Variations in the expression of TIMP1, TIMP2 and TIMP3 in cutaneous melanoma with regression and their possible function as prognostic predictors

Zurac,Sabina; Neagu,Monica; Constantin,Carolina; Cioplea,Mirela; Nedelcu,Roxana; Bastian,Alexandra; Popp,Cristiana; Nichita,Luciana; Andrei,Razvan; Tebeica,Tiberiu; Tanase,Cristiana; Chitu,Virginia; Caruntu,Constantin; Ghita,Mihaela; Popescu,Catalin; Boda,Daniel; Mastalier,Bogdan; Maru,Nicoleta; Daha,Claudiu; Andreescu,Bogdan; Marinescu,Ioan; Rebosapca,Adrian; Staniceanu,Florica; Negroiu,Gabriela; Ion,Daniela A.; Nikitovic,Dragana; Tzanakakis,George N.; Spandidos,Demetrios A.; Tsatsakis,Aristidis M.

doi:10.3892/ol.2016.4391

Variations in the expression of TIMP1, TIMP2 and TIMP3 in cutaneous melanoma with regression and their possible function as prognostic predictors

Authors:
- Sabina Zurac
- Monica Neagu
- Carolina Constantin
- Mirela Cioplea
- Roxana Nedelcu
- Alexandra Bastian
- Cristiana Popp
- Luciana Nichita
- Razvan Andrei
- Tiberiu Tebeica
- Cristiana Tanase
- Virginia Chitu
- Constantin Caruntu
- Mihaela Ghita
- Catalin Popescu
- Daniel Boda
- Bogdan Mastalier
- Nicoleta Maru
- Claudiu Daha
- Bogdan Andreescu
- Ioan Marinescu
- Adrian Rebosapca
- Florica Staniceanu
- Gabriela Negroiu
- Daniela A. Ion
- Dragana Nikitovic
- George N. Tzanakakis
- Demetrios A. Spandidos
- Aristidis M. Tsatsakis
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Affiliations: Department of Pathology, Colentina University Hospital, Bucharest 020125, Romania, Department of Immunology, ‘Victor Babes’ National Institute of Pathology, Bucharest 050096, Romania, Department of Physiology, ‘Carol Davila’ University of Medicine and Pharmacy, Bucharest 050474, Romania, Institute of Biochemistry of Romanian Academy, Bucharest 060031, Romania, Department of Anatomy‑Histology‑Embryology, Faculty of Medicine, University of Crete, Heraklion 71003, Greece, Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion 71409, Greece, Department of Forensic Sciences and Toxicology, Medical School, University of Crete, Heraklion 71003, Greece
Published online on: March 29, 2016 https://doi.org/10.3892/ol.2016.4391
Pages: 3354-3360
Copyright: © Zurac et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Regression in melanoma is a frequent biological event of uncertain prognostic value as the lesion exhibits heterogeneous phenotypical features, both at the morphological and immunohistochemical level. In the present study, we examined the expression of tissue inhibitors of metalloproteinases (TIMP1, TIMP2 and TIMP3) in melanoma with regression. We specifically examined the expression levels of these TIMPs in regressed components (RC) and non‑regressed components (NRC) of the tumor and compared their expression levels with those in non‑regressed melanomas. We found that TIMP1 was overexpressed in the NRC of melanomas with partial regression (PR) compared with the NRC in melanomas with segmental regression (SR) (P=0.011). TIMP2 was overexpressed in the NRC of melanomas with PR compared with the NRC in melanomas with SR (PR/SR, P=0.009); or compared with the NRC in melanomas with simultaneous SR‑PR (P=0.002); or compared with melanomas without regression (absence of regression) (P=0.037). Moreover, TIMP3 was overexpressed in the NRC of all melanomas with SR as compared to the RC component (P=0.007). Our findings on the differential expression of TIMP1, TIMP2 and TIMP3 in melanomas with regression support the hypothesis that the morphological differences identified in the melanoma regression spectrum may have a correlation with prognosis. This may explain the controversial findings within the literature concerning the biological and prognostic role of regression in melanoma.

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