Tumor cell dissemination in colon cancer does not predict extrahepatic recurrence in patients undergoing surgery for hepatic metastases

Abstract

Abstract. Patients undergoing resection of hepatic metastases of colorectal cancer have a high risk of extrahepatic recurrence, most likely caused by early tumor cell dissemination or the manipulation of liver tumors during surgical resection. Using immunocytochemistry, we studied 47 patients for cytokeratin (CK)-positive (+) cells in: a) bone marrow (BM) samples to determine whether tumor cell dissemination had already occurred before surgery; and b) blood samples directly taken from the hepatic vein before and during surgery of liver metastases. In addition, normal and malignant liver tissues were evaluated for markers known to be involved in tumor progression and metastasis [urokinase plasminogen activator (uPA), Her-2/neu, epidermal growth factor receptor (EGF-R)] using sandwich enzyme immunoassays. CK + cells were detected in the BM of 26/47 patients (55%), in blood samples of 14/47 patients (30%) before surgery and 11/47 patients (23%) during surgery with a median detection rate of 1 (range, 1-14) CK + cell per 4x10 6 MNC. No CK + cells were found in 15/47 patients (32%) in any sample studied. Tumor tissue was obtained from 32/47 patients and normal liver tissue from 24/32 patients. While no differences were found for EGF-R and Her-2/neu, a 9-fold higher expression of uPA could be demonstrated in tumor tissue of 20/32 patients (63%) compared to normal liver tissue. When all obtained results were correlated with clinical outcome, neither the detection of CK + cells nor the expression pattern in the tumor tissue, or the combination of both, was predictive for extrahepatic recurrence or overall survival after a mean observation time of 43 months (range, 26-54 months). Although uPa is overexpressed in liver metastases of colorectal cancer, and dissemination of CK + cells during surgery of these metastases is a frequent event in colon cancer, these findings do not predict extrahepatic recurrence. Further characterization of single cells, especially those spread during surgery, will help to identify those patients with an increased risk of later relapse.

Use of a leucocyte filter to remove tumour cells from intra‐operative cell salvage blood

“…Using an immunohistochemical labelling method, Hansen and colleagues found that tumour cells were detectable in the peripheral blood of 26% of surgical patients at the time of tumour surgery [29]. There is, however, debate about whether such circulating tumour cells are of pathological significance [30][31][32]. Schoppmeyer in 2006 [32] using a similar immunohistochemical labelling method to ours, prospectively studied 47 patients with colonic cancer before and during surgery.…”

“…There is, however, debate about whether such circulating tumour cells are of pathological significance [30][31][32]. Schoppmeyer in 2006 [32] using a similar immunohistochemical labelling method to ours, prospectively studied 47 patients with colonic cancer before and during surgery. Cytokeratin-labelled (CK+) cells were detected in the bone marrow of 26 patients (55%) and in blood samples of 14 patients (30%) before surgery and 11 patients (23%) during surgery with a median detection rate of 1 (range, 1-14) CK+ cell per 4 · 10 6 mononuclear cells.…”

Review: Biological relevance of disseminated tumor cells in cancer patients

“…145,152 In contrast, 3 other reports, mostly on smaller patient cohorts, could not detect any association between prognostic factors and the presence of DTC. 146,147,153 To date, CK20 is the most commonly used marker in RT-PCR analyses of BM from CRC patients (Table II), with more than 10 studies published so far. However, only in 3 studies the number of investigated patients was larger than 100 with DTC detection rates of 11-35%.…”

Cytokeratin 18 (CK18) and CK18 Fragments for Detection of Minimal Residual Disease in Colon Cancer Patients

“…A similar result was published by Wind et al for the respective type of operative procedures, revealing that the cumulative percentage of samples containing CTCs was significantly higher during open surgery as compared to the laparoscopic approach (Wind et al, 2009). However, dissemination of CK + cells during surgery of hepatic metastases, a frequent event in colon cancer patients, did not predict extrahepatic recurrence (Schoppmeyer et al, 2006, Koch et al, 2007. In conclusion, CTCs seem to be generated during surgery; however, their significance for the occurrence of relapses is not clear.…”