Top

Published in:

Open Access 01-12-2015 | Research article

Expression of retinoic acid-binding proteins and retinoic acid receptors in sebaceous cell carcinoma of the eyelids

Authors: Yueh-Ju Tsai, Shu-Ya Wu, Hsuan-Ying Huang, David Hui-Kang Ma, Nan-Kai Wang, Ching-Hsi Hsiao, Ching-Yi Cheng, Lung-Kun Yeh

Published in: BMC Ophthalmology | Issue 1/2015

Abstract

Background

Sebaceous cell carcinoma of the eyelid is a malignant tumor. However, the pathoetiology of sebaceous cell carcinoma is not clear. Retinoic acid (RA) signaling is essential for skin epidermal differentiation including the eyelids. In this study, we investigate the expression of β-catenin, RA-binding proteins and RA receptors in sebaceous cell carcinoma of the eyelid and try to estimate their influence on its pathoetiology.

Methods

Retrospective, noncomparative, consecutive interventional case series. Sixteen cases of eyelid sebaceous gland carcinoma who received tumor excision at our hospital between 2001 and 2011 were included. Immunohistochemical staining for β-catenin, cellular retinoic acid binding protein 1 (CRABP1), cellular retinoic acid binding protein 2 (CRABP2), fatty acid-binding protein 5 (FABP5), retinoic acid receptors (RAR-α, −β, −γ), and retinoid X receptors (RXR-α, −β, −γ) was performed on tissue samples obtained from tumor excision.

Results

Of the 16 sebaceous cell carcinoma cases reviewed, six were male and 10 female. The mean follow-up period was 6.7 ± 3.66 years (range, 0.3–13 years). Of these 16 cases, the expression of β-catenin was significantly increased in sebaceous cell carcinoma cases. CRABP1 was similarly expressed in the sebaceous cell carcinoma and control groups. CRABP2 and FABP5 were expressed in hair follicles of lid skin in both groups, whereas the CRABP2 and FABP5 were aberrantly expressed in the tumor cells of the sebaceous glands. Notably, the expression of retinoic acid receptor (RAR-β) and retinoid X receptors (RXR-β, −γ) was significantly upregulated in sebaceous cell carcinoma of the eyelids.

Conclusions

Our findings indicate that retinoic acid signaling is related to the pathogenesis of sebaceous cell carcinoma of the eyelids.

Buitrago W, Joseph AK. Sebaceous carcinoma- the great masquerader: emerging concepts in diagnosis and treatment. Dermatol Ther. 2008;21(6):459–66.CrossRefPubMed

Dasgupta T, Wilson LD, Yu JB. Retrospective review of 1349 cases of sebaceous carcinoma. Cancer. 2009;115:158–65.CrossRefPubMed

Sung D, Kaltreider SA, Gonzalez-Fernandez F. Early onset sebaceous carcinoma. Diagn Pathol. 2011;6:81.CrossRefPubMedPubMedCentral

Cohen PR, Kohn SR, Kurzrock R. Association of sebaceous gland tumors and internal malignancy: the Muir–Torre syndrome. Am J Med. 1991;90:606–13.CrossRefPubMed

Shalin SC, Lyle S, Calonje E, Lazar AJF. Sebaceous neoplasia and the Muir–Torre syndrome: important connections with clinical implications. Histopathology. 2010;56:133–47.CrossRefPubMedPubMedCentral

Finzi E, Blake MJ, Celano P, Skouge J, Diwan R. Cellular localization of retinoic acid receptor-gamma expression in normal and neoplastic skin. Am J Pathol. 1992;140:1463–71.PubMedPubMedCentral

Sporn MB, Roberts AB. Role of retinoids in differentiation and carcinogenesis. J Natl Cancer Inst. 1984;73:1381–7.PubMed

De Luca LM. Retinoids and their receptors in differentiation, embryogenesis and neoplasia. FASEB J. 1991;5:2924–33.PubMed

Lotan R. Retinoids and apoptosis: implications for cancer chemoprevention and therapy. J Natl Cancer Inst. 1995;87:1655–7.CrossRefPubMed

10.

Altucci L, Gronemeyer H. The promise of retinoids to fight against cancer. Nat Rev Cancer. 2001;1:181–93.CrossRefPubMed

11.

Collins CA, Watt FM. Dynamic regulation of retinoic acid-binding proteins in developing adult and neoplastic skin reveals roles for β-catenin and Notch signalling. Dev Biol. 2008;324:55–67.CrossRefPubMed

12.

Furuhashi M, Hotamisligil GS. Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov. 2008;7:489–503.CrossRefPubMedPubMedCentral

13.

Austinat M, Dunsch R, Wittekind C, Tannapfel A, Gebhardt R, Gaunitz F. Correlation between β-catenin mutations and expression of Wnt-signaling target genes in hepatocellular carcinoma. Mol Cancer. 2008;7:21.CrossRefPubMedPubMedCentral

14.

Chung GG, Zerkowski MP, Ocal IT, Dolled-Filhart M, Kang JY, Psyrri A, et al. β-Catenin and p53 analyses of a breast carcinoma tissue microarray. Cancer. 2004;100:2084–92.CrossRefPubMed

15.

Hayes MJ, Thomas D, Emmons A, Giordano TJ, Kleer CG. Genetic changes of Wnt pathway genes are common events in metaplastic carcinomas of the breast. Clin Cancer Res. 2008;14:4038–44.CrossRefPubMedPubMedCentral

16.

Doglioni C, Piccinin S, Demontis S, Cangi MG, Pecciarini L, Chiarelli C, et al. Alterations of β-catenin pathway in nonmelanoma skin tumors: loss of α-ABC nuclear reactivity correlates with the presence of β-catenin gene mutation. Am J Pathol. 2003;163:2277–87.CrossRefPubMedPubMedCentral

17.

Brabletz T, Jung A, Reu S, Porzner M, Hlubek F, Kunz-Schughart LA, et al. Variable β-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Natl Acad Sci U S A. 2001;98:10356–61.CrossRefPubMedPubMedCentral

18.

Chawla A, Repa JJ, Evans RM, Mangelsdorf DJ. Nuclear receptors and lipid physiology: opening the X-files. Science. 2001;294:1866–70.CrossRefPubMed

19.

Mark M, Ghyselinck NB, Chambon P. Function of retinoid nuclear receptors: lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis. Annu Rev Pharmacol Toxicol. 2006;46:451–80.CrossRefPubMed

20.

Zhang Y, Call MK, Yeh LK, Liu H, Kochel T, Wang IJ, et al. Aberrant expression of a beta-catenin gain-of-function mutant induces hyperplastic transformation in the mouse cornea. J Cell Sci. 2010;123(8):1285–94.CrossRefPubMedPubMedCentral

21.

Jayaraj P, Sen S, Kashyap S, Sharma A, Pushker N, Bajaj MS, et al. Does β-catenin have a role in pathogenesis of sebaceous cell carcinoma of the eyelid? Br J Ophthalmol. 2011;95:284–7.CrossRefPubMed

22.

Storch J, Corsico B. The emerging functions and mechanisms of mammalian fatty acid-binding proteins. Ann Rev Nutr. 2008;28:73–95.CrossRef

23.

Schug TT, Berry DC, Shaw NS, Travis SN, Noy N. Opposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors. Cell. 2007;129:723–33.CrossRefPubMedPubMedCentral

24.

Chakravarti N, Saadati HG, El-Naggar AK, Lotan R, Diba RE, Esmaeli B. Retinoid receptor subtypes in sebaceous cell carcinoma of the eyelid. Ophthal Plast Reconstr Surg. 2005;4:292–7.CrossRef

Title: Expression of retinoic acid-binding proteins and retinoic acid receptors in sebaceous cell carcinoma of the eyelids
Authors: Yueh-Ju Tsai
Shu-Ya Wu
Hsuan-Ying Huang
David Hui-Kang Ma
Nan-Kai Wang
Ching-Hsi Hsiao
Ching-Yi Cheng
Lung-Kun Yeh
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: BMC Ophthalmology / Issue 1/2015
Electronic ISSN: 1471-2415
DOI: https://doi.org/10.1186/s12886-015-0145-5

At a glance: The STEP trials

Springer Medicine

Expression of retinoic acid-binding proteins and retinoic acid receptors in sebaceous cell carcinoma of the eyelids

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2015

Is it necessary to cover the macular hole with the inverted internal limiting membrane flap in macular hole surgery? A case report

Metastatic endophthalmitis combined with subretinal abscess in a patient with diabetes mellitus—a case report

Intravitreal ranibizumab monotherapy to treat retinopathy of prematurity zone II, stage 3 with plus disease

Multimodal imaging findings in a case of severe Central Serous Chorioretinopathy in an uncomplicated pregnancy

Small-incision phacotrabeculectomy versus phacoemulsification in refractory acute primary angle closure with cataract

Significant role of the choroidal outer layer during recovery from choroidal thickening in Vogt-Koyanagi-Harada disease patients treated with systemic corticosteroids