Epithelial-to-Mesenchymal Transition in Penile Squamous Cell Carcinoma

Masferrer, Emili; Ferrándiz-Pulido, Carla; Masferrer-Niubò, Magalí; Rodríguez-Rodríguez, Alfredo; Gil, Inmaculada; Pont, Antoni; Servitje, O.; Herreros, Antonio Garcı́a de; Lloveras, Belén; García-Patos, Vicenç; Toll, Agustí; Hernández-Muñoz, Inmaculada

doi:10.1016/j.juro.2014.07.083

Cited by 12 publications

(12 citation statements)

References 27 publications

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“…The effects of LAMC2 on PSCC cells may partially result from LAMC2directed EMT in PSCC cells; this hypothesis is supported by previous reports showing that EMT endows cells with migratory and invasive properties. 23 Elevated levels of both tLAMC2 and sLAMC2 were significantly associated with shorter DSS in PSCC patients; however, N stage, pathologic grade, and sLAMC2, but not tLAMC2, SCC-Ag, or CRP, were independent prognostic factors according to the multivariate regression analysis in our study. These results may be in accordance with the lower HRs for tLAMC2, SCC-Ag, or CRP compared to those for N stage, pathologic grade, and sLAMC2 (Table S4).…”

Section: Discussioncontrasting

confidence: 57%

“…According to the definitions used in previous reports, a high level of LAMC2 expression in tumor tissues (tLAMC2) was defined as more than 30% of the tumor cells staining positive for LAMC2, 17,22 while a low level of E-cadherin expression was defined as less than 90% of the tumor cells staining positive for E-cadherin. 23…”

Section: Immunohistochemistry (Ihc) Assaysmentioning

confidence: 99%

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Elevated serum LAMC2 is associated with lymph node metastasis and predicts poor prognosis in penile squamous cell carcinoma

Zhou

Deng

Chen

et al. 2018

CMAR

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PurposeMolecular biomarkers, especially serologic factors, have been widely applied in cancer diagnosis and patient follow-up. However, there are few valuable prognostic factors in penile squamous cell carcinoma (PSCC). Here, the authors investigated whether laminin gamma 2 (LAMC2) expression, especially serum LAMC2 (sLAMC2) level, was a suitable prognostic factor that could aid in the prediction of survival in PSCC.Patients and methodsThis study included 114 PSCC patients. Reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect LAMC2 expression; enzyme-linked immunosorbent assays were used to test sLAMC2 concentration; and a Transwell assay and an in vivo experiment in nude mice were used to test PSCC cell migration, invasion, and metastasis. The chi-squared test was used to analyze the association between LAMC2 level and clinical parameters, the Cox proportional hazards regression model was used to evaluate the hazard ratio for death, and Kaplan–Meier analysis with a log-rank test was used for the survival analysis.ResultsLAMC2 was overexpressed in PSCC tissues, and the LAMC2 expression level was higher in metastatic lymph node (LN) tissues than in primary cancer tissues; moreover, the LAMC2 levels in primary cancer tissues and sLAMC2 were higher in patients with LN metastasis than in those without LN metastasis. Upregulated LAMC2 facilitated the migration, invasion, and epithelial-to-mesenchymal transition of PSCC cells in vitro and promoted LN metastasis of PSCC cells in nude mice. Elevated LAMC2 levels were strongly correlated with advanced clinicopathologic parameters, especially LN metastasis, in PSCC patients and predicted shorter disease-specific survival. The predictive value of sLAMC2 is superior to that of C-reactive protein and squamous cell carcinoma antigen previously reported in PSCC patients, and a stratification analysis revealed that the level of sLAMC2 had a higher predictive value for disease-specific survival in early penile cancer (especially at the N0/X stage) than in later-stage penile cancer.ConclusionThese findings suggest that sLAMC2 is a potential serologic prognostic marker in PSCC and could aid in risk stratification in early-stage PSCC patients.

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Section: Discussioncontrasting

confidence: 57%

Section: Immunohistochemistry (Ihc) Assaysmentioning

confidence: 99%

Elevated serum LAMC2 is associated with lymph node metastasis and predicts poor prognosis in penile squamous cell carcinoma

Zhou

Deng

Chen

et al. 2018

CMAR

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“…In contrast, it is more common in developing countries accounting for up to 10-17% of cancer in males with an incidence that reaches 4 per 100,000 [1,2]. Squamous cell carcinoma (SCC) is the predominant cancer type and accounts for over 95% of penile cancer cases [3][4][5]. The main treatment for advanced tumors is phalectomy and, when inguinal lymph node metastasis is present, bilateral inguinal lymphadenectomy is also performed.…”

Section: Introductionmentioning

confidence: 99%

Molecular carcinogenesis in equine penile cancer: A potential animal model for human penile cancer

Suárez‐Bonnet

Willis

Pittaway

et al. 2018

Urologic Oncology: Seminars and Original Investigations

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“…For this reason, we analyzed the levels of expression of STAT3 Y705. We [93,94], cervical [22] and penile carcinomas [95].…”

Section: Histopathological Analysismentioning

confidence: 90%

First Evidences of Epithelial-Mesenchymal Transition and Cancer Stem-Cell Phenotype Acquisition in Dermo-Epidermal Junction of BPV-Infected Neoplasms

Araldi

Oliveira

Mattoso

et al. 2017

JBBS

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Introduction: Bovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis, infectious and neoplastic disease, characterized by the presence of multiple papillomas that can regress spontaneously or to persist and progress to malignancies when in association with environmental cofactors. Although recognized that the BPV can induce DNA damages, the viral role following cancer initiation remains unresolved. Based on this, we stablished cell lines derived from cutaneous papilloma, fibropapilloma and esophageal carcinoma to study the BPV action on epithelial-mesenchymal transition (EMT). Our results showed strong evidences that the virus action can contribute to EMT and, therefore, metastasis. Aim: In this study, we analyzed the expression levels of the EMT markers (cytokeratin 10, STAT3 Y705, Oct-3/4 and vimentin) in paraffin-embed samples, using the same tissues that originated the cell lines previous studied, aiming to validate the results observed using cell lines. Material and Methods: Expression levels of these markers was analyzed by immunohistochemistry and the collagen composision by Picrosirius red staining. Results: We verified an overexpression of these markers in fibroblastoid cells present into the epidermis and ketarinocyte-like cells into the dermis present in dermo-epidermal junction. These data reinforce our previous results using cell cultures, validating both systems (cell culture and paraffin-embed tissues) as useful models to study the natural history of BPV-infected lesions. Conclusion: Altogether, the results from these systems indicate that the BPV promote the cancer progression and metastasis through the transdifferentiation of an epithelial to mesenchymal cells (EMT).

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Epithelial-to-Mesenchymal Transition in Penile Squamous Cell Carcinoma

Abstract: Our findings indicate that in penile squamous cell carcinoma epithelial-to-mesenchymal transition is associated with poor prognosis but not with the presence of HPV.

Cited by 12 publications

References 27 publications

Elevated serum LAMC2 is associated with lymph node metastasis and predicts poor prognosis in penile squamous cell carcinoma

Elevated serum LAMC2 is associated with lymph node metastasis and predicts poor prognosis in penile squamous cell carcinoma

Molecular carcinogenesis in equine penile cancer: A potential animal model for human penile cancer

First Evidences of Epithelial-Mesenchymal Transition and Cancer Stem-Cell Phenotype Acquisition in Dermo-Epidermal Junction of BPV-Infected Neoplasms

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