Expression of marker genes in the lymph nodes predicts the recurrence of squamous cell vulvar carcinoma.

BACKGROUND: Regional 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. PURPOSE: 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. EXPERIMENTAL DESIGN: Sentinel 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. RESULTS: Five of the genes, PERP, S100A8, FABP5, SFN and CA12, 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 and CA12 expression to significantly relate to the time to groin recurrence in VC patients. CONCLUSIONS: PERP, S100A8, FABP5, SFN and CA12 have a potential of marker genes for the molecular testing of LN involvement in VC patients.

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