Estimation of groin recurrence risk in patients with squamous cell vulvar carcinoma by the assessment of marker gene expression in the lymph nodes.
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 T(1-3), N(0-2), M(0) 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.
Department of Molecular Biology, Maria Sklodowska-Curie Memorial Cancer Centre, Warsaw, Poland. magdak@coi.waw.pl
Magdalena
M
Kowalewska
Jakub
J
Radziszewski
Krzysztof
K
Goryca
Mateusz
M
Bujko
Malgorzata
M
Oczko-Wojciechowska
Michal
M
Jarzab
Janusz Aleksander
JA
Siedlecki
Mariusz
M
Bidzinski
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006119:Groin; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000235:genetics; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D012008:Recurrence; D015203:Reproducibility of Results; D014846:Vulvar Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*
D014408:Biomarkers, Tumor