Epithelial to mesenchymal transition markers are associated with an increased metastatic risk in primary cutaneous squamous cell carcinomas but are attenuated in lymph node metastases.
J Dermatol Sci
; 72(2): 93-102, 2013 Nov.
Article
in En
| MEDLINE
| ID: mdl-23928229
ABSTRACT
BACKGROUND:
Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in humans and approximately 5% metastasize, usually to regional lymph nodes. Epithelial to mesenchymal transition (EMT) is a process involving loss of intercellular adhesion, acquisition of a mesenchymal phenotype and enhanced migratory potential; epithelial markers, such as E-cadherin, are down-regulated and mesenchymal proteins (Vimentin), increased.OBJECTIVE:
To investigate the expression of EMT markers in metastatic SCC (MSCC) and their corresponding metastases, and to correlate them with clinico-pathological factors associated with an increased risk of metastasis.METHODS:
We performed a retrospective study that included 146 cSCC samples (51 primary non-metastatic, 56 primary metastatic, 39 lymphatic metastases). Immunohistochemistry for E-cadherin, Vimentin, Snail, beta-catenin, Twist, Zeb1 and Podoplanin was performed.RESULTS:
Loss of membranous E-cadherin was observed in 77% cSCCs, with no differences between MSCC and non-MSCC. Among the transcriptional factors controlling EMT, no significant Snail1 expression was detected. Twist, Zeb1, Vimentin, beta-catenin and Podoplanin were significantly overexpressed in MSCCs. Twist ectopic expression in SCC13 cells induced Zeb1, Vimentin and Podoplanin expression and E-cadherin delocalization. These changes resulted in a scattered migration pattern in vitro. Expression of EMT markers was decreased in the metastases when compared with the corresponding primary tumors.CONCLUSION:
These results suggest that a partial EMT, characterized by the expression of Twist but without a total E-cadherin depletion, is involved in the acquisition of invasive traits by cSCC, but the process is downregulated in lymph node metastases.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Skin Neoplasms
/
Carcinoma, Squamous Cell
/
Biomarkers, Tumor
/
Gene Expression Regulation, Neoplastic
/
Epithelial-Mesenchymal Transition
/
Lymphatic Metastasis
Type of study:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
J Dermatol Sci
Journal subject:
DERMATOLOGIA
Year:
2013
Document type:
Article