HLA Class I Antigen Expression Predicts Overall Survival Benefit With Aspirin Use in Colon Cancer
In a cohort study reported in JAMA Internal Medicine, Reimers et al found that aspirin use was associated with a significant 47% reduction in mortality risk after diagnosis of colon cancer expressing HLA class I antigen. There was no difference in aspirin benefit according to strong or weak prostaglandin endoperoxide synthase 2 (PTGS2) expression.
Study Details
Aspirin inhibits PTGS and platelet function. Platelets are believed to protect disseminating tumor cells from natural killer cells, which recognize and eliminate cells with low or no expression of HLA class I antigen. Thus, it was originally hypothesized that the survival benefit associated with low-dose aspirin use after colon cancer diagnosis would be most evident in tumors with low or no HLA class I antigen expression.
In the study, tumor blocks from 999 patients in the Eindhoven Cancer Registry who underwent surgical resection between 2002 and 2008 were analyzed for HLA class I antigen and PTGS2 expression using a tissue microarray, as well as for PIK3CA mutation status. Data on aspirin use after diagnosis were obtained from a prescription database in the Netherlands.
Overall Benefit of Aspirin Use
Of the 999 patients, 182 (18%) were aspirin users (given a prescription for aspirin for ≥ 14 days after colon cancer diagnosis) 817 were nonusers (never had a prescription for aspirin or had a prescription for < 14 days after diagnosis). The median duration of prescriptions was 30 days and the mean number of prescriptions was 12 (range, 1–220).
As of January 2012, there had been 465 deaths, including 396 deaths in aspirin nonusers (48.5%) and 69 deaths in aspirin users (38%) after diagnosis. Among the 999 patients, aspirin use after diagnosis was associated with significantly improved overall survival (rate ratio [RR] = 0.64, P = .001).
Characteristics of Aspirin Users
Of the 999 tumors, 36 could not be analyzed for HLA class I antigen expression due to staining artifacts or loss of material. Among the 963 patients with known HLA class I antigen status, 51% were male, 34%, 30%, and 35% were aged ≤ 65, 66 to 74, and ≥ 75 years, respectively; 14%, 40%, 29%, and 17% had stage I, II, III, and IV disease, respectively; 44% had comorbidity; and 87% had microsatellite stability.
A total of 643 patients (67%) had tumors expressing HLA antigen, including 122 aspirin users (19%), and 320 (33%) had HLA antigen loss, including 57 aspirin users (18%). Among patients with tumors expressing HLA class I antigen, aspirin users were significantly more likely to be male (64% vs 50%, P = .005), be older (eg, 19% vs 36% aged ≤ 65 years, P = .001 for trend), have lower-stage tumors (eg, 27% vs 14% stage I, 32% vs 40% stage II, P < .001 for trend), and to have comorbidity (79.5% vs 51%, P < .001). Among patients with HLA class I antigen loss, aspirin users were significantly more likely to be male and older and to have comorbidity.
Survival According to HLA Antigen, PTGS2, and PIK3CA Status
On multivariate analysis adjusting for sex, age, comorbidity, year of incidence, histologic grade, stage, and chemotherapy, aspirin use vs nonuse was associated with a 47% reduction in mortality among patients with HLA class I antigen expression (adjusted RR = 0.53, P < .001). There was no significant difference in mortality risk among patients with loss of HLA class I antigen expression (RR = 1.03, P = .91).
On multivariate analysis, aspirin use was associated with significantly lower mortality risk among patients with both low (RR = 0.59, P = .02) and high (RR = 0.68, P = .03) PTGS2 expression and among patients with wild-type (RR = .055, P < .001) but not mutated PIK3CA (RR = 0.73, P = .44).
The investigators concluded, “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.”
Gerrit Jan Liefers, MD, of Leiden University Medical Center, is the corresponding author for the JAMA Internal Medicine article.
The study was supported by a grant from the Sloos-Alandt family. For full disclosures of the study authors, visit archinte.jamanetwork.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
