric, lung, and colorectal cancers. [9][10][11][12][13][14][15][16] Our own previous prospective, multicenter studies conducted in Japan demonstrated the usefulness of the OSNA assay as a complementary tool for diagnosing LN metastasis and CRC staging. 17,18 The later study revealed that 17.6% (13/74) of patients with histologically node-negative stage II CRC were nodal positive by the OSNA assay.…”

Circulating Micro RNA- 21 and - 92a as Biomarkers of Colorectal Cancer

“…Colorectal cancer (CRC) is the third most common cancer diagnosed in both men and women [1]. The lifetime risk of developing CRC is about 1 in 21 (4.7%) for men and 1 in 23 (4.4%) for women.…”

“…The lifetime risk of developing CRC is about 1 in 21 (4.7%) for men and 1 in 23 (4.4%) for women. Many factors increase the risk including: obesity, diet high in red meat (such as beef, pork, lamb, or liver) and processed meat, smoking, heavy alcohol use, history of inflammatory bowel disease, family history of CRC or adenomatous polyps and diabetes mellitus [1]. Although colonoscopic screening for CRC is the most reliable tool; its difficulties and costs have hampered its wide application.…”

MicroRNA Expression in a Readily Accessible Common Hepatic Artery Lymph Node Predicts Time to Pancreatic Cancer Recurrence Postresection

“…In breast cancer and colorectal cancer, CK19 mRNA levels were shown to be useful for identifying lymph nodes that harbored metastatic cells. 23,24 While the expression of CK19 in Station 8 lymph nodes implies the presence of pancreatic cancer cells in these nodes, there was no difference in CK19 mRNA levels between patients with recurrent versus non-recurrent disease. By contrast, among the miRNAs examined in the current study, high levels of miRNA-10b, but not the other miRNAs currently investigated, were significantly increased in patients who developed cancer recurrence.…”