Abstract
Purpose: :
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).
Methods: :
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.
Results: :
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.
Conclusions: :
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.
Keywords: tumors • conjunctiva • cytology