Immunohistochemical expression of 14‐3‐3 sigma protein in human urological and gynecological tumors using a multi‐tumor microarray analysis

Abstract

14-3-3 sigma is an exclusive epithelial marker and data on its expression in different malignancies are very scarce. The aims of the present study are to screen its expression in the most common neoplasms occurring in the urological and gynecological tract and to evaluate its use as a diagnostic marker. A tissue microarray was constructed using 350 samples from 13 different neoplasms. Immunohistochemical analysis using a polyclonal 14-3-3 sigma antibody was performed. Overall, this protein was positive in 141 and negative in 209 tumors. The most frequent expression was seen in squamous cell carcinoma of the cervix and urothelial bladder carcinoma, followed by prostatic and endometrial adenocarcinoma. 14-3-3 sigma was able to distinguish prostate adenocarcinoma from urothelial bladder carcinoma, with an odds ratio of 0.028 (P = 0.001; 95% CI, 0.0003-0.222), and distinguish seminoma from embryonal carcinoma of the testis, with an odds ratio of 0.061 (P = 0.009; 95% CI, 0.007-0.5014). It also has a good value in differentiating renal clear cell carcinoma from papillary carcinoma, with an odds ratio 0.470 (P < 0.001; 95% CI, 0.008-0.261). 14-3-3 sigma seems to have good potential use as an epithelial marker, after confirmation with further targeted studies. Finally, as with all immunohistochemical markers, we can optimize the utility of this protein to distinguish tumor mimics by including it in an appropriate immunohistochemical panel.

Expression of 14-3-3σ in cervical squamous cell carcinomas: Relationship with clinical outcome

“…Furthermore, Mhawech et al (15) identified low level of 14-3-3Û protein in 3/9 (33%) cervical SSCs, whereas, Sano et al (30) did not find low level of 14-3-3Û protein in any of the 29 cervical SSCs tested. In the present study we detected low level of 14-3-3Û in about 50% of cervical SSCs when comparing with normal cervical squamous epithelium.…”

“…In the present study we detected low level of 14-3-3Û in about 50% of cervical SSCs when comparing with normal cervical squamous epithelium. These conflicting results may be explained by the small number of cases included in the previous works (15,30), the use of different 14-3-3Û antibodies and immunohistochemical staining methods and the differences in scoring of the immunohistochemical staining. The low 14-3-3Û protein level in a relative high number of cervical SSC and the finding of no association between 14-3-3Û protein expression and FIGO stage, suggested that loss of 14-3-3Û protein expression may occur as a relatively early event in cervical tumorigenesis.…”

“…Inactivation of 14-3-3Û gene by CpG methylation and/or reduced expression of 14-3-3Û have been reported in a varity of human cancers, including ovarian (13,14), cervix (15), vulvar (16,17), corpus (18), lung (19), oral (20), liver (21), skin (22), breast (23,24), gastric (25,26), renal (27), testis (27) and colorectal (28). Association of 14-3-3Û with clinical outcome has been found in patients with endometrial carcinoma (18), ovarian carcinoma (14), breast carcinoma (24) and colorectal carcinoma (28).…”

14-3-3 proteins—an update

“…In lung cancer, one report showed that squamous cell carcinomas express 14-3-3σ more strongly than adenocarcinomas, suggesting that this protein has a tendency to be more expressed in cells with squamous differentiation [62]. As an epithelial marker, 14-3-3σ expression could distinguish prostatic adenocarcinoma from urothelial carcinoma and seminoma from embryonal carcinoma [68]. This finding may help pathologists to differentiate these tumor types.…”

The role of epigenetic inactivation of 14-3-3σ in human cancer

“…Alterations in the expression of 14-3-3σ were shown to be characteristic for distinct cell types in tumors of the same location. For example, 14-3-3σ expression was used to distinguish various types of ovarian carcinoma [35], and to discriminate between urothelial and prostate carcinoma [36].…”