Evaluation of SHP1-P2 methylation as a biomarker of lymph node metastasis in patients with squamous cell carcinoma of the head and neck

Background: Hypermethylation of Src homology region 2 domain-containing protein-tyrosine phosphatase 1 promoter 2 (SHP1-P2) has been proven as an epithelial-specific marker. This marker has been used for the detection of lymph node metastasis in patients with lung cancer or colon cancer. Objectives: To investigate SHP1-P2 methylation in patients with squamous cell carcinoma of the head and neck (HNSCC) and determine its potential for micrometastasis detection in the lymph nodes of patients with HNSCC. Methods: SHP1-P2 methylation levels were analyzed by combined methylation-specific primer TaqMan real-time PCR in 5 sample groups: normal tonsils (n = 10), microdissected squamous cell carcinoma epithelia (n = 9), nonmetastatic head and neck cancer lymph nodes (LN N0, n = 15), metastatic HNSCC histologically negative for tumor cells (LN-, n = 18), and matched cases histologically positive for tumor cells (LN+, n = 18). Results: SHP1-P2 methylation of 10.27 +/- 4.05% was found in normal tonsils as a lymphoid tissue baseline, whereas it was 61.31 +/- 17.00% in microdissected cancer cell controls. In the 3 lymph node groups, the SHP 1-P2 methylation levels were 9.99 +/- 6.61% for LN NO, 14.49 +/- 10.03% for LN- Nx, and 41.01 +/- 24.51% for LN+ Nx. The methylation levels for LN- Nx and LN+ Nx were significantly different (P = 0.0002). Receiver operating characteristic curve analysis of SHP1-P2 methylation demonstrated an area under the curve of 0.637 in distinguishing LN NO from LN-Nx. Conclusions: SHP1-P2 methylation was high in HNSCC, and low in lymphoid tissues. This methylation difference is concordant with lymph node metastasis.