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Absence of nuclear Programmed cell death 4 as an indicator of poor prognosis in uveal melanoma patients
Author(s) -
Ahmed I.,
Kalirai H.,
Angi M.,
Coupland S.
Publication year - 2017
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2017.03643
Subject(s) - melanoma , immunohistochemistry , programmed cell death , pathology , malignancy , cytoplasm , choroid , cancer research , medicine , biology , apoptosis , microbiology and biotechnology , genetics , retina , neuroscience
Purpose Uveal melanoma ( UM ) is the most frequently occurring intraocular malignancy in adults. Arising from the uncontrolled proliferation of melanocytes in the choroid, ciliary body and iris, UM s have a strong propensity to metastasise to the liver, where they are fatal. In a previous study, proteomic examination of UM s at either a high or low risk of developing metastasis identified the down regulation of Programmed Cell Death 4 ( PDCD 4) levels with increasing metastatic risk. Methods This study examined PDCD 4 protein expression and subcellular localisation in UM patient samples by immunohistochemistry ( IHC ). 165 primary ( PUM ) and 18 metastatic UM ( MUM ) samples with full clinical, histological and genetic data were included in the study. Slides were assessed and scored according to (A) percentage of tumour cells with cytoplasmic PDCD 4 expression; (B) intensity of cytoplasmic staining and (C) percentage of PDCD 4 positive tumour nuclei. Results In PUM and MUM samples, PDCD 4 was localised primarily to the cytoplasm. An equal percentage of primary and metastatic samples expressed nuclear PDCD 4 (28%). Loss of nuclear PDCD 4 was strongly associated with factors associated with a poor prognosis, in particular, monosomy 3 (p = 0.014) and loss of nuclear BAP 1 (p = 0.012). PUM s with nuclear PDCD 4 in ≥10% of tumour cells had an improved survival time compared with PUM s with <10% nuclear expression of PDCD 4 (p = 0.105). Conclusions The tumour suppressor PDCD 4 shuttles between the nucleus and cytoplasm to exert its effects in normal cells. In PUM samples, an absence of nuclear PDCD 4 localisation was associated with a poor outcome. Further functional studies are necessary to determine how PDCD 4 localisation influences UM cell behaviour.