Annals of Surgical Oncology

, Volume 25, Issue 5, pp 1374–1380 | Cite as

The Negative Impact of Body Mass Index on the Tumor Microenvironment in Colon Cancer: Results of a Prospective Trial

  • Devin C. Flaherty
  • John R. Jalas
  • Myung S. Sim
  • Alexander Stojadinovic
  • Mladjan Protic
  • Delphine J. Lee
  • Anton J. Bilchik
Colorectal Cancer

Abstract

Background

The association between tumor mismatch repair status and obesity in colon cancer is not well understood. The authors of this study hypothesized that mismatch repair deficiency in colon cancer may be associated with a lower Body Mass Index (BMI) and improved patient outcome due to an enhanced tumor immune microenvironment.

Methods

For this study, 70 patients were randomly selected from a prospective trial evaluating nodal ultrastaging for colon cancer. The mismatch repair status of tumors and immunomarker expression were correlated with clinicopathologic characteristics and evaluated for disease-free survival.

Results

Patients with mismatch repair-deficient tumors (n = 11) had a lower mean BMI than those with mismatch repair-proficient tumors (n = 59) (22.16 vs. 26.30 kg/m2, respectively; p = 0.029).The findings showed that CD3+ T cells were inversely associated with mismatch repair proficiency (p = 0.048). Mismatch repair-proficient tumors in nonobese patients (BMI < 30 kg/m2) versus obese patients had a higher density of CD8+ (p = 0.008) and FOXP3+ (p = 0.005) T cells. Multivariable analysis linked CD4+ (hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.35–0.76), CD8+ (HR 0.67; 95% CI 0.50–0.89), and number of tumor-positive lymph nodes (HR 1.19; 95% CI 1.03–1.36) to disease-free survival for patients with mismatch repair-proficient tumors.

Conclusions

Tumor mismatch repair status and obesity are correlated in patients with colon cancer. Increased intratumoral T cells in nonobese patients suggests an unexplored link between tumor mismatch repair and immunoprofile.

Notes

Acknowledgment

Financial support for the NYULMC Experimental Pathology Immunohistochemistry Core Laboratory and Clarient Diagnostic Services was provided in part by the Laura and Isaac Perlmutter Cancer Center Support grant NIH/NCI P30CA016087 and the National Institutes of Health Shared Instrumentation (S10) Grants NIC/ORIP S10OD0D10584-01A1 and S10ODOD10584-01A1. Author D.C.F is currently with Valley Health Surgical Oncology, Winchester, VA. Author D.J.L. is currently the Director of the Dermatological Center for Skin Health at Providence Saint John’s Health Center and the Division Chief Dermatology and Residency Program Director at Harbor-UCLA Medical Center, Torrance, California. This project was support by funds from the National Cancer Institute (RO1CA090848) and the California Oncology Research Institute. The authors take sole responsibility for the data reported, and the content within the manuscript in no way represents official views of the National Cancer Institute or the National Institutes of Health.

Supplementary material

10434_2018_6405_MOESM1_ESM.tif (2.4 mb)
Fig. S1 Magnified (×100) representative digital images of immunohistochemistry stains for the mismatch repair proteins MSH-2 (panels 1 & 5), MLH-1 (panels 2 & 6), PMS-2 (panels 3 & 7), and MSH-6 (panels 4 & 8) from two separate patients. Patient A is considered mismatch repair-proficient, whereas patient B is mismatch repair-deficient because panels 6 and 7 exhibit loss of staining of the proteins MLH-1 and PMS-2 (arrows). (TIFF 2441 kb)

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Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Devin C. Flaherty
    • 1
  • John R. Jalas
    • 2
  • Myung S. Sim
    • 3
  • Alexander Stojadinovic
    • 4
  • Mladjan Protic
    • 5
    • 6
  • Delphine J. Lee
    • 7
  • Anton J. Bilchik
    • 1
    • 8
  1. 1.Department of Surgical OncologyJohn Wayne Cancer Institute at Providence Saint John’s Health CenterSanta MonicaUSA
  2. 2.Department of PathologyProvidence Saint John’s Health CenterSanta MonicaUSA
  3. 3.Department of MedicineDavid Geffen School of Medicine at UCLALos AngelesUSA
  4. 4.Uniformed Services University of the Health SciencesBethesdaUSA
  5. 5.Clinic of Surgical OncologyOncology Institute of VojvodinaSremska KamenicaSerbia
  6. 6.Faculty of MedicineThe University of Novi SadNovi SadSerbia
  7. 7.Dirks/Dougherty Laboratory for Cancer Research, Department of Translational ImmunologyJohn Wayne Cancer Institute at Providence Saint John’s Health CenterSanta MonicaUSA
  8. 8.California Oncology Research InstituteLos AngelesUSA

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