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Changes in the expression of MMP2, MMP9, and ColIV in stromal cells in oral squamous tongue cell carcinoma: relationships and prognostic implications

Hai-Xia Fan1, Hai-Xia Li1, Dong Chen2, Zhong-Xiuzi Gao1 and Jin-Hua Zheng1,3,4*

Author Affiliations

1 Department of Anatomy, Basic Medical Science College, Harbin Medical University, Harbin, China

2 Harbin Medical University Stomatological Hospital, Harbin Medical University, Harbin, Heilongjiang, China

3 Department of Physics and Laboratory of Sono- and Photo-theragnostic Technologies, Harbin Institute of Technology, Harbin, China

4 Department of Anatomy, Basic Medical Science College of Harbin Medical University, 194 Xuefu-Road, Harbin 150081, China

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Journal of Experimental & Clinical Cancer Research 2012, 31:90 doi:10.1186/1756-9966-31-90

Published: 29 October 2012

Abstract

Background

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.

Methods

Here, 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.

Results

MMP-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.

Conclusions

Degradation 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.

Keywords:
Oral tongue squamous carcinoma; MMPs; ColIV; Immunohistochemistry; Prognosis