Vimentin overexpression as a novel poor prognostic biomarker in eyelid sebaceous gland carcinoma
Mansi Bhardwaj, Seema Sen, Kunzang Chosdol, Sameer Bakhshi, Neelam Pushker, Anjana Sharma, Seema Kashyap, Mandeep S Bajaj, Vijay Kumar SinghRead More
Vimentin is an intermediate-sized filament which is highly expressed in mesenchymal cells and is associated with epithelial–mesenchymal transition (EMT). EMT markers ZEB2 and Slug lead to Vimentin overexpression and E-cadherin loss, resulting in invasion and metastasis. However, the status of Vimentin remains unexplored in eyelid sebaceous gland carcinoma (SGC). The study aims to determine status of Vimentin in SGC and its association with EMT markers E-cadherin, ZEB2 and Slug.
Methods Vimentin protein expression was undertaken in 66 cases with SGC by immunohistochemistry (IHC). Messenger RNA (mRNA) expression was determined in 42 fresh tissues by quantitative real-time PCR. Association of Vimentin with E-cadherin, ZEB2 and Slug was also analysed. Patients were followed up for 17–69 months (mean 34.02 ± 14.73 months).
Results IHC revealed Vimentin overexpression in 37/66 (56%) cases. This overexpression showed significant association with lymph node metastasis (p=0.004) and pagetoid spread (p=0.05). Patients with high Vimentin expression also had poor disease-free survival (p=0.033). Univariate Cox regression model indicated that high Vimentin expression (p=0.043) and advanced tumour stage (p=0.002) were independent adverse prognostic factors. High Vimentin mRNA expression was seen in 16/42 (38%) cases and correlated significantly with lymph node metastasis (p=0.027), advanced tumour stage (p=0.002) and large tumour size (p=0.023). Vimentin expression overall showed a significant inverse association with E-cadherin and direct association with ZEB2 expression.
Conclusions Vimentin overexpression in SGC is associated with EMT and leads to poor clinical outcome. It also emerged as a novel predictor for lymph node metastasis and poor survival.