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Open Access Research article

Estimation of groin recurrence risk in patients with squamous cell vulvar carcinoma by the assessment of marker gene expression in the lymph nodes

Magdalena Kowalewska1*, Jakub Radziszewski2, Krzysztof Goryca34, Mateusz Bujko1, Malgorzata Oczko-Wojciechowska5, Michal Jarzab5, Janusz Aleksander Siedlecki1 and Mariusz Bidzinski6

Author Affiliations

1 Department of Molecular Biology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Roentgena, 5, Warsaw 02-781, Poland

2 Department of Surgery, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Wawelska 15, Warsaw 00-973, Poland

3 Department of Oncological Genetics, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Roentgena 5, Warsaw 02-781, Poland

4 Laboratory of Bioinformatics and Systems Biology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Roentgena 5, Warsaw 02-781, Poland

5 Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Wybrzeze Armii Krajowej 15, Gliwice 44-100, Poland

6 Department of Gynecological Oncology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Roentgena, 5, Warsaw 02-781, Poland

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BMC Cancer 2012, 12:223  doi:10.1186/1471-2407-12-223

Published: 6 June 2012

Abstract

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. 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.

Methods

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

All 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.

Conclusions

Our 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.

Keywords:
Vulvar carcinoma; Lymph node; Microarray; Expression marker; Real-time RT-PCR