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BMC Cancer
Published in: BMC Cancer 1/2008

Open Access 01-12-2008 | Research article

The clinicopathological and prognostic impact of 14-3-3 sigma expression on vulvar squamous cell carcinomas

Authors: Zhihui Wang, Claes G Tropè, Zhenhe Suo, Gunhild Trøen, Guanrui Yang, Jahn M Nesland, Ruth Holm

Published in: BMC Cancer | Issue 1/2008

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Abstract

Background

14-3-3 sigma (σ) promotes G2/M cell cycle arrest by sequestering cyclin B1-CDC2 complex in cytoplasm. Down-regulation of 14-3-3σ, which has been demonstrated in various carcinomas, may contribute to malignant transformation. However, the exact role of 14-3-3σ in the pathogenesis of vulvar carcinoma is not fully characterized, and the prognostic impact of 14-3-3σ protein expression is still unknown.

Methods

We investigated the 14-3-3σ expression in a series of 302 vulvar squamous cell carcinomas using immunohistochemistry and its associations with clinicopathological factors and clinical outcome.

Results

In cytoplasm, nucleus and cytoplasm/nucleus of vulvar carcinomas high 14-3-3σ protein expression was found in 72%, 59% and 75% of the carcinomas, respectively, and low levels in 28%, 41% and 25% of the cases, respectively. High level of 14-3-3σ in cytoplasm, nucleus and cytoplasm/nucleus was significantly correlated to large tumor diameter (p = 0.001, p = 0.002 and p = 0.001, respectively) and deep invasion (p = 0.01, p = 0.001 and p = 0.007, respectively). Variations of 14-3-3σ protein expression were not associated to disease-specific survival.

Conclusion

Our results indicate that 14-3-3σ may be involved in the development of a subset of vulvar squamous cell carcinomas by down-regulation of 14-3-3σ protein. Neither cytoplasmic nor nuclear level of 14-3-3σ expression was associated with prognosis.
Appendix
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Literature
1.
Coulter J, Gleeson N: Local and regional recurrence of vulval cancer: management dilemmas. Best Pract Res Clin Obstet Gynaecol. 2003, 17: 663-681. 10.1016/S1521-6934(03)00050-6.CrossRefPubMed
2.
Jones RW, Baranyai J, Stables S: Trends in squamous cell carcinoma of the vulva: the influence of vulvar intraepithelial neoplasia. Obstet Gynecol. 1997, 90: 448-452. 10.1016/S0029-7844(97)00298-6.CrossRefPubMed
3.
Messing MJ, Gallup DG: Carcinoma of the vulva in young women. Obstet Gynecol. 1995, 86: 51-54. 10.1016/0029-7844(95)00101-V.CrossRefPubMed
4.
Tyring SK: Vulvar squamous cell carcinoma: guidelines for early diagnosis and treatment. Am J Obstet Gynecol. 2003, 189: S17-S23. 10.1067/S0002-9378(03)00792-0.CrossRefPubMed
5.
Qi W, Liu X, Qiao D, Martinez JD: Isoform-specific expression of 14-3-3 proteins in human lung cancer tissues. Int J Cancer. 2005, 113: 359-363. 10.1002/ijc.20492.CrossRefPubMed
6.
Yaffe MB, Rittinger K, Volinia S, Caron PR, Aitken A, Leffers H, et al: The structural basis for 14-3-3:phosphopeptide binding specificity. cell. 1997, 91: 961-971. 10.1016/S0092-8674(00)80487-0.CrossRefPubMed
7.
Dougherty MK, Morrison DK: Unlocking the code of 14-3-3. J Cell Sci. 2004, 117: 1875-1884. 10.1242/jcs.01171.CrossRefPubMed
8.
Fu H, Subramanian RR, Masters SC: 14-3-3 proteins: structure, function, and regulation. Annu Rev Pharmacol Toxicol. 2000, 40: 617-647. 10.1146/annurev.pharmtox.40.1.617.CrossRefPubMed
9.
Mackintosh C: Dynamic interactions between 14-3-3 proteins and phosphoproteins regulate diverse cellular processes. Biochem J. 2004, 381: 329-342. 10.1042/BJ20031332.CrossRefPubMedPubMedCentral
10.
Hermeking H, Lengauer C, Polyak K, He TC, Zhang L, Thiagalingam S, et al: 14-3-3 sigma is a p53-regulated inhibitor of G2/M progression. Mol cell. 1997, 1: 3-11. 10.1016/S1097-2765(00)80002-7.CrossRefPubMed
11.
Lakin ND, Jackson SP: Regulation of p53 in response to DNA damage. Oncogene. 1999, 18: 7644-7655. 10.1038/sj.onc.1203015.CrossRefPubMed
12.
Taylor WR, Stark GR: Regulation of the G2/M transition by p53. Oncogene. 2001, 20: 1803-1815. 10.1038/sj.onc.1204252.CrossRefPubMed
13.
Laronga C, Yang HY, Neal C, Lee MH: Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression. J Biol Chem. 2000, 275: 23106-23112. 10.1074/jbc.M905616199.CrossRefPubMed
14.
Chan TA, Hermeking H, Lengauer C, Kinzler KW, Vogelstein B: 14-3-3Sigma is required to prevent mitotic catastrophe after DNA damage. Nature. 1999, 401: 616-620. 10.1038/44188.CrossRefPubMed
15.
Ferguson AT, Evron E, Umbricht CB, Pandita TK, Chan TA, Hermeking H, et al: High frequency of hypermethylation at the 14-3-3 sigma locus leads to gene silencing in breast cancer. Proc Natl Acad Sci USA. 2000, 97: 6049-6054. 10.1073/pnas.100566997.CrossRefPubMedPubMedCentral
16.
Iwata N, Yamamoto H, Sasaki S, Itoh F, Suzuki H, Kikuchi T, et al: Frequent hypermethylation of CpG islands and loss of expression of the 14-3-3 sigma gene in human hepatocellular carcinoma. Oncogene. 2000, 19: 5298-5302. 10.1038/sj.onc.1203898.CrossRefPubMed
17.
Lodygin D, Yazdi AS, Sander CA, Herzinger T, Hermeking H: Analysis of 14-3-3sigma expression in hyperproliferative skin diseases reveals selective loss associated with CpG-methylation in basal cell carcinoma. Oncogene. 2003, 22: 5519-5524. 10.1038/sj.onc.1206854.CrossRefPubMed
18.
Lodygin D, Diebold J, Hermeking H: Prostate cancer is characterized by epigenetic silencing of 14-3-3sigma expression. Oncogene. 2004, 23: 9034-9041. 10.1038/sj.onc.1208004.CrossRefPubMed
19.
Moreira JM, Gromov P, Celis JE: Expression of the tumor suppressor protein 14-3-3 sigma is down-regulated in invasive transitional cell carcinomas of the urinary bladder undergoing epithelial-to-mesenchymal transition. Mol Cell Proteomics. 2004, 3: 410-419. 10.1074/mcp.M300134-MCP200.CrossRefPubMed
20.
Suzuki H, Itoh F, Toyota M, Kikuchi T, Kakiuchi H, Imai K: Inactivation of the 14-3-3 sigma gene is associated with 5' CpG island hypermethylation in human cancers. Cancer Res. 2000, 60: 4353-4357.PubMed
21.
Yatabe Y, Osada H, Tatematsu Y, Mitsudomi T, Takahashi T: Decreased expression of 14-3-3sigma in neuroendocrine tumors is independent of origin and malignant potential. Oncogene. 2002, 21: 8310-8319. 10.1038/sj.onc.1206014.CrossRefPubMed
22.
Simpson PT, Gale T, Reis-Filho JS, Jones C, Parry S, Steele D, et al: Distribution and significance of 14-3-3sigma, a novel myoepithelial marker, in normal, benign, and malignant breast tissue. J Pathol. 2004, 202: 274-285. 10.1002/path.1530.CrossRefPubMed
23.
Ito K, Suzuki T, Akahira J, Sakuma M, Saitou S, Okamoto S, et al: 14-3-3sigma in endometrial cancer – a possible prognostic marker in early-stage cancer. Clin Cancer Res. 2005, 11: 7384-7391. 10.1158/1078-0432.CCR-05-0187.CrossRefPubMed
24.
Perathoner A, Pirkebner D, Brandacher G, Spizzo G, Stadlmann S, Obrist P, et al: 14-3-3sigma expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients. Clin cancer Res. 2005, 11: 3274-3279. 10.1158/1078-0432.CCR-04-2207.CrossRefPubMed
25.
Gasco M, Sullivan A, Repellin C, Brooks L, Farrell PJ, Tidy JA, et al: Coincident inactivation of 14-3-3sigma and p16INK4a is an early event in vulval squamous neoplasia. Oncogene. 2002, 21: 1876-1881. 10.1038/sj.onc.1205256.CrossRefPubMed
26.
Shepherd JH: Cervical and vulva cancer: changes in FIGO definitions of staging. Br J Obstet Gynaecol. 1996, 103: 405-406.CrossRefPubMed
27.
WHO: Pathology and Genetics Tumours of the Breast and Female Genital Organs. World Health Organization Classification of Tumors. 2003, Lyon: IARC Press, 316-321.
28.
Knopp S, Bjorge T, Nesland JM, Trope C, Scheistroen M, Holm R: p16INK4a and p21Waf1/Cip1 expression correlates with clinical outcome in vulvar carcinomas. Gynecol Oncol. 2004, 95: 37-45. 10.1016/j.ygyno.2004.07.026.CrossRefPubMed
29.
Knopp S, Bjorge T, Nesland JM, Trope C, Holm R: Cyclins D1, D3, E, and A in vulvar carcinoma patients. Gynecol Oncol. 2005, 97: 733-739. 10.1016/j.ygyno.2005.03.025.CrossRefPubMed
30.
Knopp S, Nesland JM, Trope C, Holm R: p14ARF, a prognostic predictor in HPV-negative vulvar carcinoma. Am J Clin Pathol. 2006, 126: 266-276. 10.1309/E9E8Y9WG5QE3LK29.CrossRefPubMed
31.
Scheistroen M, Trope C, Kaern J, Pettersen EO, Alfsen GC, Nesland JM: DNA ploidy and expression of p53 and C-erbB-2 in extramammary Paget's disease of the vulva. Gynecol Oncol. 1997, 64: 88-92. 10.1006/gyno.1996.4517.CrossRefPubMed
32.
Nakajima T, Shimooka H, Weixa P, Segawa A, Motegi A, Jian Z, et al: Immunohistochemical demonstration of 14-3-3 sigma protein in normal human tissues and lung cancers, and the preponderance of its strong expression in epithelial cells of squamous cell lineage. Pathol Int. 2003, 53: 353-360. 10.1046/j.1440-1827.2003.01481.x.CrossRefPubMed
33.
Kurokawa I, Mizutani H, Kusumoto K, Nishijima S, Tsujita-Kyutoku M, Shikata N, et al: Cytokeratin, filaggrin, and p63 expression in reepithelialization during human cutaneous wound healing. Wound Repair Regen. 2006, 14: 38-45. 10.1111/j.1524-475X.2005.00086.x.CrossRefPubMed
34.
Ghahary A, Marcoux Y, Karimi-Busheri F, Li Y, Tredget EE, Kilani RT, et al: Differentiated keratinocyte-releasable stratifin (14-3-3 sigma) stimulates MMP-1 expression in dermal fibroblasts. J Invest Dermatol. 2005, 124: 170-177. 10.1111/j.0022-202X.2004.23521.x.CrossRefPubMed
35.
Mhawech P, Greloz V, Assaly M, Herrmann F: Immunohistochemical expression of 14-3-3 sigma protein in human urological and gynecological tumors using a multi-tumor microarray analysis. Pathol Int. 2005, 55: 77-82. 10.1111/j.1440-1827.2004.01797.x.CrossRefPubMed
36.
Bhatia K, Siraj AK, Hussain A, Bu R, Gutierrez MI: The tumor suppressor gene 14-3-3 sigma is commonly methylated in normal and malignant lymphoid cells. Cancer Epidemiol Biomarkers Prev. 2003, 12: 165-169.PubMed
37.
38.
van Hemert MJ, Niemantsverdriet M, Schmidt T, Backendorf C, Spaink HP: Isoform-specific differences in rapid nucleocytoplasmic shuttling cause distinct subcellular distributions of 14-3-3 sigma and 14-3-3 zeta. J Cell Sci. 2004, 117: 1411-1420. 10.1242/jcs.00990.CrossRefPubMed
39.
40.
Tanaka K, Hatada T, Kobayashi M, Mohri Y, Tonouchi H, Miki C, et al: The clinical implication of 14-3-3 sigma expression in primary gastrointestinal malignancy. Int J Oncol. 2004, 25: 1591-1597.PubMed
41.
Akahira J, Sugihashi Y, Suzuki T, Ito K, Niikura H, Moriya T, et al: Decreased expression of 14-3-3 sigma is associated with advanced disease in human epithelial ovarian cancer: its correlation with aberrant DNA methylation. Clin cancer Res. 2004, 10: 2687-2693. 10.1158/1078-0432.CCR-03-0510.CrossRefPubMed
42.
Sano T, Shimooka H, Weixa P, Segawa A, Jian Z, Motegi A, et al: Immunohistochemical expression of 14-3-3 sigma protein in various histological subtypes of uterine cervical cancers. Pathol Int. 2004, 54: 743-750. 10.1111/j.1440-1827.2004.01747.x.CrossRefPubMed
43.
Audic Y, Hartley RS: Post-transcriptional regulation in cancer. Biol Cell. 2004, 96: 479-498. 10.1016/j.biolcel.2004.05.002.CrossRefPubMed
Metadata
Title
The clinicopathological and prognostic impact of 14-3-3 sigma expression on vulvar squamous cell carcinomas
Authors
Zhihui Wang
Claes G Tropè
Zhenhe Suo
Gunhild Trøen
Guanrui Yang
Jahn M Nesland
Ruth Holm
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-8-308

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