Abstract
BackgroundRegional lymph node (LN) status is a well-known prognostic factor for vulvar carcinoma (VC) patients. Although the reliable LN assessment in VC is crucial, it presents significant diagnostic problems. We aimed to identify specific mRNA markers of VC dissemination in the LN and to address the feasibility of predicting the risk of nodal recurrence by the patterns of gene expression.MethodsSentinel and inguinal LN samples from 20 patients who had undergone surgery for stage T1-3, N0-2, M0 primary vulvar squamous cell carcinoma were analyzed. Gene expression profiles were assessed in four metastatic [LN(+)] and four histologically negative [LN(−)] lymph node samples obtained from four VC patients, by the Affymetrix U133 Plus 2.0 gene expression microarrays. Of the set of genes of the highest expression in the metastatic LNs compared to LN(−), seven candidate marker genes were selected: PERP, S100A8, FABP5, SFN, CA12, JUP and CSTA, and the expression levels of these genes were further analyzed by the real-time reverse transcription polymerase chain reaction (qRT-PCR) in 71 LN samples.ResultsAll of the seven genes in question were significantly increased in LN(+) compared to LN(−) samples. In the initial validation of the seven putative markers of metastatic LN, the Cox proportional hazard model pointed to SFN, CA12 and JUP expression to significantly relate to the time to groin recurrence in VC patients.ConclusionsOur findings first provided evidence that SFN, CA12 and JUP have a potential of marker genes for the prediction of the groin recurrence LN in VC patients.
Highlights
Regional lymph node (LN) status is a well-known prognostic factor for vulvar carcinoma (VC) patients
To evaluate which biological processes are represented within the obtained probe set list, the differentially expressed genes were annotated with the Gene Ontology (GO) terms
Correlations between gene expression levels and time to groin recurrence in VC patients Subsequently, we examined a correlation between the expression levels of the seven selected genes and time to groin recurrence in VC patients using Cox's proportional hazard analysis
Summary
Regional lymph node (LN) status is a well-known prognostic factor for vulvar carcinoma (VC) patients. Vulvar carcinoma (VC) is a rare genital malignancy with age-standardized incidence rates (ASR) ranging worldwide between 0.5 and 1.5 per 100,000 [1]. In early stage VC patients, the probability of a positive inguinal LN finding is only 11-25% [5]. The concept of sentinel LN biopsy in early stage VC is becoming increasingly accepted while the problem of optimal treatment of patients with metastatic regional LNs is still being discussed.
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