Abstract
BackgroundType IV collagen (ColIV) is the most important scaffold for the basement membrane (BM) proteins, and plays an important role in regulating and limiting tumour invasion and metastasis.MethodsHere, we observed the changes in morphology and distribution of type IV collagen (ColIV) in the basement membrane (BM) surrounding nests of carcinoma in 48 patients with oral tongue squamous cell (OTSCC). We examined the correlation between the expressions of ColIV, MMP-2 and MMP-9 and the prognosis of OTSCC patients. The intensity and patterns of expression were assessed immunohistochemically using anti-human mouse monoclonal MMP-2, MMP-9 and Col IV antibodies. Statistical analyses were performed to determine the prognostic correlations of ColIV, MMP-2, and MMP-9 levels.ResultsMMP-2 and MMP-9 expressions in OTSCC were higher than those in normal oral mucosa and dysplastic oral mucosa group(MMP-2 iOD: 66.40 ± 24.20, 134.69 ± 37.08, and 357.79 ± 116.78; MMP-9 iOD: 88.05 ± 23.85, 307.13 ± 93.22, and 791.31 ± 260.52; in normal, dysplastic oral mucosa, and tumour tissues, respectively, P < 0.01); however, ColIV immunoreactivity was lower (ColIV iOD: 406.87 ± 62.95, 247.83 ± 42.30, and 151.92 ± 38.17 in normal, dysplastic oral mucosa, and tumour tissues, respectively, P < 0.01). High tumour and stromal MMP-2 and MMP-9 expression was significantly associated with positive lymph node status. Col IV expression was associated with positive lymph node status (P < 0.05), and have negatively correlated with the expression of MMP-2 and MMP-9. Overall survival was significantly shorter in patients with high tumour and stromal MMP-2 and MMP-9 expression, and tended to be shorter in patients with low ColIV expression.ConclusionsDegradation of ColIV was closely related to increased MMP-2 and MMP-9 expression; MMP-9 have more important function than MMP-2 during the cancer development. Monitoring changes in the expression of ColIV, MMP-2, and MMP-9 may be a useful technique for assessing prognoses in OTSCC patients.
Highlights
Type IV collagen (ColIV) is the most important scaffold for the basement membrane (BM) proteins, and plays an important role in regulating and limiting tumour invasion and metastasis
We aimed to investigate the expression of matrix metalloproteinase (MMP)-2, MMP-9 and ColIV, and the changes in the morphology of ColIV during tongue cancer development and their relationship with the stage and differentiation of Oral tongue squamous cell carcinoma (OTSCC) in order to determine if these results can be used to assess the prognosis in OTSCC patients
The expression of MMP-2, MMP-9 and ColIV in normal oral mucosa group Positive expression of MMP-2 and MMP-9 was mainly observed in the cytoplasm of stromal cells and proliferating epithelial cells as brownish granules under 400×
Summary
Type IV collagen (ColIV) is the most important scaffold for the basement membrane (BM) proteins, and plays an important role in regulating and limiting tumour invasion and metastasis. Infiltration is a prerequisite and key step of cancer metastasis; and is an important factor in the prognosis of patients with oral cancer. A key step in OTSCC infiltration and metastasis is the degradation of the basement membrane (BM) between the epithelium and lamina propria, around cancer nests, and surrounding vascular structures [3,4,5]. Tongue squamous cell carcinoma is prone to infiltration, during which ColIV in and around epithelial, vascular and tumour BM is often damaged, compromising its ability to limit the tumour invasion and metastasis [7,8,9]
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