피부 편평세포암종의 악성화 과정에서 G1/S 세포주기 조절 단백의 이상 발현
Alteration of G1/S Cell Cycle Regulatory Proteins in Carcinogenesis of Cutaneous Squamous Cell Carcinomas
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Background : Aberration of the cell cycle regulatory proteins has been reported to contribute to the development and progression of human malignancy. We studied the expression of G1/S cell cycle regulatory proteins to investigate the carcinogenesis in cutaneous squamous cell lesions. Methods : We evaluated the expressions of p16, pRb, cyclin D1 and Ki-67 protein by immunonohistochemistry in cases of normal skin (n=15), seborrheic keratosis (SK; n=26), actinic keratosis (AK; n=30), Bowen’s disease (BD; n=37), keratoacanthoma (KA; n= 23), and squamous cell carcinoma (SCC; n=22). Results : The Ki-67 expression gradually increased from SK, through AK, to BD. The expression of p16 was more increased in BD than that in AK. The decreased expressions of p16 and Rb, and the increased expression of cyclin D1 were observed to a greater degree in SCC than those in BD. The expressions of cyclin D1 and Ki-67 were higher in SCC than those in KA. Conclusions : The altered expressions of p16, Rb, and cyclin D1 were considered to be related to the carcinogenesis in the cutaneous squamous cell lesions. Therefore, immunohistochemical studies of the cell cycle regulatory proteins and a combined analysis may be helpful as an adjunct to the histomorphology in the diagnosis of cutaneous squamous cell lesions.
Abstract
Background : Aberration of the cell cycle regulatory proteins has been reported to contribute to the development and progression of human malignancy. We studied the expression of G1/S cell cycle regulatory proteins to investigate the carcinogenesis in cutaneous squamous cell lesions. Methods : We evaluated the expressions of p16, pRb, cyclin D1 and Ki-67 protein by immunonohistochemistry in cases of normal skin (n=15), seborrheic keratosis (SK; n=26), actinic keratosis (AK; n=30), Bowen’s disease (BD; n=37), keratoacanthoma (KA; n= 23), and squamous cell carcinoma (SCC; n=22). Results : The Ki-67 expression gradually increased from SK, through AK, to BD. The expression of p16 was more increased in BD than that in AK. The decreased expressions of p16 and Rb, and the increased expression of cyclin D1 were observed to a greater degree in SCC than those in BD. The expressions of cyclin D1 and Ki-67 were higher in SCC than those in KA. Conclusions : The altered expressions of p16, Rb, and cyclin D1 were considered to be related to the carcinogenesis in the cutaneous squamous cell lesions. Therefore, immunohistochemical studies of the cell cycle regulatory proteins and a combined analysis may be helpful as an adjunct to the histomorphology in the diagnosis of cutaneous squamous cell lesions.
참고문헌 (28)
- 정진룡, "Expression of p63, bcl-2, bcl-6 and p16 in Basal Cell Carcinoma andSquamous Cell Carcinoma of the Skin", The Korean Journal of Pathology, 39(2), pp.91~98 (2005), 대한병리학회
- Nilsson K, "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, 17, pp.1464~1474 (2003)
- Salama ME, "p16INKa expression in actinic keratosis and Bowen’s disease", Br J Dermatol, 149, pp.1006~1012 (2003)
- Burnworth B, "The multi-step process of human skin carcinogenesis: a role for p53, cyclin D1, hTERT, p16, and TSP-1", Eur J Cell Biol, 86, pp.763~780 (2007)
- Hur HK, "Expression of pRb, p16, cyclin D1 and cyclin E in infiltrating duct carcinoma of the breast", Korean J Pathol, 35, pp.416~423 (2001)
- 한선희, "방광의 요로상피암종에서 p16, Rb, FHIT 단백 발현에 대한 연구", The Korean Journal of Pathology, 42(5), pp.294~298 (2008), 대한병리학회
- 김지연, "난소 상피 종양에서 G1", S 세포주기 조절단백의 변화, 2006, pp.40(4), 274~281[DOI]
- 이종실, "자궁목 병변에서 p16, p53 단백과 Ki-67의 발현", The Korean Journal of Pathology, 38(4), pp.238~243 (2004), 대한병리학회
- Mortier L, "Progression of actinic keratosis to squamous cell carcinoma of the skin correlates with deletion of the 9p21 region encoding the p16 (INK4a) tumor suppressor", Cancer Lett, 176, pp.205~214 (2002)
- Brown VL, "p16INK4a and p14ARF tumor suppressor genes are commonly inactivated in cutaneous squamous cell carcinoma", J Invest Dermatol, 122, pp.1284~1292 (2004)
- Hodges A, "Immunohistochemical comparison of p16 expression in actinic keratoses and squamous cell carcinomas of the skin", Mod Pathol, 15, pp.1121~1125 (2002)
- Conscience I, "P16 is overexpressed in cutaneous carcinomas located on sun-exposed areas", Eur J Dermatol, 16, pp.518~522 (2006)
- Ruiz S, "Unexpected roles for pRb in mouse skin carcinogenesis", Cancer Res, 65, pp.9678~9686 (2005)
- Robles AI, "Early overexpression of cyclin D1 protein in mouse skin carcinogenesis", Carcinogenesis, 16, pp.781~786 (1995)
- Bianchi AB, "Overexpression of cyclin D1 in mouse skin carcinogenesis", Oncogene, 8, pp.1127~1133 (1993)
- Edwards MJ, "Retinoblastoma gene expression in human non-melanoma skin cancer", J Cutan Pathol, 30, pp.479~485 (2003)
- Liang SB, "Overexpression of cyclin D1 in nonmelanocytic skin cancer", Virchows Arch, 436, pp.370~376 (2000)
- Brown DC, "Monoclonal antibody Ki-67: its use in histopathology", Histopathology, 17, pp.489~503 (1990)
- Kanitakis J, "Proliferation markers Ki67 and PCNA in cutaneous squamous cell carcinomas:lack of prognostic value", Br J Dermatol, 136, pp.643~644 (1997)
- Scurry J, "Ki67 expression in lichen sclerosus of vulva in patients with and without associated squamous cell carcinoma", Histopathology, 32, pp.399~404 (1998)
- Shimizu T, "Prognostic significance of expression of p53 protein and Ki-67 antigen in well-differentiated squamous cell carcinoma of the skin", J Dermatol, 26, pp.837~840 (1999)
- Baum HP, "Expression of proliferation-associated proteins (proliferating cell nuclear antigen and Ki-67 antigen) in Bowen’s disease", Br J Dermatol, 131, pp.231~236 (1994)
- Chen S, "Increased expression of an epidermal stem cell marker, cytokeratin 19, in cutaneous squamous cell carcinoma", Br J Dermatol, 159, pp.952~955 (2008)
- Kim L, "Histological and immunohistochemical characteristics of keratoacanthoma and well differentiated squamous cell carcinoma", Korean J Pathol, 34, pp.145~153 (2000)
- Clausen OP, "Are keratoacanthomas variants of squamous cell carcinomas? A comparison of chromosomal aberrations by comparative genomic hybridization", J Invest Dermatol, 126, pp.2308~2315 (2006)
- Beham A, "Keratoacanthoma:a clinically distinct variant of well differentiated squamous cell carcinoma", Adv Anat Pathol, 5, pp.269~280 (1998)
- Connolly M, "Immunohistochemical staining for the differentiation of subungual keratoacanthoma from subungual squamous cell carcinoma", Clin Exp Dermatol, 33, pp.625~628 (2008)
- Kaabipour E, "p16 expression in keratoacanthomas and squamous cell carcinomas of the skin: an immunohistochemical study", Arch Pathol Lab Med, 130, pp.69~73 (2006)