Are disseminated tumor cells in bone marrow and tumor-stroma ratio clinically applicable for patients undergoing surgical resection of primary colorectal cancer? The Leiden MRD study.
OBJECTIVE
Current TNM staging does not appropriately identify high-risk colorectal cancer (CRC) patients. The aim of this study was to evaluate whether the presence of disseminated tumor cells (DTCs) in the bone marrow (BM) and the presence of stroma in the primary tumor, i.e., the tumor-stroma ratio (TSR), in patients undergoing surgical resection of primary CRC provides information relevant for disease outcome.


METHODS
Patients with primary CRC (n = 125), consecutively admitted for curative resection between 2001 and 2007, were included in the study. All patients underwent BM aspiration before surgery. Detection of tumor cells was performed using immunocytochemical staining for cytokeratin (CK-ICC). The TSR was determined on diagnostic H&E stained sections of primary tumors.


RESULTS
DTCs were detected in the BM of 23/125 patients (18 %). No association was found between BM status and overall survival (HR 0.97 (95 % CI 0.45-2.09), p = 0.93). Also, no significant difference was found in their 5-year survival rate (resp. 72 % and 68 % for BM-positive versus BM-negative patients). The TSR was found to be associated with a worse overall survival (HR 2.16, 95 % CI 1.02-4.57, p = 0.04) with 5-year survival rates of 84 % versus 62 % for stroma-low and stroma-high patients, respectively. No relation was found between the presence of DTCs and TSR.


CONCLUSIONS
Our data indicate that the presence of DTCs in the BM of CRC patients is not associated with disease outcome. The TSR was, however, found to be associated with a worse overall survival, which indicates that for CRC the tumor microenvironment plays an important role in its behavior and prognosis.
Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.|Department of Surgery, VieCuri Medical Center, Venlo, The Netherlands.
F J
FJ
Vogelaar
Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
G W
GW
van Pelt
Department of Pathology, Antonius Hospital, Nieuwegein, The Netherlands.
A M
AM
van Leeuwen
Department of Geriatrics and Gerontology, Leiden University Medical Center, Leiden, The Netherlands.
J M
JM
Willems
Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
R A E M
RA
Tollenaar
Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
G J
GJ
Liefers
Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. W.E.Mesker@lumc.nl.
W E
WE
Mesker
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005109:Extracellular Matrix / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D059016:Tumor Microenvironment
Colon cancer; Disseminated tumor cells; Tumor microenvironment; Tumor-stroma ratio