scholarly journals The Simultaneous Presence of Isolated Tumour Cells and Bone Marrow Micrometastases in Stage I and II Colon Cancer—Challenging the Theory of a Chronological Pathway of Tumour Cell Dissemination

2021 ◽  
Author(s):  
Michaela Ramser ◽  
Rene Warschkow ◽  
Carsten T. Viehl ◽  
Christoph Kettelhack ◽  
Andreas Zettl ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Colon Cancer ◽  
Tumour Progression ◽  
Tumour Cells ◽  
Stage I ◽  
Cox Regression Analysis ◽  
Tumour Spread ◽  
Bone Marrow Micrometastases ◽  
Isolated Tumour Cells ◽  
The Common

Abstract Background According to the common tenet, tumour progression is a chronological process starting with lymphatic invasion. In this respect, the meaning of bone marrow micrometastases (BMM) in patients with lymph node negative colon cancer (CC) is unclear. This study examines the relationship of isolated tumour cells (ITC) in sentinel lymph nodes (SLN) and BMM in patients in early CC. Methods BM aspirates were taken from both pelvic crests and in vivo SLN mapping was done during open oncologic colon resection in patients with stage I and II CC. Stainings were performed with the pancytokeratin markers A45-B/B3 and AE1/AE3 as well as H&E. The correlation between the occurrence of ITC+ and BMM+ and their effects on survival was examined using Cox regression analysis. Results In a total of 78 patients with stage I and II CC, 11 patients (14%) were ITC+, 29 patients (37%) BMM+. Of these patients, only two demonstrated simultaneous ITC+ /BMM+. The occurrence of BMM+ was neither associated with ITC+ in standard correlation (kappa = − 0.13 [95% confidence interval [CI] = − 0.4–0.14], p = 0.342) nor univariate (odds ratio [OR] = 0.39, 95%CI:0.07–1.50, p = 0.180) or multivariate (OR = 0.58, 95%CI: 0.09–2.95, p = 0.519) analyses. Combined detection of ITC+ /BMM+ demonstrated the poorest overall (HR = 61.60, 95%CI:17.69–214.52, p = 0.032) and recurrence free survival (HR = 61.60, 95%CI: 17.69–214.5, p = 0.032). Conclusions These results indicate that simultaneous and not interdependent presence of very early lymphatic and haematologic tumour spread may be considered as a relevant prognostic risk factor for patients with stage I and II CC, thereby suggesting the possible need to reconsider the common assumptions on tumour spread proposed by the prevalent theory of sequential tumour progression.

Disseminated tumour cells in bone marrow in experimental colon cancer: metastatic or resident?

2013 ◽  
Vol 15 (6) ◽  
pp. 667-673 ◽  
Author(s):  
M. Barone ◽  
D. F. Altomare ◽  
M. T. Rotelli ◽  
M. P. Scavo ◽  
D. Piscitelli ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Colon Cancer ◽  
Tumour Cells ◽  
Disseminated Tumour Cells

Long-term follow-up of bone marrow micrometastases in colon cancer patients.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 3529-3529
Author(s):  
Carsten T. Viehl ◽  
Ulrich Guller ◽  
Michaela Ramser ◽  
Salome Dell-Kuster ◽  
Benjamin Weixler ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Colon Cancer ◽  
Cancer Patients ◽  
Bone Marrow Micrometastases ◽  
Long Term Follow Up

scholarly journals Cyclin A2 Protein Overexpression Is Not Caused by Gene Amplification in Colon Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Lise Aagaard Sørby ◽  
Kristin Jonsdottir ◽  
Klaus Beiske ◽  
Peter Blom ◽  
Ida Rashida Khan Bukholm ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Real Time ◽  
Real Time Pcr ◽  
Tumour Cells ◽  
Tumour Tissue ◽  
Chromosome 4 ◽  
Tissue Samples ◽  
Breast Tumours ◽  
Isolated Tumour Cells ◽  
Cyclin A2

Increased expression of cyclin A2 protein has been detected in different types of cancers. However, its prognostic importance appears to differ between tumours. The significance and precise mechanisms behind cyclin A2 overexpression remain to be elucidated. We used real-time PCR to examine CCNA2 amplification in tumour cells isolated by laser microdissection and in total tumour tissue in colon cancer patients in which overexpression of cyclin A2 protein had been revealed by immunohistochemistry (n=22 patients). The results were verified by FISH. CCNA2 amplification was not detected in either the isolated tumour cells or the total tumour tissue. We verified our methods by demonstrating amplification of CCNA2 by real-time PCR in three out of eight breast tumours that overexpressed cyclin A2 protein (this frequency is consistent with the findings of others). However, FISH did not reveal any CCNA2 amplification in the breast tumours, but it did reveal polysomy of chromosome 4 or segments of chromosome 4 in three tumour tissue samples, indicating the importance of verifying the real-time PCR results with another method. To conclude, the increased cyclin A2 protein expression in these patients could not be explained by CCNA2 amplification in isolated colonic tumour cells.

Cytokeratin (CK)-positive bone marrow micrometastases (BMM) and survival in stage I-III breast cancer

1999 ◽  
Vol 35 ◽  
pp. S84
Author(s):  
S. Braun ◽  
K. Pantel ◽  
W. Janni ◽  
F. Hepp ◽  
C.R.M. Kentenich ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Stage I ◽  
Bone Marrow Micrometastases

scholarly journals Cytokeratin-positive cells in the bone marrow from patients with pancreatic, periampullary malignancy and benign pancreatic disease show no prognostic information

2020 ◽  
Author(s):  
Harald Hugenschmidt ◽  
Knut Jørgen Labori ◽  
Cathrine Brunborg ◽  
Caroline Sophie Verbeke ◽  
Lars Thomas Seeberg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Advanced Disease ◽  
Pancreatic Disease ◽  
Benign Disease ◽  
Tumour Cells ◽  
Prognostic Impact ◽  
Periampullary Carcinoma ◽  
Cox Regression Analysis ◽  
Entire Cohort

Abstract Background: Pancreatic and periampullary carcinoma are aggressive tumours where preoperative assessment is challenging. Disseminated tumour cells (DTC) in the bone marrow (BM) are associated with impaired prognosis in a variety of epithelial cancers. In a cohort of patients with presumed resectable pancreatic and periampullary carcinoma, we evaluated the frequency and the potential prognostic impact of the preoperative presence of DTC, defined as cytokeratin-positive cells detected by immunocytochemistry (ICC).Methods: Preoperative BMsamples from 242 patients selected for surgical resection of presumed resectable pancreatic and periampullary carcinoma from 09/2009 to 12/2014, were analysed for presence of CK-positive cells by ICC. The median observation time was 21.5 months. Overall survival (OS) and disease-free survival (DFS) were calculated by Kaplan-Meier and Cox regression analysis.Results: Successful resections of malignant tumours were performed in 179 of the cases, 30 patients resected had benign pancreatic disease based on postoperative histology, and 33 were deemed inoperable intraoperatively due to advanced disease. Overall survival for patients with resected carcinoma was 21.1 months (95% CI: 18.0-24.1), for those with benign disease OS was 101 months (95% CI: 69.4-132) and for those with advanced disease OS was 8.8 months (95% CI: 4.3-13.3). The frequency of CK-positive cells was 6/168 (3.6%) in resected malignant cases, 2/31 (6.5%) in advanced disease and 4/29 (13.8%) in benign disease. The presence of CK-positive cells was not correlated to OS or DFS, neither in the entire cohort nor in the subgroup negative for circulating tumour cells (CTC). Conclusions: The results indicate that CK-positive cells may be present in both patients with malignant and benign diseases of the pancreas. Detection of CK-positive cells was not associated with differences in prognosis for the entire cohort or any of the subgroups analysed.Trial registration: clinicaltrials.gov (NCT01919151)

Immunocytochemical detection of isolated tumour cells in bone marrow of patients with untreated stage C prostatic cancer

1995 ◽  
Vol 31 (10) ◽  
pp. 1627-1632 ◽  
Author(s):  
K. Pantel ◽  
C. Aignherr ◽  
J. Köllermann ◽  
J. Caprano ◽  
G. Riethmüller ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Prostatic Cancer ◽  
Tumour Cells ◽  
Immunocytochemical Detection ◽  
Isolated Tumour Cells

scholarly journals Circular RNA in Chemonaive Lymph Node Negative Colon Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1903
Author(s):  
Inge van den Berg ◽  
Marcel Smid ◽  
Robert R. J. Coebergh van den Braak ◽  
Carolien H. M. van Deurzen ◽  
Vanja de Weerd ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cox Regression ◽  
Multiple Correspondence Analysis ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Stage I ◽  
Circular Rnas ◽  
Curative Surgery ◽  
Cox Regression Analysis ◽  
High Diversity

Circular RNAs (circRNAs) appear important in tumor progression of colon cancer (CC). We identified an extensive catalog of circRNAs in 181 chemonaive stage I/II colon tumors, who underwent curative surgery between 2007 and 2014. We identified circRNAs from RNAseq data, investigated common biology related to circRNA expression, and studied the association between circRNAs and relapse status, tumor stage, consensus molecular subtypes (CMS), tumor localization and microsatellite instability (MSI). We identified 2606 unique circRNAs. 277 circRNAs (derived from 260 genes) were repeatedly occurring in at least 20 patients of which 153 showed a poor or even negative (R < 0.3) correlation with the expression level of their linear gene. The circular junctions for circSATB2, circFGD6, circKMT2C and circPLEKHM3 were validated by Sanger sequencing. Multiple correspondence analysis showed that circRNAs were often co-expressed and that high diversity in circRNAs was associated with favorable disease-free survival (DFS), which was confirmed by Cox regression analysis (Hazard Ratio (HR) 0.60, 95% CI 0.38–0.97, p = 0.036). Considering individual circRNAs, absence of circMGA was significantly associated with relapse, whereas circSATB2, circNAB1, and circCEP192 were associated with both MSI and CMS. This study represents a showcase of the potential clinical utility of circRNAs for prognostic stratification in patients with stage I–II colon cancer and demonstrated that high diversity in circRNAs is associated with favorable DFS.

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