Prognostic significance of cytokeratin-20 reverse transcriptase polymerase chain reaction in lymph nodes of node-negative colorectal cancer patients.
OBJECTIVE
Approximately 20% to 30% of patients with curatively resected, node-negative (pN0) colorectal cancer die of tumor recurrence, which can be caused by minimal residual disease. To identify patients with an increased risk of tumor recurrence and evaluate the prognostic value of cytokeratin-20 (CK-20), we detected CK-20-positive cells in histopathologically tumor-free lymph nodes (pN0) of patients with colorectal cancer.


METHODS
Two peritumoral lymph nodes each from 85 patients with completely resected (R0) colorectal cancer without lymph node metastases (pN0) by routine examination were analyzed using a CK-20-specific reverse transcriptase polymerase chain reaction (RT-PCR) and compared with CK-20-specific immunohistochemistry (IHC). The results were correlated with histopathologic findings and with survival.


RESULTS
CK-20 RT-PCR was positive in 44 patients (52%) and detected 83% of cancer-related death. Positive RT-PCR was significantly correlated with poorer overall survival (P <.009). Comparing RT-PCR with IHC, 13 patients with positive RT-PCR were identified, where the CK-20 expression was caused by tumor cell contamination located exclusively outside the lymph node capsule and had no prognostic impact. Defining these 13 patients as RT-PCR negative improved specificity of the RT-PCR assay from 57% to 75%. The 5-year overall survival of the 31 RT-PCR-positive patients was 71%, compared with 96% in the 54 negative patients (P <.001). Multivariate analysis showed expression of CK-20 mRNA to be an independent prognostic factor with a relative risk of cancer-related death of 6.1.


CONCLUSIONS
CK-20 RT-PCR in peritumoral histopathologic tumor-free (pN0) lymph nodes of colorectal cancer is an independent prognostic factor for overall survival. Additional CK-20 IHC improves the specificity and prognostic value of RT-PCR for cancer-related death.
Rosenberg
Robert
R
Chirurgische Klinik und Poliklinik and Institut für Pathologie und Pathologische Anatomie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Hoos
Axel
A
Mueller
James
J
Baier
Patricia
P
Stricker
Dominik
D
Werner
Martin
M
Nekarda
Hjalmar
H
Siewert
Jörg-Rüdiger
JR
D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000096:biosynthesis*; D053554:Keratin-20; D008198:Lymph Nodes; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D016019:Survival Analysis
D004273:DNA, Neoplasm; D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; D053554:Keratin-20; D012333:RNA, Messenger