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.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Lee
J E
JE
Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Lu
M
M
Mansfield
P F
PF
Platsoucas
C D
CD
Reveille
J D
JD
Ross
M I
MI
D000483:Alleles; D005260:Female; D005500:Follow-Up Studies; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen