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. 2020 Nov 20:10:589849.
doi: 10.3389/fonc.2020.589849. eCollection 2020.

The Macro-Autophagy-Related Protein Beclin-1 Immunohistochemical Expression Correlates With Tumor Cell Type and Clinical Behavior of Uveal Melanoma

Giuseppe Broggi  1 , Antonio Ieni  2 , Daniela Russo  3 , Silvia Varricchio  3 , Lidia Puzzo  1 , Andrea Russo  4 , Michele Reibaldi  4   5 , Antonio Longo  4 , Giovanni Tuccari  2 , Stefania Staibano  3 , Rosario Caltabiano  1
Affiliations

The Macro-Autophagy-Related Protein Beclin-1 Immunohistochemical Expression Correlates With Tumor Cell Type and Clinical Behavior of Uveal Melanoma

Giuseppe Broggi et al. Front Oncol. .

Abstract

Uveal melanoma, in spite of its rarity, represents the most common primitive intraocular malignant neoplasm of the adults; it affects choroid, ciliary bodied and iris and remains clinically silent for a long time, being accidentally discovered by routine ophthalmic exams. Prognosis of uveal melanoma is poor and frequently characterized by liver metastases, within 10-15 years from diagnosis. Autophagy is a multi-step catabolic process by which cells remove damaged organelles and proteins and recycle nutrients. It has been hypothesized that in early stages of tumorigenesis autophagy has a tumor suppressor role while, in more advanced stages, it may represent a survival mechanism of neoplastic cells in response to stress. Several proteins related to autophagy cascade have been investigated in numerous subtypes of human cancer, with overall controversal results. In this paper we studied the immunohistochemical expression of 3 autophagy related proteins (Beclin-1, p62 and ATG7) in a cohort of 85 primary uveal melanoma treated by primary enucleation (39 with metastasis and 46 non metastatic) and correlated their expression with clinico-pathological parameters and blood vascular microvessel density, in order to investigate the potential prognostic role of autophagy in this rare neoplasm. We found that high immunohistochemical levels of Beclin-1 correlated with a lower risk of metastasis and higher disease-free survival times, indicating a positive prognostic role for Beclin-1 in uveal melanoma. No statistically significative differences regarding the expression of ATG7 and p62 between metastatic and non metastatic patients was detected.

Keywords: Beclin-1; autophagy; immunohistochemistry; prognosis; uveal melanoma.

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Figures

Figure 1
Figure 1
Tumor parameters, disease free time, follow-up, beclin-1, p62 and ATG7 expression and MVD in primary uveal melanoma without metastasis.
Figure 2
Figure 2
Tumor parameters, disease free time, follow-up, beclin-1, p62 and ATG7 expression and MVD in primary uveal melanoma with metastasis.
Figure 3
Figure 3
Median (range) of demographics, tumor parameters, disease free time, follow-up, beclin-1, p62, and ATG7 expression and MVD in primary uveal melanoma without and with systemic metastasis.
Figure 4
Figure 4
High (A) and low (B) expression of Beclin-1 in uveal melanoma. (Immunoperoxidase stain; original magnifications 100×).
Figure 5
Figure 5
Number of uveal melanoma (with and without metastasis) with low and high beclin-1, p62, and ATG7 expression and MVD (n/mm2).
Figure 6
Figure 6
High (A) and low (B) expression of p62 in uveal melanoma. (Immunoperoxidase stain; original magnifications 100×).
Figure 7
Figure 7
High (A) and low (B) expression of ATG7 in uveal melanoma. (Immunoperoxidase stain; original magnifications 100×).
Figure 8
Figure 8
Kaplan–Meier survival analyses in patients with uveal melanomas with low and high Beclin-1 expression.
Figure 9
Figure 9
Kaplan–Meier survival analyses in patients with uveal melanomas with low and high p62 expression.
Figure 10
Figure 10
Kaplan–Meier survival analyses in patients with uveal melanomas with low and high ATG7 expression.
Figure 11
Figure 11
Kaplan–Meier survival analyses in patients with uveal melanomas with low and high MVD count.
Figure 12
Figure 12
Correlation analysis between beclin-1 IRS, MVD values and DFS.
See this image and copyright information in PMC

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