High intratumoral FOXP3⁺ T regulatory cell (Tregs) density is an independent good prognosticator in nodal negative colorectal cancer.
Immunologic profiling of colorectal cancer (CRC) may help to predict the tumors metastatic potential and patients with an aggressive tumor, although not yet metastasized at time of surgery might benefit from adjuvant therapy. In this study we evaluated the prognostic significance of FOXP3(+) T regulatory cells (Tregs), CD3(+) and CD8(+) lymphocyte densities and conventional histopathologic features in nodal negative (n = 820, UICC stage II) CRC. Immunohistochemical studies showed that high expression of FOXP3(+) Tregs is significantly linked to a better clinical outcome (P = 0.0001). In multivariate analysis including tumor stage, tumor grade, type of tumor invasion margin (pushing vs. infiltrating type), lymphovascular invasion (absent vs. present), CD3(+), CD8(+) and FOXP3(+) Tregs expression, only low tumor stage, absence of lymphovascular invasion and high Foxp3 Tregs density showed prognostic significance (P = 0.0132, P = 0.0022 AND P = 0.0234, respectively). Our findings argue towards a clinical utility of FOXP3(+) Tregs immunostaining as an independent good prognostic biomarker in stage II colorectal cancers. FOXP3(+) Tregs immunoscoring, assessment of tumor stage and lymphovascular invasion may help to define stage II cancers with a potentially aggressive behavior and CRC patients who might benefit from adjuvant therapy. A two-scale immunosore related to the median count of FOXP3(+) Tregs proved to be easy and quick to perform.
Center for Dental and Oral Medicine, University Medical Center Hamburg-Eppendorf Hamburg 20246, Germany.
Tim
T
Hanke
Department of Surgery, University Medical Center Hamburg-Eppendorf Hamburg 20246, Germany.
Nathaniel
N
Melling
Institute of Pathology, University Medical Center Hamburg-Eppendorf Hamburg 20246, Germany.
Ronald
R
Simon
Institute of Pathology, University Medical Center Hamburg-Eppendorf Hamburg 20246, Germany.
Guido
G
Sauter
Department of Oncology, Hematology, BMT with Section Pneumology, Hubertus Wald Cancer Center, University Medical Center Hamburg-Eppendorf Hamburg 20246, Germany.
Carsten
C
Bokemeyer
Institute of Pathology, University Medical Center Hamburg-Eppendorf Hamburg 20246, Germany.
Patrick
P
Lebok
Institute of Pathology, University Hospital Basel Basel 4001, Switzerland.
Luigi M
LM
Terracciano
Department of Surgery, University Medical Center Hamburg-Eppendorf Hamburg 20246, Germany.
Jakob R
JR
Izbicki
Institute of Pathology, University Medical Center Hamburg-Eppendorf Hamburg 20246, Germany.
Andreas H
AH
Marx
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D005858:Germany; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D013557:Switzerland; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
Colorectal cancer; FOXP3+ Tregs; immunoscore; prognosis