Increased expression of the retinoic acid-metabolizing enzyme CYP26A1 during the progression of cervical squamous neoplasia and head and neck cancer

BMC Research Notes

Gang-Hong Lee¹  Makoto Osanai¹ 

[1] Department of Pathology, Kochi University School of Medicine, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan

关键词: Immunohistochemistry;    Head and neck cancer;    Squamous cell carcinoma;    Squamous intraepithelial lesion;    Cervical squamous neoplasia;    Carcinogenesis;    Vitamin A deficiency;    Retinoic acid-metabolizing enzyme CYP26A1;    Retinoic acid;   

Others  :  1127338
DOI  :  10.1186/1756-0500-7-697

 received in 2014-06-16, accepted in 2014-10-02,  发布年份 2014

【 摘 要 】

Background

Retinoic acid (RA) is a critical regulator of cell differentiation, proliferation, and apoptosis in various cell types. Recently, the RA-metabolizing enzyme CYP26A1 (cytochrome P450, family 26, subfamily A, polypeptide 1) has been shown to have an oncogenic function in breast carcinogenesis. However, the relevance of elevated CYP26A1 expression in human cancers remains to be clarified.

Methods

We immunohistochemically examined the expression of CYP26A1 in cervical squamous cell carcinoma (SCC) and its precursors, including low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), as well as head and neck cancer (HNC). The association between CYP26A1 expression and a number of clinicopathological parameters was also evaluated.

Results

CYP26A1 was not expressed in normal cervical epithelium. CYP26A1 expression was present in LSIL but limited to basal and parabasal cells. HSIL cases exhibited strong nuclear expression of CYP26A1 and mixed cytoplasmic expression patterns with widely distributed expression toward the epithelial surface. Importantly, strong cytoplasmic staining of CYP26A1 was observed in 19 of 50 (38%) patients with cervical SCC. Elevated expression of CYP26A1 was significantly associated with younger age (<50 years) and lymph node involvement (pN). Similarly, CYP26A1 was not expressed in non-neoplastic tissues of the head and neck, but strong cytoplasmic staining of CYP26A1 was observed in 52 of 128 (41%) HNC cases. Such strong CYP26A1 expression was significantly associated with the primary tumor stage of carcinomas (pT) and the pathological tumor-node-metastasis (pTNM) stage in HNC.

Conclusion

Our results indicated an elevated CYP26A1 expression in malignant and precancerous dysplastic lesions of the human cervix, which also increased with the progression of cervical squamous neoplasia. In addition, this report is the first to demonstrate the increased expression of CYP26A1 in HNC and its significant correlation with primary tumor growth. These data suggested that CYP26A1 overexpression might contribute to the development and progression of cervical malignancies and squamous neoplasia of the head and neck.

【 授权许可】

   
2014 Osanai and Lee; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Tavassoli FA, Devilee P: Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon, France: International Agency for Research on Cancer Press; 2003.
• [2]Straight SW, Hinkle PM, Jewers RJ, McCance DJ: The E5 oncoprotein of human papilloma virus type 16 transforms fibroblasts and effects the downregulation of the epidermal growth factor receptor in keratinocytes. J Virol 1993, 67:4521-4532.
• [3]Zhang X, Dai B, Zhang B, Wang Z: Vitamin A and risk of cervical cancer: a meta-analysis. Gynecol Oncol 2012, 124:366-373.
• [4]Meyskens FL Jr, Manetta A: Prevention of cervical intraepithelial neoplasia and cervical cancer. Am J Clin Nutr 1995, 62:1417S-1419S.
• [5]La Vecchia C, Franceschi S, Decarli A, Gentile A, Fasoli M, Pampallona S, Tognoni G: Dietary vitamin A and the risk of invasive cervical cancer. Int J Cancer 1984, 34:319-322.
• [6]Meyskens FL Jr, Surwit E, Moon TE, Childers JM, Davis JR, Dorr RT, Johnson CS, Alberts DS: Enhancement of regression of cervical intraepithelial neoplasia II (moderate dysplasia) with topically applied all-trans-retinoic acid: a randomized trial. J Natl Cancer Inst 1994, 86:539-543.
• [7]Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011, 61:69-90.
• [8]Stewart BW, Kleihues P: World Cancer Report. Geneva: International Agency for Research on Cancer; 2003:232-236.
• [9]Forastiere A, Koch W, Trotti A, Sidransky D: Head and neck cancer. N Engl J Med 2001, 345:1890-1900.
• [10]Williams HK: Molecular pathogenesis of oral squamous cell carcinoma. Mod Pathol 2000, 53:165-172.
• [11]Braakhuis BJ, Tabor MP, Kummer JA, Leemans CR, Brakenhoff RH: A genetic explanation of Slaughter’s concept of field cancerization: evidence and clinical implications. Cancer Res 2003, 63:1727-1730.
• [12]Perez-Ordoñez B, Beauchemin M, Jordan RC: Molecular biology of squamous cell carcinoma of the head and neck. J Clin Pathol 2006, 59:445-453.
• [13]Osanai M, Sawada N, Lee GH: Oncogenic and cell survival properties of the retinoic acid metabolizing enzyme, CYP26A1. Oncogene 2010, 29:1135-1144.
• [14]Chang CL, Hong E, Lao-Sirieix P, Fitzgerald RC: A novel role for the retinoic acid-catabolizing enzyme CYP26A1 in Barrett’s associated adenocarcinoma. Oncogene 2008, 27:2951-2960.
• [15]Shelton DN, Sandoval IT, Eisinger A, Chidester S, Ratnayake A, Ireland CM, Jones DA: Up-regulation of CYP26A1 in adenomatous polyposis coli-deficient vertebrates via a WNT-dependent mechanism: implications for intestinal cell differentiation and colon tumor development. Cancer Res 2006, 66:7571-7577.
• [16]Sonneveld E, van den Brink CE, van der Leede BM, Schulkes RK, Petkovich M, van der Burg B, van der Saag PT: Human retinoic acid (RA) 4-hydroxylase (CYP26) is highly specific for all-trans-RA and can be induced through RA receptors in human breast and colon carcinoma cells. Cell Growth Diff 1998, 9:629-637.
• [17]Wolbach SB, Howe PR: Tissue changes following deprivation of fat-soluble A vitamin. J Exp Med 1925, 43:753-777.
• [18]Solomon D, Davey D, Kurman R, Moriarty A, O’Connor D, Prey M, Raab S, Sherman M, Wilbur D, Wright T Jr, Young N: The Bethesda System: terminology for reporting results of cervical cytology. JAMA 2001, 2002(287):2114-2119.
• [19]French AL, Kirstein LM, Massad LS, Semba RD, Minkoff H, Landesman S, Palefsky J, Young M, Anastos K, Cohen MH: Association of vitamin A deficiency with cervical squamous intraepithelial lesions in human immunodeficiency virus-infected women. J Infect Dis 2000, 182:1084-1089.
• [20]Wang Z, Boudjelal M, Kang S, Voorhees JJ, Fisher GJ: Ultraviolet irradiation of human skin causes functional vitamin A deficiency, preventable by all-trans retinoic acid pre-treatment. Nat Med 1999, 5:418-422.
• [21]Moody CA, Laimins LA: Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer 2010, 10:550-560.
• [22]Lu X, Feki A: Phenotypic features with p53 alterations related to human papillomavirus and prognostic evaluation in cervical cancer. Int J Gynecol Cancer 2006, 16:708-717.
• [23]Loudig O, Babichuk C, White J, Abu-Abed S, Mueller C, Petkovich M: Cytochrome P450RAI (CYP26) promoter: a distinct composite retinoic acid response element underlies the complex regulation of retinoic acid metabolism. Mol Endocrinol 2000, 14:1483-1497.
• [24]Berlin Grace VM, Niranjali Devaraj S, Radhakrishnan Pillai M, Devaraj H: HPV-induced carcinogenesis of the uterine cervix is associated with reduced serum ATRA level. Gynecol Oncol 2006, 103:113-119.
• [25]Murr G, Kostelić F, Donkić-Pavicić I, Grdinić B, Subić N: Comparison of the vitamin A blood serum level in patients with head-neck cancer and healthy persons. HNO 1988, 36:359-362.