Dataset Information

The prognostic value of 14-3-3 isoforms in vulvar squamous cell carcinoma cases: 14-3-3? and ? are independent prognostic factors for these tumors.

ABSTRACT:

Background

The 14-3-3 family is comprised of highly conserved proteins that are functionally important in the maintenance of homeostasis. Their involvement with the cell cycle, their association with proto-oncogenes and oncogenes, and their abnormal expression in various tumors has linked this family of proteins to the etiology of human cancer. Mounting evidence now indicates that 14-3-3? is a cancer suppressor gene but the roles of the other 14-3-3 isoforms and their interactions in tumorigenesis have not yet been elucidated. In our current study, we examined the expression of 14-3-3?, ?, ?, ?, ? and ? in a large series of vulvar squamous cell carcinomas to evaluate any clinical significance.

Methods

Tumor biopsies from 298 vulvar carcinomas were examined by immunohistochemistry for the expression of 14-3-3?, ?, ?, ?, ? and ?. Statistical analyses were employed to validate any associations between the expression of any 14-3-3 isoform and clinicopathologic variables for this disease.

Results

High cytoplasmic levels of 14-3-3?, ?, ?, ? and ? were observed in 79%, 58%, 50%, 86% and 54% of the vulvar carcinomas analyzed, respectively, whereas a low nuclear expression of 14-3-3? was present in 80% of these cases. The elevated cytoplasmic expression of 14-3-3?, ?, ?, ? and ? was further found to be associated with advanced disease and aggressive features of these cancers. The overexpression of cytoplasmic 14-3-3? and ? significantly correlated with a poor disease-specific survival by univariate analysis (P?=?0.007 and P?=?0.04, respectively). The independent prognostic significance of these factors was confirmed by multivariate analysis (P?=?0.007 and P?=?0.009, respectively).

Conclusions

We reveal for the first time that the 14-3-3?, ?, ?, ?, ? and ? isoforms may be involved in the progression of vulvar carcinomas. Furthermore, our analyses show that high cytoplasmic levels of 14-3-3? and ? independently correlate with poor disease-specific survival.

SUBMITTER: Wang Z

PROVIDER: S-EPMC3174199 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Publications

The prognostic value of 14-3-3 isoforms in vulvar squamous cell carcinoma cases: 14-3-3β and ε are independent prognostic factors for these tumors.

Wang Zhihui Z Nesland Jahn M JM Suo Zhenhe Z Trope Claes G CG Holm Ruth R

PloS one 20110915 9

<h4>Background</h4>The 14-3-3 family is comprised of highly conserved proteins that are functionally important in the maintenance of homeostasis. Their involvement with the cell cycle, their association with proto-oncogenes and oncogenes, and their abnormal expression in various tumors has linked this family of proteins to the etiology of human cancer. Mounting evidence now indicates that 14-3-3σ is a cancer suppressor gene but the roles of the other 14-3-3 isoforms and their interactions in tum ...[more]

PMID: 21935479

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Project description:The study's aim was to investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC). A series of 101 patients surgically treated at our center from 2016 to 2020 were retrospectively enrolled: 53 node-negative (Group A) and 48 node-positive (Group B). A total of 146 samples, 101 from primary tumor (T) and 45 from nodal metastases (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF, and CD31. The reactions were evaluated on qualitative and semi-quantitative scales. Generalized Linear Model (GLM) and cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N. In Group A: p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs. 6.2%, p = 0.04). In Group B: PD-L1 positivity and high EGFR expression were found, respectively, in 77.1% and 97.9% patients (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups: tumoral immune infiltration (CD3 expression) was mainly moderate/intense (80% vs. 95%); VEGF showed strong/moderate-diffuse expression in 13.9% of T samples; CD31, related to tumoral microvessel density (MVD), showed no difference between groups; a mutated p53 and over-expressed PD-L1 showed significant association with nodal metastasis, with Odds Ratios (OR) of 4.26 (CI 95% = 1.14-15.87, p = 0.03) and 2.68 (CI 95% = 1.0-7.19, p < 0.05), respectively; since all mismatch repair proteins (MMR) showed a retained expression and ER, PR, and HER2/neu were negative, they were excluded from further analysis. The cluster analysis identified three and four sub-groups of molecular profiles, respectively, in Group A and B, with no difference in prognosis. The molecular signature of each N and corresponding T diverged significantly in 18/41 (43.9%) cases. Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expression.