Expression of Matrix Metalloproteinases in Supraglottic Carcinoma and Its Clinical Implication for Estimating Lymph Node Metastases

Objective: Twenty to 30% of clinically node-negative patients with squamous cell carcinoma (SCC) of supraglottic larynx were pathologically confirmed with occult lymph node metastasis after operation. Therefore, preoperative judgment on the neck node metastasis should be very important for making an appropriate surgical plan. The purpose of this study is to explore the role of matrix metalloprotineases (MMPs) in the metastatic potential of supraglottic carcinoma in this regard.

Study Design: Examination of MMPs expression in supraglottic carcinoma and establishment of the mathematic model for diagnosis of occult lymph node metastases in a prospective manner.

Methods: Thirty-two patients with supraglottic SCC underwent supraglottic horizontal partial laryngectomy and neck dissection, and the samples of primary cancer and the corresponding adjacent non-neoplastic tissues were evaluated for both mRNA and protein expression of MMP-1, MMP-2, MMP-7, MMP-8, MMP-9, and MMP-10 using reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. In addition, cervical lymph nodes were examined by routine histopathology to determine whether there was any evidences of node metastasis. RT-PCR and immunohistochemical data were analyzed by multivariate logistic regression, and then two mathematical models were established according to the multivariate logistic regression analysis.

Results: Among the six kinds of MMPs, both mRNA and protein expression of MMP-2, MMP-7, and MMP-9 were found up-regulated in more than 63% of the tumor tissues as compared with the adjacent non-neoplastic tissues, and this was significantly correlated with lymph node metastasis (all P < .05). Twenty patients, including seven cases with N0, were pathologically confirmed as having cervical lymph node metastasis. Using RT-PCR and immunohistochemical data of MMP-2, MMP-7, and MMP-9, two mathematic models were tested, and their diagnostic efficiencies for lymph node metastasis were 84% and 88%, respectively.

Conclusion: Expressions of MMP-2, MMP-7, and MMP-9 are up-regulated in supraglottic carcinoma tissues, suggesting that MMPs may be useful in the detection of occult lymph node metastasis but that more research is needed.