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Open Access Research

Prognostic significance of c-KIT in vulvar cancer: bringing this molecular marker from bench to bedside

Beatriz de Melo Maia1*, André Mourão Lavorato-Rocha1, Iara Sant’Ana Rodrigues1, Glauco Baiocchi2, Flávia Munhoz Cestari2, Monica Maria Stiepcich3, Ludmila Thomé Domingues Chinen4, Kátia C Carvalho5, Fernando Augusto Soares1 and Rafael Malagoli Rocha1

Author Affiliations

1 Anatomic Pathology Department, Hospital AC Camargo, Rua Antônio Prudente, 109. 1o Andar–Patologia Investigativa, Liberdade, São Paulo, SP, CEP: 01509-900, Brazil

2 Gynecologic Oncology Department, Hospital AC Camargo, São Paulo, Brazil

3 Pathology Department, Fleury Institute, São Paulo, Brazil

4 Oncology Department, Hospital AC Camargo, São Paulo, Brazil

5 Obstetrics and Gynecology Department, School of Medicine of Sao Paulo University, São Paulo, Brazil

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Journal of Translational Medicine 2012, 10:150  doi:10.1186/1479-5876-10-150

Published: 28 July 2012

Abstract

Background

Vulvar carcinomas are rare tumors, and there is limited data regarding molecular alterations. To our knowledge there are no published studies on c-KIT and squamous cell carcinomas of the vulva (VSCC). Although there are a significant number of other tumor types which express c-KIT, there remains controversy as to its relationship to patient outcome. Thus, we wished to investigate such controversial findings to determine the prognostic importance of c-KIT by evaluating its protein and mRNA expression in VSCCs, correlating these findings with clinicopathological features and Human Papillomavirus (HPV) infection.

Methods

c-KIT expression was scored by immunohistochemistry (IHC) as positive or negative in 139 formalin-fixed paraffin-embedded (FFPE) cases of vulvar carcinomas arrayed in a tissue microarray (TMA) using the DAKO® A4502 rabbit polyclonal c-KIT antibody (diluted 1:100). c-KIT mRNA was evaluated by qRT-PCR in 34 frozen samples from AC Camargo Hospital Biobank (17 tumoral and 17 non-tumoral samples) using TaqMan probes–Applied Biosystems [Hs00174029_m1]. HPV genotyping was assessed in 103 samples using Linear Array® HPV Genotyping Test kit (Roche Molecular Diagnostics, Basel, Switzerland). All results obtained were correlated with clinical and pathological data of the patients.

Results

c-KIT protein was positive by immunohistochemistry in 70.5% of the cases and this was associated with a higher global survival (p = 0.007), a higher recurrence-free survival (p < 0.0001), an absence of associated lesions (p = 0.001), lymph node metastasis (p = 0.0053), and HPV infection (p = 0.034). Furthermore, c-KIT mRNA quantitation revealed higher levels of transcripts in normal samples compared to tumor samples (p = 0,0009).

Conclusions

Our findings indicate that those vulvar tumors staining positively for c-KIT present better prognosis. Thus, positivity of c-KIT as evaluated by IHC may be a good predictor for use of more conservative surgery techniques and lymph node dissection in vulvar cancer. So part of the essence of our study is to see the possibility of translating our current results from the bench to the bedside. This will help provide patients a more appropriate, less mutilating treatment, in order to keep the maximum physical and psychic quality as possible to these women.

Keywords:
Vulvar carcinoma; HPV; c-KIT; Immunohistochemistry; qRT-PCR