Clinicopathological Evaluation of Late Cervical Lymph Node Metastatsis of Oral Squamous Cell Carcinoma
Control of the cervical lymph node metastasis (CLNM) is one of the important factors in improving the treatment outcome of oral squamous cell carcinoma (OSCC). Late CLNM shows poor prognosis, despite controlling the primary tumor. In order to predict indicators for late CLNM, we evaluated clinicopathological factor of late CLNM in N0 cases of OSCC. We also examined the expression of aldehyde dehydrogenase (ALDH) 1 and ATP-binding cassette G2 subfamily (ABCG) 2 which could be cancer stem cell markers of the oral tumor, and ascertain whether they might be a predictive marker of the late CLNM or not.
2. Materials and methods
The medical records of 105 consecutive patients who underwent primary surgery for OSCC from April 2007 to March 2013 at the Department of Oral Surgery, Tokushima University Hospital, were reviewed retrospectively. The criteria for enrollment were as follows; (1) patients had not previously been treated for OSCC, (2) patients was confirmed by a biopsy to be SCC, (3) lymph node metastases were not found, and (4) primary tumor was completely resected. Patients with the following criteria were excluded; (1) patients treated for recurrent tumor, or (2) patients with distant metastasis at the time of initial treatment. Moreover, we examined the expression of ALDH1 and ABCG2 by immunohistochemistry staining. Tissue specimens of the primary site were obtained from patients with OSCC after surgery or biopsy.
3. Methods of data analysis
The relationship of categorical variables was analyzed by Mann-Whitney’s U test. Overall survival was determined using the Kaplan-Meier method. A P value <0.05 was considered statistically significant.
Immunohistochemistry was used to assess ALDH1 and ABCG2 protein using at least 10% staining-positive cells as the definition of positive staining.
4. Results
Fourteen of the 105 patients (13.3%) who were able to control a primary tumor showed late CLNM. The primary site with the most frequent incidence of late CLNM was the buccal mucosa (27.3%), mandibular gingiva (14.8%), maxillary gingiva (14.3%), floor of mouth (12.5%) and tongue (8.9%). The period until the late CLNM appeared after surgery was from two months to three years and five months, and the median period was six months. There was significant association between incidence of late CLNM and histological differentiation or invasion mode (YK classification). According to the YK classification, the rate of late CLNM was 0% at YK1, 6.9% at YK2, 16.7% at YK3, 9.1% at YK4C, and 66.7% at YK-4D. The control rate of late CLNM was 85.7%. There was a significant difference between three years overall survival rate and the patients with/without incidence of late CLMN.
ALDH1 expression of late CLNM patients was higher than those of non-late CLNM. Whereas，ABCG2 expression of late CLNM patients was significantly higher than those of non-late CLNM.
5. Conclusions
These findings suggested that the patients with incidence of late CLNM showed poor prognosis, and incidence of late CLNM could be related to histological differentiation and invasion mode. The expression of ABCG2 might be a marker of late CLNM.
6. References
1) Umeda, M., Yokoo, S. et al: Lymph node metastasis in squamous cell carcinoma of the oral cavity: correlation between histlogic features and the prevalence of metastasis. Head and Neck 14: 263-272 1992.
2) Yamamoto, E., Kohama, G. et al: Mode of invasion, bleomycin sensitivity and clinical course in squamous cell carcinoma of the oral cavity. Cancer 51: 2175- 2180 1983.