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The presence of lymph node metastasis is the most important prognostic factor in oral cancer. The purpose of this study was to find useful markers for predicting occult cervical lymph node metastasis in patients with stage I or II squamous cell carcinoma of the oral cavity. We investigated 6 clinicopathologic factors and 2 genetic markers to predict late or occult cervical metastasis in 33 patients with stage I and II oral squamous cell carcinoma who underwent partial glossectomy through the mouth without elective neck dissection. In this study, we performed fluorescence in situ hybridization (FISH) with specimens obtained by fine-needle aspiration biopsies (FNA biopsies) of primary oral cancer material, to investigate numerical aberration of the gene. Late cervical lymph node metastasis occurred in 16 of the 33 patients (48.5%) during follow-up after treatment of the primary tumor. Factors significantly associated with the development of cervical metastasis were the mode of invasion (p = 0.009), cyclin D1 (p = 0.003) and EGFR numerical aberration (p = 0.024). The rate of disease-free survival from metastatic disease was significantly lower in patients with mode of invasion 4 C-4 D than in those with 1-3, and was significantly lower in patients with cyclin D 1 or EGFR gene numerical aberrations than in those without such aberrations (log rank test, p = 0.0064, p = 0.0016 or p = 0.0150). Our results indicate that patients with stage I - II squamous cell carcinoma of the oral cavity with the mode of invasion 4 C or 4 D, cyclin D 1 and EGFR gene numerical aberration should be considered a high-risk group for late cervical lymph node metastasis.

Prediction of Occult Cervical Lymph Node Metastasis in Patients with Stage I-II Squamous Cell Carcinoma of the Oral Cavity