Prognostic Impact of CK‐20‐positive Cells in Peripheral Venous Blood of Patients with Gastrointestinal Carcinoma

Abstract

Despite curative tumor resection, about 30%-50% of patients with locally advanced gastrointestinal (GI) carcinoma develop tumor recurrence which may be caused by pre- or intraoperative tumor cell dissemination. We examined the combination of optimized density gradient centrifugation with a CK-20 reverse transcriptase-polymerase chain reaction to detect and quantify circulating tumor cells in peripheral blood. Peripheral venous blood (20 ml) of patients with GI carcinomas was collected during primary tumor staging before and after the endoscopy procedure. CK-20 expression in peripheral venous blood was found in 22 of 82 patients (26.8%) with a nonsignificant difference between the upper GI tract (23.9%) and the lower GI tract (30.5%). The correlation with clinical outcome (24-month-survival) revealed a significantly worse prognosis (p < 0.05) of CK-20-positive patients with carcinoma of the upper GI tract and a trend toward a worse prognosis for patients with carcinoma of the lower GI tract. Quantification of CK-20 expression in peripheral blood showed a significantly higher circulating CK-20 copy number (median: 2816) in patients with metastatic tumors than in those with non-metastatic tumors (median: 983) (p < 0.05). For a subset of 42 primarily operated patients, we correlated the detection rate with UICC (International Union Against Cancer) staging categories. In contrast to the upper GI tract, the detection rate of patients with carcinoma of the lower GI tract showed a trend toward tumor size (pT) and a significant correlation with the presence of distant metastases (pM) (p < 0.01) and the postoperative residual tumor status (R) (p < 0.01). The endoscopy procedure did not lead to an increased detection of CK-20 expression.

Comparative Analysis of Tumor Markers and Evaluation of Their Predictive Value in Patients with Colorectal Cancer

“…Pre-and postoperative serum CEA levels have been correlatedwiththeUICCstageofatumor [4].Patientswith metastatic tumors had significantly higher CK20 mRNA levelsintheperipheralbloodthanthosewithnon-metastatic tumors [5]. Our data agreed with these reports, as stage IV CRCpatientshadsignificantlyhigherlevelsofCEAmRNA, CK20 mRNA, and serum CEA than stage I-III patients.…”

“…[17], and CEA mRNA levels are more predictive of tumor recurrence in esophageal cancer than serum CEA protein levels [18]. Our data agrees with recent RT-PCR studies showingthatpatientspositiveforCEAorCK20mRNAhada significantlypoorerprognosisthanpatientsnegativeforthese markers [3,5,19]. HighlevelsofpreoperativeCEAareasignificantnegative prognosticmarkerforreducedoverallsurvivalaftersurgical resection of colorectal carcinomas [8,9,15], though CEA mRNA was not predictive for the development of hepatic metastasis [20].AlthoughCEAandCK20mRNAlevelswere higher in colorectal tumors when compared to non-tumor tissue, they were not related to staging or clinical development [21].PostoperativeCEAlevels,butnotCA19-9orp53 levels, were a significant prognostic factor for disease-free survivalofCRCpatients [22].Ourstudypopulationincluded 27postoperativepatientsand19patientswithorganmetasta-sesthatcouldnotbesurgicallyremoved.Patientspositivefor CEA mRNA had significantly shorter survival curves than thosenegativeforCEAmRNA,thoughCK20mRNA,serum CEAproteinlevels,andserumCA19-9proteinlevelshadno correlationwithoverallsurvival.Wesuggestthatthiscouldbe due to i) the small study population or ii) admixture of patientsatdifferentstagesofthedisease.WenotedthatCEA mRNAwashigherinstageIpatientsthaninstageIIpatients andwaspresentinsomeofthehealthyvolunteers,thoughwe donotcurrentlyhaveanexplanationforthis.However,CRC diagnosiswasnotbasedonCEAmRNAlevelsbutonpathologicalfindings.…”

Development of a high‐throughput membrane‐array method for molecular diagnosis of circulating tumor cells in patients with gastric cancers

“…In the literature, the presence of CTCs in the peripheral blood has been reported to be associated with malignant biological properties, more advanced disease and poor prognosis of GC patients. [12][13][14]30 Similarly, our results showed that the frequency of hTERT, CK-19, CEA and MUC1 mRNA overexpression were significantly higher in advanced GC patients (82.8-87.9%) than in patients with early stage GC (33.3-50%). Moreover, the detection rates for CTCs in GC patients by using single markers CK-19, CEA or MUC1 mRNA were prominently higher in GC patients with stage III and IV GC than in patients with stage I and II GC.…”

“…21 RT-PCR assay is by far regarded widely to be the most sensitive method for detecting tumor-associated molecular markers. [26][27][28][29][30][31][32] However, for multiple gene detection, RT-PCR is too time-consuming and laborious to apply in clinical diagnosis. Accordingly, the present study focused on the diagnostic advantage and utility of high-throughput, multimarker membrane array for the detection of CTCs spread from primary GC.…”

Lymphadenectomy in colorectal cancer: does it make a difference?

“…This resection includes the regional lymphatic drainage region along the blood supply (systematic lymphadenectomy) [1][2][3]. Resection should be performed with a ''no-touch'' technique, because past experience has shown that intraoperative mechanical tumor manipulation can release disseminated tumor cells into the bloodstream [4].…”