BACKGROUND: Laryngeal cancer can cause hoarse voice, dyspnea, and dysphagia, for which common surgical approaches or biotherapy hardly results when nodal metastases are present. Identification of the factors associated with laryngeal cancer metastases is a crucial task in the study of the malignancy, as such a revelation may help establish molecular markers for accurate assessment of metastases and develop biological agents to restrain the invasion and metastases.OBJECTIVE:To study the association of MMP-2, MMP-9, CD44v6, PCNA,nm23, VEGF, p53, Cath-D and E-cadherin with the metastasis of laryngeal cancer so as to provide evidence for clinical treatment of laryngeal cancer.DESIGN: An experimental study ofclinical specimens.PARTICIPANTS: All specimens of primary laryngeal cancer were obtained from patients receiving surgical treatment in the Department of Otolaryngology,Fourth Affiliated Hospital of Harbin Medical University from February 2002 to November 2003. Immunohistochemical examination of the specimens was conducted in the Third Affiliated Hospital of Sun Yat-sen University.INTERVENTIONS: The expressions of MMP-2, MMP-9, CD44v6, PCNA,nm23, VEGF, p53, Cath-D and E-cadherin were examined immunohistochemically in the specimens from 70 patients of laryngeal cancer. Logistic stepwise regression model was used to analyze the influence of the 9 clinicopathologic factors on lymph node metastasis.MAIN OUTCOME MEASURES: The expressions of MMP-2, MMP-9,CD44v6, PCNA, nm23, VEGF, p53, Cath-D and E-cadherin in laryngeal cancer specimens.RESULTS: Using the established equation to estimate lymph node metastasis, the frequency of lymph node metastasis was highest in patients with positive MMP-9 expression(Wald = 10. 350 1, P ＜ 0.05) . Lower E-cadherin expression was accompanied by higher frequency of lymph node metastasis, and nm23 expression in patients with lymph node metastases was significantly decreased in comparison with patients without metastases (Wald=6.189 6 and 6. 863 2, P ＜0.05).CONCLUSION: The expressions of MMP-9, E-cadherin and nm23 are useful indicators for preoperative prediction of lymph node metastasis of laryngeal cancer and provide valuable information for prognostic evaluation of the interventions.

BACKGROUND: Matrix metalloproteinases-7 (MMP-7) plays an important role in the invasion and metastasis of cancer and is related to prognosis of many carcinomas.OBJECTIVE: To investigate the significance of MMP-7 expression in the invasion and metastasis of laryngeal cancer and explore the relationship between MMP-7 expression and the prognosis of laryngeal squamous cell cancer (LSCC).DEGIGN: An open experimental study based on the cells.SETTING: Two otolaryngology departments of two university hospitals and one otolaryngology department of a municipal hospital.MATERIALS: The experiment was conducted in the Center Laboratory of Second Affiliated Hospital of Harbin Medical University from April 2002 to January 2003. The materials were laryngeal cancer and corresponding neighboring noncancerous tissues, MMP-7 antibody and immunohistochemical kit.METHODS: The expression of MMP-7 protein in 70 samples of paraffin-embedded LSCC and corresponding neighboring noncancerous tissues was detected with immunohistochemical technique. Reverse transcription-polymerase chain reaction(RT-PCR) and Western blot technique were used to examine the expression of MMP-7 in 35 frozen specimens of LSCC and corresponding neighboring noncancerous tissues.MAIN OUTCOME MEASURES: The relationship of MMP-7 mRNA expression with the invasion depth(T grade), neck nodal metastasis and prognosis of LSCC.RESULTS: Immunohistochemical staining of MMP-7 was observed in 77.1% (54/70) of cancer tissues and in 5.7% (4/70) of neighboring noncancerous tissues( P ＜ 0.01) . The mRNA expression of MMP-7 was detected in 74.3% (24/35) of cancer tissues and in 5.7% (2/35) of neighboring noncancerous tissues( P ＜ 0.01 ). The expression of MMP-7 was higher in T3-T4 group than that in T1-T2 group(P ＜ 0.01), and was positively correlated with nodal metastasis( P ＜ 0. 01 ). Western blot showed that both 28 ku (latent form of MMP-7) and 19 ku(active form of MMP-7)bands had close relationship with T grade and neck nodal metastasis. Kaplan-Meier survival curve showed that the group with high MMP-7protein expression had poorer prognosis than the group with weak or negative MMP-7 protein expression(Log-rank = 4. 755 9, 8. 951 3; P = 0. 029 2,0.002 8).CONCLUSION: MMP-7 is closely correlated with the invasion, metastasis,and prognosis of LSCC, and it may serve as a marker in estimating the invasive and metastatic potency and prognosis of LSCC.