May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
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
Author Affiliations & Notes
  • A. Iovieno
    University Campus Bio-medico, Rome, Italy
    Ophthalmology,
  • A. Micera
    University Campus Bio-medico, Rome, Italy
    Ophthalmology,
    Cir,
  • B. Stampachiacchiere
    University Campus Bio-medico, Rome, Italy
    Ophthalmology,
    Cir,
  • C. Moretti
    University Campus Bio-medico, Rome, Italy
    Ophthalmology,
  • E. Perrella
    University Campus Bio-medico, Rome, Italy
    Pathology,
  • S. Bonini
    University Campus Bio-medico, Rome, Italy
    Ophthalmology,
  • Footnotes
    Commercial Relationships  A. Iovieno, None; A. Micera, None; B. Stampachiacchiere, None; C. Moretti, None; E. Perrella, None; S. Bonini, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5016. doi:https://doi.org/
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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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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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 
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