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Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 10/2006

01-10-2006 | Laboratory Investigation

Expression of p63 and p16 in primary and recurrent pterygia

Authors: Fernando S. Ramalho, Claudia Maestri, Leandra N. Z. Ramalho, Alfredo Ribeiro-Silva, Erasmo Romão

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 10/2006

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Abstract

Background

p63 and p16 have been described as stem-cell markers of squamous epithelium. In an attempt to obtain new insights into the pathogenesis of pterygium, this study aims to evaluate the relationship between p63 and p16 expression in primary and recurrent pterygia.

Methods

Samples of primary (n=56) and recurrent (n=14) pterygia and normal bulbar conjunctival tissue (n=11) were submitted to immunohistochemical study to evaluate the expression of p63 and p16 in these tissues.

Results

Most of the cells stained for p63 were located in the basal layer of the normal conjunctiva, in the lower two-thirds of the epithelium of primary pterygia, and throughout all epithelial layers of recurrent pterygia. In normal conjunctivae, p16 expression was rarely expressed. Primary and recurrent pterygium groups exhibited increased p16 expression, with cytoplasmic staining in the primary group, and cytoplasmic or nuclear staining in the recurrent group.

Conclusion

The overexpression of p63 and p16 observed in the present study reinforces likelihood of involvement of these genes in the pathogenesis of pterygium, perhaps related to the intense cellular turnover with substitution of superficial epithelial cells by less differentiated forms. This loss of normal cellular differentiation of the epithelial layers could explain the high rates of recurrence overall in the recurrent pterygia.
Literature
1.
go back to reference Au NH, Gown AM, Cheang M, Huntsman D, Yorida E, Elliott WM, Flint J, English J, Gilks CB, Grimes HL (2004) p63 expression in lung carcinoma: a tissue microarray study of 408 cases. Appl Immunohistochem Mol Morphol 12:240–247PubMed Au NH, Gown AM, Cheang M, Huntsman D, Yorida E, Elliott WM, Flint J, English J, Gilks CB, Grimes HL (2004) p63 expression in lung carcinoma: a tissue microarray study of 408 cases. Appl Immunohistochem Mol Morphol 12:240–247PubMed
2.
go back to reference Austin P, Jakobiec FA, Iwamoto T (1983) Elastodysplasia and elastodystrophy as the pathologic bases of ocular pterygia and pinguecula. Ophthalmology 90:96–109PubMed Austin P, Jakobiec FA, Iwamoto T (1983) Elastodysplasia and elastodystrophy as the pathologic bases of ocular pterygia and pinguecula. Ophthalmology 90:96–109PubMed
3.
go back to reference Auw-Haedrich C, Sundmacher R, Freudenberg N, Spelsberg H, Feltgen N, Maier P, Reinhard T (2005) Expression of p63 in conjunctival intraepithelial neoplasia and squamous cell carcinoma. Graefes Arch Clin Exp Ophthalmol 15:1–8 Auw-Haedrich C, Sundmacher R, Freudenberg N, Spelsberg H, Feltgen N, Maier P, Reinhard T (2005) Expression of p63 in conjunctival intraepithelial neoplasia and squamous cell carcinoma. Graefes Arch Clin Exp Ophthalmol 15:1–8
4.
go back to reference Clear AS, Chirambo MC, Hutt MSR (1979) Solar keratosis, pterygium, and squamous cell carcionoma of the conjunctiva in Malawi. Br J Ophthalmol 63:102–109PubMedCrossRef Clear AS, Chirambo MC, Hutt MSR (1979) Solar keratosis, pterygium, and squamous cell carcionoma of the conjunctiva in Malawi. Br J Ophthalmol 63:102–109PubMedCrossRef
5.
go back to reference Coroneo MT, Di Girolamo N, Wakefield D (1999) The pathogenesis of pterygia. Curr Opin Opthalmol 10:282–288CrossRef Coroneo MT, Di Girolamo N, Wakefield D (1999) The pathogenesis of pterygia. Curr Opin Opthalmol 10:282–288CrossRef
6.
go back to reference Coroneo MT (1993) Pterygium as an early indicator of ultraviolet insolation: a hypothesis. Br J Ophthalmol 77:734–739PubMedCrossRef Coroneo MT (1993) Pterygium as an early indicator of ultraviolet insolation: a hypothesis. Br J Ophthalmol 77:734–739PubMedCrossRef
7.
go back to reference Di Como CJ, Urist MJ, Babayan I, Drobnjak M, Hedvat CV, Teruya-Feldstein J, Pohar K, Hoos A, Cordon-Cardo C (2002) p63 expression profiles in human normal and tumor tissues. Clin Cancer Res 8:494–501PubMed Di Como CJ, Urist MJ, Babayan I, Drobnjak M, Hedvat CV, Teruya-Feldstein J, Pohar K, Hoos A, Cordon-Cardo C (2002) p63 expression profiles in human normal and tumor tissues. Clin Cancer Res 8:494–501PubMed
8.
go back to reference Di Girolamo N, Coroneo MT, Wakefield D (2003) UVB-elicited induction of MMP-1 expression in human ocular surface epithelial cells is mediated through the ERK1/2 MAPK-dependent pathway. Invest Ophthalmol Vis Sci 11:4705–4714CrossRef Di Girolamo N, Coroneo MT, Wakefield D (2003) UVB-elicited induction of MMP-1 expression in human ocular surface epithelial cells is mediated through the ERK1/2 MAPK-dependent pathway. Invest Ophthalmol Vis Sci 11:4705–4714CrossRef
9.
go back to reference Di Iorio E, Barbaro V, Ruzza A, Ponzin D, Pellegrini G, De Luca M (2005) Isoforms of DeltaNp63 and the migration of ocular limbal cells in human corneal regeneration. Proc Natl Acad Sci USA 102:9523–9528CrossRefPubMed Di Iorio E, Barbaro V, Ruzza A, Ponzin D, Pellegrini G, De Luca M (2005) Isoforms of DeltaNp63 and the migration of ocular limbal cells in human corneal regeneration. Proc Natl Acad Sci USA 102:9523–9528CrossRefPubMed
10.
go back to reference Dushku N, Reid TW (1994) Immunohistochemical evidence that human pterygia originate from the invasion of vimentin-expressing altered limbal epithelial basal cells. Curr Eye Res 13:473–481PubMedCrossRef Dushku N, Reid TW (1994) Immunohistochemical evidence that human pterygia originate from the invasion of vimentin-expressing altered limbal epithelial basal cells. Curr Eye Res 13:473–481PubMedCrossRef
11.
go back to reference Gologan O, Barnes EL, Hunt JL (2005) Potential diagnostic use of p16INK4A, a new marker that correlates with dysplasia in oral squamoproliferative lesions. Am J Surg Pathol 6:792–796 Gologan O, Barnes EL, Hunt JL (2005) Potential diagnostic use of p16INK4A, a new marker that correlates with dysplasia in oral squamoproliferative lesions. Am J Surg Pathol 6:792–796
12.
go back to reference Hodges A, Smoller BR (2002) Immunohistochemical comparison of p16 expression in actinic keratoses and squamous cell carcinomas of the skin. Mod Pathol 11:1121–1125CrossRef Hodges A, Smoller BR (2002) Immunohistochemical comparison of p16 expression in actinic keratoses and squamous cell carcinomas of the skin. Mod Pathol 11:1121–1125CrossRef
13.
go back to reference Hussein MR (2005) Ultraviolet radiation and skin cancer: molecular mechanisms. J Cutan Pathol 3:191–205CrossRef Hussein MR (2005) Ultraviolet radiation and skin cancer: molecular mechanisms. J Cutan Pathol 3:191–205CrossRef
14.
go back to reference Irwin MS, Kaelin WG (2001) P53 family update: p73 and p63 develop their own identities. Cell Growth Differ 12:337–349PubMed Irwin MS, Kaelin WG (2001) P53 family update: p73 and p63 develop their own identities. Cell Growth Differ 12:337–349PubMed
15.
go back to reference Kaufmann O, Fietze E, Mengs J, Dietel M (2001) Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas. Am J Clin Pathol 116:823–830CrossRefPubMed Kaufmann O, Fietze E, Mengs J, Dietel M (2001) Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas. Am J Clin Pathol 116:823–830CrossRefPubMed
16.
go back to reference Maisse C, Guerrieri P, Melino G (2003) P73 and p63 protein stability: the way to regulate function? Biochem Pharmacol 66:1555–1561CrossRefPubMed Maisse C, Guerrieri P, Melino G (2003) P73 and p63 protein stability: the way to regulate function? Biochem Pharmacol 66:1555–1561CrossRefPubMed
17.
go back to reference Massion PP, Taflan PM, Jamshedur Rahman SM, Yildiz P, Shyr Y, Edgerton ME, Westfall MD, Roberts JR, Pietenpol JA, Carbone DP, Gonzalez AL (2003) Significance of p63 amplification and overexpression in lung cancer development and prognosis. Cancer Res 21:7113–7121 Massion PP, Taflan PM, Jamshedur Rahman SM, Yildiz P, Shyr Y, Edgerton ME, Westfall MD, Roberts JR, Pietenpol JA, Carbone DP, Gonzalez AL (2003) Significance of p63 amplification and overexpression in lung cancer development and prognosis. Cancer Res 21:7113–7121
18.
go back to reference Murphy N, Ring M, Heffron CC, King B, Killalea AG, Hughes C, Martin CM,McGuinness E, Sheils O, O’Leary JJ (2005) p16INK4A, CDC6, and MCM5: predictive biomarkers in cervical preinvasive neoplasia and cervical cancer. J Clin Pathol 5:525–534CrossRef Murphy N, Ring M, Heffron CC, King B, Killalea AG, Hughes C, Martin CM,McGuinness E, Sheils O, O’Leary JJ (2005) p16INK4A, CDC6, and MCM5: predictive biomarkers in cervical preinvasive neoplasia and cervical cancer. J Clin Pathol 5:525–534CrossRef
19.
go back to reference Nilsson K, Svensson S, Landberg G (2004) Retinoblastoma protein function and p16INK4a expression in actinic keratosis, squamous cell carcinoma in situ and invasive squamous cell carcinoma of the skin and links between p16INK4a expression and infiltrative behavior. Mod Pathol 12:1464–1474CrossRef Nilsson K, Svensson S, Landberg G (2004) Retinoblastoma protein function and p16INK4a expression in actinic keratosis, squamous cell carcinoma in situ and invasive squamous cell carcinoma of the skin and links between p16INK4a expression and infiltrative behavior. Mod Pathol 12:1464–1474CrossRef
20.
go back to reference Pavey S, Conroy S, Russell T, Gabrielli B (1999) Ultraviolet radiation induces p16CDKN2A expression in human skin. Cancer Res 17:4185–4189 Pavey S, Conroy S, Russell T, Gabrielli B (1999) Ultraviolet radiation induces p16CDKN2A expression in human skin. Cancer Res 17:4185–4189
21.
go back to reference Reis-Filho JS, Simpson PT, Martins A, Preto A, Gartner F, Schmitt FC (2003) Distribution of p63, cytokeratins 5/6 and cytokeratin 14 in 51 normal and 400 neoplastic human tissue samples using TARP-4 multi-tumor tissue microarray. Virchows Arch 443:122–132CrossRefPubMed Reis-Filho JS, Simpson PT, Martins A, Preto A, Gartner F, Schmitt FC (2003) Distribution of p63, cytokeratins 5/6 and cytokeratin 14 in 51 normal and 400 neoplastic human tissue samples using TARP-4 multi-tumor tissue microarray. Virchows Arch 443:122–132CrossRefPubMed
22.
go back to reference Reis-Filho JS, Torio B, Albergaria A, Schmitt FC (2002) P63 expression in normal skin and usual cutaneous carcinomas. J Cutan Pathol 9:517–523CrossRef Reis-Filho JS, Torio B, Albergaria A, Schmitt FC (2002) P63 expression in normal skin and usual cutaneous carcinomas. J Cutan Pathol 9:517–523CrossRef
23.
go back to reference Sakoonwatanyoo P, Tan DT, Smith DR (2004) Expression of p63 in pterygium and normal conjunctiva. Cornea 1:67–70CrossRef Sakoonwatanyoo P, Tan DT, Smith DR (2004) Expression of p63 in pterygium and normal conjunctiva. Cornea 1:67–70CrossRef
24.
go back to reference Trink B, Okami K, Wu L, Sriuranpong V, Jen J, Sidransky D (1998) A new human p53 homologue. Nat Med 4:747–748CrossRefPubMed Trink B, Okami K, Wu L, Sriuranpong V, Jen J, Sidransky D (1998) A new human p53 homologue. Nat Med 4:747–748CrossRefPubMed
25.
go back to reference Wang IJ, Hu FR, Chen PJ, Lin CT (2000) Mechanism of abnormal elastin gene expression in the pinguecular part of pterygia. Am J Pathol 4:1269–1276 Wang IJ, Hu FR, Chen PJ, Lin CT (2000) Mechanism of abnormal elastin gene expression in the pinguecular part of pterygia. Am J Pathol 4:1269–1276
26.
go back to reference Westfall MD, Pietenpol JA (2004) P63: molecular complexity in development and cancer. Carcinogenesis 25:857–864CrossRefPubMed Westfall MD, Pietenpol JA (2004) P63: molecular complexity in development and cancer. Carcinogenesis 25:857–864CrossRefPubMed
27.
go back to reference Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dotsch V, Andrews NC, Caput D, McKeon F (1998) p63, a p53 homolog at 3q27–29, encodes multiple products with transactivating, death-inducing, and dominant negative activities. Mol Cell 2:305–316CrossRefPubMed Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dotsch V, Andrews NC, Caput D, McKeon F (1998) p63, a p53 homolog at 3q27–29, encodes multiple products with transactivating, death-inducing, and dominant negative activities. Mol Cell 2:305–316CrossRefPubMed
Metadata
Title
Expression of p63 and p16 in primary and recurrent pterygia
Authors
Fernando S. Ramalho
Claudia Maestri
Leandra N. Z. Ramalho
Alfredo Ribeiro-Silva
Erasmo Romão
Publication date
01-10-2006
Publisher
Springer-Verlag
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 10/2006
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-006-0287-5

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