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A. Iovieno, A. Micera, B. Stampachiacchiere, C. Moretti, E. Perrella, S. Bonini; Characterization of MMP-2/MMP-9 and TIMP-1 Expression and Activity in Conjunctival Squamous Cell Carcinoma at Baseline and During 5-Fluorouracil Topical Chemotherapy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5016.
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The aim of this study was to evaluate the effect of 5-fluorouracil (5-FU) topical treatment on tear MMP-2/MMP-9/TIMP-1 expression and activity in a patient affected by conjunctival Squamous Cell Carcinoma (SCC).
A 71-year-old male patient was affected by SCC in his left eye. After surgical excision of the mass, a recurrence of the lesion was observed in the same area. The patient was then treated with topical 0.1% 5-FU 4 times a day, for 4 weeks. 5-FU treatment was successful in eradicating the clinical lesion in 4 weeks. Conjunctival biopsy was sampled from the unaffected eye for immunohistochemical evaluation, and compared to the previous excised tumor. Conjunctival impression cytology and tears were collected before and after 2 and 4 weeks from beginning of treatment, to evaluate MMP-2/MMP-9 and TIMP-1 expression and function by gelatine zymography and real-time PCR analysis. Impression cytology and tear sampling were also performed on an unaffected conjunctival area of the treated eye and from the healthy contralateral one.
Immunohistochemical analysis of the excised tumor showed an increase of MMP-2/MMP-9 proteins in SCC, mainly localized in the epithelium, as compared to the healthy conjunctiva. At baseline, conjunctival epithelium from SCC showed an increase of MMP-2/MMP-9 and TIMP-1 mRNA expression, compared to healthy conjunctiva from the same eye (1.5, 3, 3 fold-increase, respectively) and from the controlateral eye (2.4, 1.2, 2.8 fold-increase, respectively). In parallel, zymography showed higher gelatinolytic activity of MMP-2/MMP-9 in tears from the affected eye. A progressive and significant reduction of MMP-2/MMP-9 and TIMP-1 mRNA expression was observed in SCC epithelium after two (3.6, 2.1, 2 fold-decrease, respectively) and four (12, 9.2, 4.2 fold-decrease respectively) weeks of topical 5-FU chemotherapy. Zymography showed that MMP-2/MMP-9 gelatinolytic activity was similar in both eyes.
This case report indicates that MMP-2/MMP-9 and TIMP-1 expression are affected in an ocular surface neoplasm, and that 5-FU-therapy is able to counteract this increase (expression/activity). These findings indicate that changes of MMP-2/MMP-9 and TIMP1 expression might be correlated with the neoplasm’s response to chemotherapy.
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