Prognostic significance of EpCAM-positive disseminated tumor cells in rectal cancer patients with stage I disease.
Here we evaluated the prevalence and prognostic impact of epithelial cell adhesion molecule (EpCAM)-positive disseminated tumor cells (DTCs) in stage I rectal cancer. Further we tested the association of these single tumor cells or small tumor cell groups with the extent of peritumoral lymphangiogenesis. A total of 845 regional lymph nodes (LN) of 44 patients classified as negative on conventional histopathology were retrospectively reanalyzed with immunohistochemistry (IHC) using the monoclonal antibody Ber-Ep4 directed against EpCAM for the detection of DTCs. The degree of lymphangiogenesis in the primary tumors was assessed by IHC of the primary tumor tissue using the monoclonal antibody D2-40, which reacts with the lymphatic endothelium. The IHC results were correlated with clinico-pathologic parameters and clinical follow-up data. EpCAM-positive DTCs in LNs were detected in 8 (18.2%) of the 44 patients. During a median follow-up of 59 months, 3 (37.5%) of the 8 patients with EpCAM-positive DTCs relapsed, whereas none of the DTC-negative patients developed tumor recurrence (P=0.004). Survival analysis revealed a significant effect of the prevalence of DTCs on overall survival (P=0.0009) and on recurrence-free survival (P=0.0001). Finally, the prevalence of EpCAM-positive DTCs in perirectal LNs was significantly correlated with a high density of peritumoral lymphatic vessels (P=0.015). Our results show that DTCs may occur in stage I of rectal cancer and are associated with poor prognosis. Their occurrence seems to be linked to a high density of newly formed lymphatic vessel at the primary tumor site. According to our data, patients with DTCs in their LN might benefit from adjuvant therapy.
Department of General, Visceral, and Paediatric Surgery, University Hospital Dusseldorf, 40225 Düsseldorf, Germany.
Sameer
S
Dhayat
Sorina
S
Sorescu
Daniel
D
Vallböhmer
Sebastian
S
Kraus
Stephan Ernst
SE
Baldus
Alexander
A
Rehders
Feride
F
Kröpil
Andreas
A
Krieg
Wolfram Trudo
WT
Knoefel
Nikolas Hendrik
NH
Stoecklein
D000230:Adenocarcinoma / Q000276:immunology* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived; D000951:Antigens, Neoplasm / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D015815:Cell Adhesion Molecules / Q000032:analysis*; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D004729:Endothelium, Lymphatic / Q000276:immunology / Q000473:pathology; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012004:Rectal Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D012189:Retrospective Studies; D013997:Time Factors
D058846:Antibodies, Monoclonal, Murine-Derived; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; C500987:monoclonal antibody D2-40