Abstract
BackgroundAccording 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.MethodsBM 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.ResultsIn 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).ConclusionsThese 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.
Highlights
Prognosis of patients with colon cancer is still limited despite improved surgical techniques, guidelines to assure an adequate lymph node yield and multimodal oncological therapy
This study examines the relationship of isolated tumour cells (ITC) in sentinel lymph nodes (SLN) and bone marrow micrometastases (BMM) in patients in early CC
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
Summary
Prognosis of patients with colon cancer is still limited despite improved surgical techniques, guidelines to assure an adequate lymph node yield and multimodal oncological therapy. LN with ITC on the other hand are harbouring either single tumour cells or clusters of tumour cells of B 0.2 mm and are considered as negative LN (pN0(i ?)) [10] Despite their small size, ITC have been reported to impact survival in early stage colon cancer [11, 12]. ITC have been reported to impact survival in early stage colon cancer [11, 12] These ‘‘occult’’ metastases are difficult to find with standard histopathological techniques, and it has been demonstrated that sentinel lymph node (SLN) mapping with multilevel sectioning and immunohistochemical staining improves their detection rates [6, 13]. 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. The correlation between the occurrence of ITC? and BMM? and their effects on survival was examined using Cox regression analysis
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