Epithelial–mesenchymal transition (EMT) in vulvar cancer with and without inguinal lymph node involvement

Abstract

Epithelial-mesenchymal transition (EMT) is associated with increased metastatic spread and poor prognosis. Data on vulvar carcinoma are limited. Thirty-two cases of squamous cell carcinoma of the vulva (16 with and 16 without inguinal lymph node metastases) and their lymph node deposits were evaluated for immunohistochemical expression of EMT markers (vimentin, cyclin D1, e-cadherin), p16, p53 and Ki-67. Results of EMT-immunostainings were compared to lymph node involvement and expression of p53 and p16. The micro-anatomical staining pattern for EMT markers comparing the tumor center with the front of invasion was analysed in each tumor. There was no difference in the expression of EMT markers between node negative and node positive tumors. Staining for vimentin and cyclin D1 was seen within tumor cells at the front of invasion in 100 and 84.4% of the tumors, respectively. The majority of cases (68.7%) showed negative or reduced staining for e-cadherin in this micro-anatomical localization. Tumor cells within the lymph node metastases showed positive staining for e-cadherin in 75% and for cyclin D1 in 49% of the cells but were negative for vimentin in 13 out of 16 cases (81.3%). Tumors with aberrant p53 staining represented a non-significant higher vimentin but significantly higher cyclin D1 expression at the front of invasion than those with p53 wild-type pattern. The present study shows no differences in the expression of EMT markers between node positive and node negative vulvar cancers. The evaluation of immunostaining within the micro-anatomical context indicates that an EMT-phenotype is restricted to the tumor cells at the front of invasion. Paired analyses of vulvar carcinomas and their lymph node deposits suggest mesenchymal-epithelial transition (MET) in the metastatic deposits. Immunohistochemical staining results may suggest that EMT is more prevalent in vulvar cancer with aberrant p53 staining.