Direct genetic analysis of single disseminated cancer cells for prediction of outcome and therapy selection in esophageal cancer.
The increasing use of primary tumors as surrogate markers for prognosis and therapeutic decisions neglects evolutionary aspects of cancer progression. To address this problem, we studied the precursor cells of metastases directly for the identification of prognostic and therapeutic markers and prospectively analyzed single disseminated cancer cells from lymph nodes and bone marrow of 107 consecutive esophageal cancer patients. Whole-genome screening revealed that primary tumors and lymphatically and hematogenously disseminated cancer cells diverged for most genetic aberrations. However, we identified chromosome 17q12-21, the region comprising HER2, as the most frequent gain in disseminated tumor cells that were isolated from both ectopic sites. Survival analysis demonstrated that HER2 gain in a single disseminated tumor cell but not in primary tumors conferred high risk for early death.
Stoecklein
Nikolas H
NH
Department of Pathology, Division of Oncogenomics, University of Regensburg, D-93053 Regensburg, Germany.
Hosch
Stefan B
SB
Bezler
Martin
M
Stern
Franziska
F
Hartmann
Claudia H
CH
Vay
Christian
C
Siegmund
Annika
A
Scheunemann
Peter
P
Schurr
Paulus
P
Knoefel
Wolfram T
WT
Verde
Pablo E
PE
Reichelt
Uta
U
Erbersdobler
Andreas
A
Grau
Roger
R
Ullrich
Axel
A
Izbicki
Jakob R
JR
Klein
Christoph A
CA
D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D018734:Genes, erbB-2; D015894:Genome, Human; D006801:Humans; D008207:Lymphatic Metastasis; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016896:Treatment Outcome