0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Expression of HLA Class I Antigen, Aspirin Use, and Survival After a Diagnosis of Colon Cancer

Marlies S. Reimers, MD1; Esther Bastiaannet, PhD1,2; Ruth E. Langley, MD3; Ronald van Eijk, PhD4; Ronald L. P. van Vlierberghe, BSc1; Valery E. P. Lemmens, PhD5; Myrthe P. P. van Herk-Sukel, PhD6; Tom van Wezel, PhD4; Riccardo Fodde, PhD7; Peter J. K. Kuppen, PhD1; Hans Morreau, MD4; Cornelis J. H. van de Velde, MD1; Gerrit Jan Liefers, MD1
[+] Author Affiliations
1Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
2Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
3Medical Research Council Clinical Trials Unit, University College, London, England
4Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands
5Comprehensive Cancer Centre South, Eindhoven Cancer Registry, Eindhoven, the Netherlands
6PHARMO Institute for Drug Outcomes Research, Utrecht, the Netherlands
7Department of Experimental Pathology, Erasmus University Medical Center, Rotterdam, the Netherlands
JAMA Intern Med. 2014;174(5):732-739. doi:10.1001/jamainternmed.2014.511.
Text Size: A A A
Published online

Importance  Use of aspirin (which inhibits platelet function) after a colon cancer diagnosis is associated with improved overall survival. Identifying predictive biomarkers of this effect could individualize therapy and decrease toxic effects.

Objective  To demonstrate that survival benefit associated with low-dose aspirin use after a diagnosis of colorectal cancer might depend on HLA class I antigen expression.

Design, Setting, and Participants  A cohort study with tumor blocks from 999 patients with colon cancer (surgically resected between 2002 and 2008), analyzed for HLA class I antigen and prostaglandin endoperoxide synthase 2 (PTGS2) expression using a tissue microarray. Mutation analysis of PIK3CA was also performed. Data on aspirin use after diagnosis were obtained from a prescription database. Parametric survival models with exponential (Poisson) distribution were used to model the survival.

Main Outcomes and Measures  Overall survival.

Results  The overall survival benefit associated with aspirin use after a diagnosis of colon cancer had an adjusted rate ratio (RR) of 0.53 (95% CI, 0.38-0.74; P < .001) when tumors expressed HLA class I antigen compared with an RR of 1.03 (0.66-1.61; P = .91) when HLA antigen expression was lost. The benefit of aspirin was similar for tumors with strong PTGS2 expression (0.68; 0.48-0.97; P = .03), weak PTGS2 expression (0.59; 0.38-0.97; P = .02), and wild-type PIK3CA tumors (0.55; 0.40-0.75; P < .001). No association was observed with mutated PIK3CA tumors (0.73; 0.33-1.63; P = .44).

Conclusions and Relevance  Contrary to the original hypothesis, aspirin use after colon cancer diagnosis was associated with improved survival if tumors expressed HLA class I antigen. Increased PTGS2 expression or the presence of mutated PIK3CA did not predict benefit from aspirin. HLA class I antigen might serve as a predictive biomarker for adjuvant aspirin therapy in colon cancer.

Figures in this Article

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Figures

Place holder to copy figure label and caption
Figure 1.
Representative Images of Immunohistochemical Staining for HLA Class I Antigen Expression (HCA2 and HC10) and Prostaglandin Endoperoxide Synthase 2 (PTGS2)

Staining performed according to standard protocols, as detailed in the Methods section. A, HC10-negative tumor. B, HC10-positive tumor. C, HCA2-negative tumor. D, HCA2-positive tumor. E, Tumor with weak PTGS2 expression. F, Tumor with strong PTGS2 expression. G, Enlarged view of sample in F. See the Tissue Microarray Production and Immunohistochemistry subsection of the Methods section for details of the immunohistochemical staining methods used. Original magnifications ×20 (A-F) and ×40 (G).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Curves for Overall Survival in Patients With Colon Cancer According to Aspirin Use After Diagnosis or Nonuse of Aspirin After Diagnosis and HLA Class I Antigen Expression

A, Overall survival among patients with loss of HLA class I antigen in tumor sections. B, Overall survival among patients with expression of HLA class I antigen in tumor sections.

Graphic Jump Location

Tables

References

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 3

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles
Jobs
JAMAevidence.com

Users' Guides to the Medical Literature
Clinical Resolution

Users' Guides to the Medical Literature
Clinical Resolution

brightcove.createExperiences();