However, we found that high expression of 14-3-3 in cytoplasm as well as in nucleus was significantly correlated to large tumor diameter and deep of invasion. 14-3-3 protein expression was found in 72%, 59% and 75% of the carcinomas, respectively, and low levels in 28%, 41% Rabbit Polyclonal to Akt (phospho-Tyr326) and 25% of the cases, respectively. High level of 14-3-3 in cytoplasm, nucleus and cytoplasm/nucleus was significantly correlated to large tumor diameter (p= 0.001,p= 0.002 andp= 0.001, respectively) and deep invasion (p= 0.01,p= 0.001 andp= 0.007, respectively). Variations of 14-3-3 protein expression were not associated to disease-specific survival. == Conclusion == Our results indicate that 14-3-3 may be involved in the development of a subset of vulvar squamous cell carcinomas by down-regulation of 14-3-3 protein. Neither cytoplasmic nor nuclear level of 14-3-3 expression was associated with prognosis. == Background == Vulvar carcinoma represents 35% of all female genital cancer [1] and was previously considered a disease of elderly women. However, we see an increase in the incidence of vulvar carcinomas among younger women in recent years [2]. Considerable morbidity is often followed radical surgery, which has been the standard treatment [3]. Individualized therapy has been introduced to raise the quality of life for vulvar cancer patients SJA6017 [4]. Targeted therapy urge us to search for factors involved in tumorigenesis as well as identification of new tumor markers for therapy. In mammals, 14-3-3 proteins are composed of a highly conserved multigene family of small acidic proteins, including seven 14-3-3 isoforms (, , , , , , ) [5]. As a phosphoserine/phosphothreonine-binding protein, 14-3-3s bind to proteins within their RSXpSXP and RX(Y/F)XpSXP sequences (pS represents phosphoserine or phosphothreonine) [6] and thereby play an important role in various cellular processes such as altering enzymatic activity, subcellular localization, protein-protein interactions, dephosphorylation, and proteolysis of individual target proteins [7-9]. 14-3-3, also named stratiffin, is mostly expressed SJA6017 in human epithelial cells [8]. Responsive to DNA damage, 14-3-3 expression is induced in a p53-dependent manner [10-12]. SJA6017 14-3-3 sequesters cyclin B1-CDC2 complex in cytoplasm, and prevents its entry into nucleus resulting in G2/M cell cycle arrest [10,12]. Furthermore, 14-3-3 can link to CDK2 and CDK4 and block the cell cycle entry [13]. Thus, 14-3-3 acts as a negative regulator of cell cycle progression and is linked to cancer [14]. Epigenetic change in the 14-3-3 gene by CpG hypermethylation followed by down-regulation of 14-3-3 expression has been demonstrated in various carcinomas [15-22]. Furthermore, in breast carcinoma [22], endometrial carcinoma [23] and colorectal carcinoma [24] 14-3-3 expression was found to be associated with the patients’ clinical outcome. In a previous study, including a limited number of vulvar carcinomas, appropriately 60% of the cases revealed CpG methylation in the 14-3-3 gene [25]. However, the expression of the 14-3-3 protein and its connection with prognosis has still not been reported in vulvar carcinoma patients. Thus, we intended to study the 14-3-3 expression in a series of 302 vulvar squamous cell carcinomas in order to disclose the correlation between 14-3-3 expression and its prognostic value. == Methods == == Patient materials == A retrospective study was performed, in which 302 patients with squamous cell carcinoma of vulvar underwent surgery at The Norwegian Radium Hospital in the period 19772006. Before surgery, radiotherapy was given to 9 (3%) of the patients, additionally, 3 (1%) of the patients received chemotherapy. Radical vulvectomy was performed on 201 (67%) of the patients. Postoperative irradiation was given to 63 (21%), chemotherapy to 3 (1%) and irradiation/chemotherapy to 4 (1%) of the patients. One hundred and eight (36%) patients suffered from a relapse. The median age at diagnosis was 74 years (range 3596 years). All patients were followed until death or 31. December, 2006. One hundred and twenty patients (40%) died of vulvar cancer. The median follow-up time for all patients was 52 months (range 0.4346 months), whereas the median follow-up time for patients alive at last observation was 131 months (range 11346 months). All tumors were staged according.