Abstract
Uveal melanoma (UM) is the commonest primary intraocular malignancy in adults. There is limited published data on lipid production in UM. Here, we describe the clinical, histological, immunohistochemical, and molecular findings in a ciliochoroidal melanoma with lipid production and expression of the enzyme HMG-CoA reductase. This case highlights an unusual UM tumour phenotype with a high-risk molecular metastatic profile and discusses tumour lipogenesis and activation of the mevalonate pathway as a potential therapeutic target in managing lipidised ciliochoroidal UM.
References
1.
Amaro
A
, Gangemi
R
, Piaggio
F
, Angelini
G
, Barisione
G
, Ferrini
S
, et al. The biology of uveal melanoma.
Cancer Metastasis Rev. 2017
03;36(1):109-40. 2.
Aronow
ME
, Topham
AK
, Singh
AD
. Uveal Melanoma: 5-Year Update on Incidence, Treatment, and Survival (SEER 1973-2013)
. Ocul Oncol Pathol
. 2018
Apr
;4
(3
):145
–51
.
[PubMed]
2296-46813.
Virgili
G
, Gatta
G
, Ciccolallo
L
, Capocaccia
R
, Biggeri
A
, Crocetti
E
, et al.; EUROCARE Working Group
. Incidence of uveal melanoma in Europe
. Ophthalmology
. 2007
Dec
;114
(12
):2309
–15
.
[PubMed]
0161-64204.
Baenke
F
, Peck
B
, Miess
H
, Schulze
A
. Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development
. Dis Model Mech
. 2013
Nov
;6
(6
):1353
–63
.
[PubMed]
1754-84035.
Yavuzyigitoglu
S
, Kilic
E
, Vaarwater
J
, de Klein
A
, Paridaens
D
, Verdijk
RM
; Rotterdam Ocular Melanoma Study Group (ROMS)
. Lipomatous Change in Uveal Melanoma: Histopathological, Immunohistochemical and Cytogenetic Analysis
. Ocul Oncol Pathol
. 2016
Apr
;2
(3
):133
–5
.
[PubMed]
2296-46816.
Fiorentzis
M
, Kalirai
H
, Katopodis
P
, Coupland
SE
. Adipophilin expression in primary and metastatic uveal melanoma: a pilot study. Graefe’s archive for clinical and experimental ophthalmology =
. Albrecht Von Graefes Arch Klin Exp Ophthalmol
. 2017
May
;255
(5
):1049
–51
. 0065-61007.
Mayrhofer
M
, Viklund
B
, Isaksson
A
. Rawcopy: improved copy number analysis with Affymetrix arrays
. Sci Rep
. 2016
Oct
;6
(1
):36158
.
[PubMed]
2045-23228.
Richards
S
, Aziz
N
, Bale
S
, Bick
D
, Das
S
, Gastier-Foster
J
, et al.; ACMG Laboratory Quality Assurance Committee
. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology
. Genet Med
. 2015
May
;17
(5
):405
–24
.
[PubMed]
1098-36009.
Li
MM
, Datto
M
, Duncavage
EJ
, Kulkarni
S
, Lindeman
NI
, Roy
S
, et al. Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn. 2017
01;19(1):4-23.10.
Robertson
AG
, Shih
J
, Yau
C
, Gibb
EA
, Oba
J
, Mungall
KL
, et al. Integrative analysis identifies four molecular and clinical subsets in uveal melanoma.
Cancer cell. 2017
;32(2):204-20. e15. 11.
Bakhoum
MF
, Esmaeli
B
. Molecular Characteristics of Uveal Melanoma: Insights from the Cancer Genome Atlas (TCGA) Project
. Cancers (Basel)
. 2019
Jul
;11
(8
):1061
.
[PubMed]
2072-669412.
Vander Heiden
MG
, Cantley
LC
, Thompson
CB
. Understanding the Warburg effect: the metabolic requirements of cell proliferation
. Science
. 2009
May
;324
(5930
):1029
–33
.
[PubMed]
0036-807513.
Fischer
GM
, Vashisht Gopal
YN
, McQuade
JL
, Peng
W
, DeBerardinis
RJ
, Davies
MA
. Metabolic strategies of melanoma cells: Mechanisms, interactions with the tumor microenvironment, and therapeutic implications
. Pigment Cell Melanoma Res
. 2018
Jan
;31
(1
):11
–30
.
[PubMed]
1755-147114.
Fujimoto
M
, Matsuzaki
I
, Yamamoto
Y
, Yoshizawa
A
, Warigaya
K
, Iwahashi
Y
, et al. Adipophilin expression in cutaneous malignant melanoma
. J Cutan Pathol
. 2017
Mar
;44
(3
):228
–36
.
[PubMed]
0303-698715.
Drabarek
W
, Yavuzyigitoglu
S
, Obulkasim
A
, van Riet
J
, Smit
KN
, van Poppelen
NM
, et al. Multi-Modality Analysis Improves Survival Prediction in Enucleated Uveal Melanoma Patients.
Invest Ophthalmol Vis Sci. 2019
08;60(10):3595-605. 16.
Vichitvejpaisal
P
, Dalvin
LA
, Mazloumi
M
, Ewens
KG
, Ganguly
A
, Shields
CL
. Genetic Analysis of Uveal Melanoma in 658 Patients Using the Cancer Genome Atlas Classification of Uveal Melanoma as A, B, C, and D
. Ophthalmology
. 2019
Oct
;126
(10
):1445
–53
.
[PubMed]
0161-642017.
Gruenbacher
G
, Thurnher
M
. Mevalonate metabolism in cancer
. Cancer Lett
. 2015
Jan
;356
(2
2 Pt A
):192
–6
.
[PubMed]
0304-383518.
Gruenbacher
G
, Thurnher
M
. Mevalonate Metabolism in Cancer Stemness and Trained Immunity
. Front Oncol
. 2018
Sep
;8
:394
.
[PubMed]
2234-943X19.
Hager MH, Solomon KR, Freeman MR. The role of cholesterol in prostate cancer. Curr Opin Clin Nutr Metab Care. 2006 Jul;9(4):379–85. DOI: 10.1097/01.mco.0000232896.66791.62.
20.
Yeganeh
B
, Wiechec
E
, Ande
SR
, Sharma
P
, Moghadam
AR
, Post
M
, et al. Targeting the mevalonate cascade as a new therapeutic approach in heart disease, cancer and pulmonary disease
. Pharmacol Ther
. 2014
Jul
;143
(1
):87
–110
.
[PubMed]
0163-725821.
Likus
W
, Siemianowicz
K
, Bieńk
K
, Pakuła
M
, Pathak
H
, Dutta
C
, et al. Could drugs inhibiting the mevalonate pathway also target cancer stem cells?
Drug Resist Updat
. 2016
Mar
;25
:13
–25
.
[PubMed]
1368-764622.
Koohestanimobarhan
S
, Salami
S
, Imeni
V
, Mohammadi
Z
, Bayat
O
. Lipophilic statins antagonistically alter the major epithelial-to-mesenchymal transition signaling pathways in breast cancer stem-like cells via inhibition of the mevalonate pathway
. J Cell Biochem
. 2018
Sep
.
[PubMed]
1097-464423.
Gaist
D
, Hallas
J
, Friis
S
, Hansen
S
, Sørensen
HT
. Statin use and survival following glioblastoma multiforme
. Cancer Epidemiol
. 2014
Dec
;38
(6
):722
–7
.
[PubMed]
1877-782124.
Gray
RT
, Loughrey
MB
, Bankhead
P
, Cardwell
CR
, McQuaid
S
, O’Neill
RF
, et al. Statin use, candidate mevalonate pathway biomarkers, and colon cancer survival in a population-based cohort study
. Br J Cancer
. 2017
Jun
;116
(12
):1652
–9
.
[PubMed]
0007-092025.
Kobayashi
Y
, Kashima
H
, Wu
RC
, Jung
JG
, Kuan
JC
, Gu
J
, et al. Mevalonate Pathway Antagonist Suppresses Formation of Serous Tubal Intraepithelial Carcinoma and Ovarian Carcinoma in Mouse Models
. Clin Cancer Res
. 2015
Oct
;21
(20
):4652
–62
.
[PubMed]
1078-043226.
Kobayashi
Y
, Kashima
H
, Rahmanto
YS
, Banno
K
, Yu
Y
, Matoba
Y
, et al. Drug repositioning of mevalonate pathway inhibitors as antitumor agents for ovarian cancer
. Oncotarget
. 2017
Aug
;8
(42
):72147
–56
.
[PubMed]
1949-255327.
Göbel
A
, Thiele
S
, Browne
AJ
, Rauner
M
, Zinna
VM
, Hofbauer
LC
, et al. Combined inhibition of the mevalonate pathway with statins and zoledronic acid potentiates their anti-tumor effects in human breast cancer cells
. Cancer Lett
. 2016
May
;375
(1
):162
–71
.
[PubMed]
0304-383528.
Woschek
M
, Kneip
N
, Jurida
K
, Marzi
I
, Relja
B
. Simvastatin Reduces Cancerogenic Potential of Renal Cancer Cells via Geranylgeranyl Pyrophosphate and Mevalonate Pathway
. Nutr Cancer
. 2016
;68
(3
):420
–7
.
[PubMed]
0163-558129.
Iannelli
F
, Lombardi
R
, Milone
MR
, Pucci
B
, De Rienzo
S
, Budillon
A
, et al. Targeting Mevalonate Pathway in Cancer Treatment: repurposing of Statins
. Recent Patents Anticancer Drug Discov
. 2018
;13
(2
):184
–200
.
[PubMed]
1574-8928© 2020 S. Karger AG, Basel
2020
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