Malignant melanoma: relationship of the human leukocyte antigen class II gene DQB1*0301 to disease recurrence in American Joint Committee on Cancer Stage I or II.

Abstract

Melanoma patients who carry the human leukocyte antigen (HLA) Class II allele DQB1*0301 have an increased frequency of metastases at presentation compared with those lacking HLA-DQB1*0301. This study was designed to determine whether HLA-DQB1*0301 is associated with an increased risk of recurrence in melanoma patients presenting with American Joint Committee on Cancer (AJCC) Stage I or II (localized) disease. Molecular oligotyping of HLA-DQ genes was performed for 259 patients with AJCC Stage I or II melanoma. Rate of disease recurrence was determined by retrospective review and prospective follow-up. Kaplan-Meier analysis, log rank, and proportional hazard (Cox) comparison were performed. Median follow-up was 24 months. Minimum follow-up was 6 months. Although HLA-DQB1*0301-positive and -negative patients were balanced with regard to standard melanoma prognostic factors (primary tumor thickness, level of invasion, presence of ulceration, anatomic location, and sex), HLA-DQB1*0301-positive patients were more likely to develop locally recurrent, regional, or distant metastatic melanoma during follow-up (actuarial median disease free survival 48 months [DQB1*0301-positive patients] vs. 97 months [DQB1*0301-negative patients]; log rank P = 0.0002). HLA-DQB1*0301 status, in addition to primary tumor thickness, was an independent prognostic indicator in these patients (Cox multivariate P = 0.02). Patients presenting with localized melanoma who carry HLA-DQB1*0301 are at an increased risk of developing recurrent disease compared with stage-matched patients who lack this allele. HLA-DQB1*0301 is a genomic marker which independently identifies melanoma patients in whom recurrence is more likely, and is potentially useful in selecting those most likely to benefit from adjuvant therapy.