Flavia Persechino

Dottoressa di ricerca

ciclo: XXXII



Titolo della tesi: FGFR expression profile, keratinocyte proliferation/differentiation markers and EMT-related genes in AK: a possible predictive factor for AK malignant progression

Actinic Keratosis (AK) is the UV-induced preneoplastic skin lesion which has been clinically classified in keratinocytic intraepithelial neoplasia (KIN) of ‘low’(KIN I), ‘intermediate’ (KIN II) and ‘high’(KIN III) grade. During KIN progression, the downregulation of several keratinocyte differentiation markers has been observed (Lambert et al., 2014), while the epithelial-mesenchymal transition (EMT) phenotype it has been recently described as a typical feature of some aggressive SCCs that directly develop from KIN I through the so-called differentiated pathway. More recently, the presentation of the FGF1 and FGF2 inhibitor (Dobesilate) as a new, effective therapeutic strategy strongly suggested that the deregulation of FGF/FGFR axis could contribute to AK pathogenesis . In this regard, our recent findings underlining that the altered FGFR2 splicing and the consequent aberrant expression of the mesenchymal FGFR2c variant in epithelial context induce impairment of differentiation and EMT induction, strongly encouraged us to investigate if the FGFR2 isoform switch could also take place in AK-keratinocytes possibly contributing the rapid progression of KIN I toward aggressive SCCs. The detailed molecular analysis performed in this work, have first highlighted that the early differentiation markers K1 and DSG1 appeared progressively downregulated during KIN progression, while the downmodulation of the terminal differentiation marker FIL was particularly marked just in some of the KIN I lesions suggesting that FIL could be one of the markers for that KIN I lesions destined to a rapid malignant progression toward SCC. In contrast, a modulation of epithelial/mesenchymal markers and an induction of the transcription factors Snail1 and ZEB1, compatible with pathological EMT, were detectable in all the analyzed AK samples, without significant correlation with KIN progression. Regarding FGFR expression, we found that a modulation of FGFR2b/FGFR2c isoforms, compatible with an FGFR2 isoform switch, as well as the upregulation of FGFR4, are detectable starting from KIN I lesions, encouraging us to suppose that they could be key events detectable starting from the early steps of AK pathogenesis. In contrast, the expression of FGFR3c was detected mainly in KIN II and KIN III lesions, suggesting that the appearance of this receptor could be a late event in AK progression. Finally, the increased expression of FGF2 mRNA in the dermal portion of all KIN lesions further supported the idea that aberrant epidermal/dermal paracrine loops based on FGF2/FGFR axis could contribute to AK pathogenesis. It is worth to note that, particularly in one of the KIN I samples a strong induction of Snail1, as well as an upregulation of FGFR2c, FGFR4, and FGF2 was observed, encouraging us to further assess if these proteins could be specific molecular markers, whose expression profile could in future help to quickly intercept KIN I lesion destined to a rapid, direct progression toward SCC. In the second part of this workwe pointed on the identification pof the specific signaling pathways downstream FGFR2c responsible for its oncogenic outcome in epithelial context. addressing particular attention on PKCe, whose overexpression alone was sufficient to induce an EMT-related phenotype in epithelial cells. Our results showed that aberrant expression and signaling of FGFR2c, but not those of FGFR2b, in human keratinocytes induced a strong phosphorylation/activation of PKCε. The use of siRNA approach showed that PKCε is the hub signaling downstream FGFR2c responsible for the modulation of EMT markers and for the induction of the EMT-related transcription factors STAT3, Snail1 and FRA1, as well as for the acquisition of the invasive behavior. Moreover, the depletion of ESRP1, responsible for FGFR2 splicing in epithelial cells, indicated that the activation of PKCε is the key molecular event triggered by FGFR2 isoform switch and underlying EMT induction. Therefore, the expression/activation of PKCε could represent an additional marker useful to identify that KIN I lesion destined to a rapid progression toward SCC. Our results represent the first step to advance the understanding of the molecular bases of FGFR signaling deregulation occurring in epithelial tissues from the physiological oncosoppressive to the pathological pre-neoplastic and finally oncogenic profiles.

Produzione scientifica

  • 11573/1483552 - 2016 - Un caso di forma eruttiva di nevi di Spitz (04f Poster)
    PERSECHINO, FLAVIA; PELLACANI, GIOVANNI
  • 11573/1483547 - 2015 - BRAFV600E mutated and wild type melanomas: dermoscopy and reflectance confocal microscopy characterization (04f Poster)
    PERSECHINO, FLAVIA; PELLACANI, GIOVANNI
  • 11573/883970 - 2016 - A case of Koebner phenomenon in a patient with tattoo to lips. (01a Articolo in rivista)
    TAMMARO, ANTONELLA; ROMANO, IRENE; PERSECHINO, FLAVIA; PERSECHINO, SEVERINO
  • 11573/987085 - 2017 - Successful of subcutaneous and oral hyposensitizing therapy in 30 patients (01a Articolo in rivista)
    TAMMARO, ANTONELLA; DE MARCO, GABRIELLA; PERSECHINO, FLAVIA; PERSECHINO, SEVERINO
  • 11573/883969 - 2016 - Heavy metal and tattoo: an allergy and legislative problem. (01a Articolo in rivista)
    TAMMARO, ANTONELLA; CORTESI, GIORGIA; PIGLIACELLI, FLAVIA; PERSECHINO, FLAVIA; DE MARCO, GABRIELLA; PERSECHINO, SEVERINO
  • 11573/883968 - 2016 - Effects of TIO NICKEL in patients with ACD and SNAS: experience on 700 patients in Italy. (01a Articolo in rivista)
    TAMMARO, ANTONELLA; ROMANO, IRENE; DE MARCO, GABRIELLA; PIGLIACELLI, FLAVIA; D'ARINO, ANDREA; PERSECHINO, FLAVIA; PERSECHINO, SEVERINO
  • 11573/883973 - 2016 - Sea Anemone: A Rare Case of Contact Dermatitis in Italy. (01a Articolo in rivista)
    TAMMARO, ANTONELLA; PIGLIACELLI, FLAVIA; D'ARINO, ANDREA; PERSECHINO, FLAVIA; PERSECHINO, SEVERINO
  • 11573/517375 - 2013 - SUN: FRIEND OR ENEMY? (01a Articolo in rivista)
    MIRAGLIA, EMANUELE; PERSECHINO, FLAVIA; CALVIERI, STEFANO; GIUSTINI, SANDRA
  • 11573/1191258 - 2018 - Melanoma and hemangioma: An atypical presentation (01i Case report)
    PERSECHINO, SEVERINO; PIGLIACELLI, FLAVIA; PERSECHINO, FLAVIA; TAMMARO, ANTONELLA
  • 11573/1191247 - 2018 - Treatment of chronic infected post-oncological wounds with a dermal matrix: Two case studies (01i Case report)
    PERSECHINO, FLAVIA; MAGNONI, CRISTINA
  • 11573/1191253 - 2018 - Identifying the factors that influence surgeon's compliance with excisional margins of non-melanoma skin cancer (01a Articolo in rivista)
    MANNOCCI, ALICE; PERSECHINO, FLAVIA; MAGNONI, CRISTINA
  • 11573/507163 - in press - A NEW THERAPEUTIC OPTION with natural cellulose powder FOR THE TREATMENT OF SEASONAL ALLERGIC RHINITIS (01a Articolo in rivista)
    TAMMARO, ANTONELLA; NARCISI, ALESSANDRA; PERSECHINO, FLAVIA; PERSECHINO, SEVERINO
  • 11573/1080574 - 2018 - Seborrheic keratoses mimicking melanoma unveiled by in vivo reflectance confocal microscopy (01a Articolo in rivista)
    PERSECHINO, FLAVIA; PERSECHINO, SEVERINO; PELLACANI, GIOVANNI
  • 11573/380950 - 2011 - Erythema dyschromicum perstans in phototype II women: three unusual clinical cases studied with electron microscopy (01a Articolo in rivista)
    PERSECHINO, SEVERINO; PERSECHINO, FLAVIA; RAFFA, SALVATORE; TAMMARO, ANTONELLA; TORRISI, MARIA ROSARIA
  • 11573/227832 - 2009 - Carcinoma en cuirasse of the breast (01a Articolo in rivista)
    CARLESIMO, MARTA; ROSSI, ALFREDO; DE MARCO, GABRIELLA; NARCISI, ALESSANDRA; PERSECHINO, FLAVIA
  • 11573/434581 - 2012 - EFFECTS OF ORAL HYPOSENSITIZATION THERAPY WITH NICKEL ON HAEMOGLOBIN AND HAEMATOCRIT VALUES IN SENSITIZED PATIENTS (01a Articolo in rivista)
    TAMMARO, ANTONELLA; NARCISI, ALESSANDRA; ABRUZZESE, CLAUDIA; PERSECHINO, FLAVIA; PERSECHINO, SEVERINO
  • 11573/511670 - 2013 - KYRLE'S DISEASE: TREATMENT WITH MINOCYCLINE AND TOPIC TACALCITOL (01a Articolo in rivista)
    CORTESI, GIORGIA; PERSECHINO, FLAVIA; TAMMARO, ANTONELLA; PERSECHINO, SEVERINO
  • 11573/764380 - 2014 - Condyloma acuminata and mollusca contagiosa: a giant manifestation in a patient with lupus. (01a Articolo in rivista)
    PERSECHINO, SEVERINO; ABRUZZESE, CLAUDIA; PERSECHINO, FLAVIA; TAMMARO, ANTONELLA
  • 11573/438549 - 2011 - ANETODERMA: EVIDENCE OF THE RELATIONSHIP WITH AUTOIMMUNE DISEASE AND A POSSIBLE ROLE OF MACROPHAGES IN THE ETIOPATHOGENESIS (01a Articolo in rivista)
    PERSECHINO, SEVERINO; PERSECHINO, FLAVIA; RAFFA, SALVATORE; TAMMARO, ANTONELLA; TORRISI, MARIA ROSARIA
  • 11573/461343 - 2012 - TWO CASES OF CERCARIAL DERMATITIS IN AN ITALIAN LAKE (01a Articolo in rivista)
    TAMMARO, ANTONELLA; NARCISI, ALESSANDRA; PERSECHINO, FLAVIA; PERSECHINO, SEVERINO
  • 11573/596632 - 2014 - Chemotherapic outcomes in a child with neurofibromatosis type 1 and optic pathway glioma. (01a Articolo in rivista)
    GIUSTINI, SANDRA; VISCONTI, BIANCA; MIRAGLIA, EMANUELE; PERSECHINO, FLAVIA; CALVIERI, STEFANO
  • 11573/565341 - 2014 - A rare association between neurofibromatosis type 1 and vulvar sarcoma. (01a Articolo in rivista)
    MIRAGLIA, EMANUELE; PECORELLA, IRENE; PERSECHINO, FLAVIA; VISCONTI, BIANCA; CALVIERI, STEFANO; GIUSTINI, SANDRA
  • 11573/456472 - 2011 - Giant basal cell carcinoma: An old but effective therapy with 5FU (01a Articolo in rivista)
    PERSECHINO, SEVERINO; PERSECHINO, FLAVIA; TAMMARO, ANTONELLA
  • 11573/434569 - in press - CONTACT ALLERGY TO LIMONENE FROM A HOME-MADE COSMETIC (01a Articolo in rivista)
    TAMMARO, ANTONELLA; NARCISI, ALESSANDRA; DE MARCO, GABRIELLA; PERSECHINO, FLAVIA; PERSECHINO, SEVERINO
  • 11573/482222 - 2012 - Disperse yellow dye: An emerging professional sensitizer in contact allergy dermatitis (01a Articolo in rivista)
    TAMMARO, ANTONELLA; ABRUZZESE, CLAUDIA; NARCISI, ALESSANDRA; CORTESI, GIORGIA; GRIPPAUDO, FRANCESCA ROMANA; PERSECHINO, FLAVIA; PERSECHINO, SEVERINO
  • 11573/29418 - 2011 - Expression and signaling of the tyrosine kinase FGFR2b/KGFR regulates phagocytosis and melanosome uptake in human keratinocytes (01a Articolo in rivista)
    BELLEUDI, FRANCESCA; PURPURA, VALERIA; SCROFANI, CRISTINA; PERSECHINO, FLAVIA; LEONE, LAURA; TORRISI, MARIA ROSARIA
  • 11573/1191271 - 2018 - Dermoscopy of syringocystadenoma papilliferum (01i Case report)
    PERSECHINO, FLAVIA
  • 11573/1191263 - 2018 - Improving mandibular contour: A pilot study for indication of PPLA traction thread use (01a Articolo in rivista)
    PERSECHINO, FLAVIA
  • 11573/1191267 - 2018 - Folliculotropism in pigmented facial macules: Differential diagnosis with reflectance confocal microscopy (01a Articolo in rivista)
    PERSECHINO, FLAVIA
  • 11573/1191284 - 2017 - Acral melanoma (01i Case report)
    PERSECHINO, FLAVIA
  • 11573/1191251 - 2018 - Resurfacing with Ablation of Periorbital Skin Technique: Indications, Efficacy, Safety, and 3D Assessment from a Pilot Study (01a Articolo in rivista)
    PERSECHINO, FLAVIA; GIANNETTI, LUCA; D'ALESSANDRO, GIOVANNI
  • 11573/1338276 - 2020 - Dermoscopy and confocal microscopy for different chemotherapy-induced alopecia (CIA) phases characterization: preliminary study (01a Articolo in rivista)
    GARELLI, VALENTINA; PERSECHINO, FLAVIA; SPERDUTI, ISABELLA; CARO, GEMMA; ROSSI, ALFREDO
  • 11573/1333844 - 2021 - Enlarging melanocytic lesions with peripheral globular pattern: a dermoscopy and confocal microscopy study (01a Articolo in rivista)
    PERSECHINO, FLAVIA; PAOLINO, GIOVANNI; FRANCESCHINI, CHIARA; FERRARI, ANGELA; CALVIERI, STEFANO
  • 11573/1360950 - 2020 - ACANTHOSIS NIGRICANS: THE TELLTALE SIGN OF A GASTRIC CANCER RECURRENCE (01h Abstract in rivista)
    CROVETTO, ANNA; ANTOLINO, LAURA; MOSCHETTA, GIOVANNI; PERSECHINO, FLAVIA; PERSECHINO, SEVERINO; NIGRI, GIUSEPPE; VALABREGA, STEFANO; AURELLO, PAOLO; D'ANGELO, FRANCESCO; RAMACCIATO, GIOVANNI
  • 11573/1402684 - 2020 - Role of PKCε in the epithelial-mesenchymal transition induced by FGFR2 isoform switch (01a Articolo in rivista)
    RANIERI, DANILO; NANNI, MONICA; PERSECHINO, FLAVIA; TORRISI, MARIA ROSARIA; BELLEUDI, FRANCESCA
  • 11573/1396073 - 2020 - Remission of Kimura disease with carotid hypervascularization after cyclosporine treatment (01a Articolo in rivista)
    PERSECHINO, SEVERINO; BARTOLAZZI, ARMANDO; PERSECHINO, FLAVIA; TAMMARO, ANTONELLA; VALENTE, SABATINO; RAFFA, SALVATORE; VISCO, VINCENZO; TORRISI, MARIA ROSARIA
  • 11573/1462399 - 2020 - Clinical management of very small pigmented lesions. Improved clinical outcome through dermoscopy and reflectance confocal microscopy combination (01a Articolo in rivista)
    PERSECHINO, FLAVIA
  • 11573/1482859 - 2018 - Presentazione dermoscopica atipica di lesioni non melanocitarie benigne: quale aiuto dal confocale? (04f Poster)
    PERSECHINO, FLAVIA; PERSECHINO, SEVERINO; PELLACANI, GIOVANNI
  • 11573/1483593 - 2016 - Caractéristiques dermoscopiques et en microscopie confocale par réflectance dgune kératose séborrhéique clonale [Dermoscopic and reflectance confocal microscopic features of clonal seborrhoeic keratosis] (01a Articolo in rivista)
    PERSECHINO, FLAVIA; PELLACANI, GIOVANNI
  • 11573/1483639 - 2016 - Congenital glioblastoma multiforme and eruptive disseminated spitz nevi (01i Case report)
    PERSECHINO, FLAVIA; PELLACANI, GIOVANNI
  • 11573/1307854 - 2019 - The aberrant expression of the mesenchymal variant of FGFR2 in the epithelial context inhibits autophagy (01a Articolo in rivista)
    NANNI, MONICA; RANIERI, DANILO; PERSECHINO, FLAVIA; TORRISI, MARIA ROSARIA; BELLEUDI, FRANCESCA
  • 11573/1139294 - 2019 - A new high-throughput method to make a quality control on tattoo inks (01a Articolo in rivista)
    PERSECHINO, SEVERINO; TONIOLO, CHIARA; CICCOLA, ALESSANDRO; SERAFINI, ILARIA; TAMMARO, ANTONELLA; POSTORINO, PAOLO; PERSECHINO, FLAVIA; SERAFINI, MAURO
  • 11573/1560791 - 2021 - Alopecia areata in a COVID-19 patient. A case report (01f Lettera, Nota)
    CAPALBO, ALESSANDRO; GIORDANO, DOMENICO; GAGLIOSTRO, NAZARENO; BALAMPANOS, CHARALAMPOS GEORGIOS; PERSECHINO, FLAVIA; PERSECHINO, SEVERINO
  • 11573/1560796 - 2021 - Vitiligo with Progressive Repigmentation during Secukinumab Treatment in a Patient with Psoriatic Arthritis. A Case Report (01i Case report)
    GIORDANO, DOMENICO; MAGRI, FRANCESCA; PERSECHINO, FLAVIA; CAPALBO, ALESSANDRO; PERSECHINO, SEVERINO
  • 11573/1553792 - 2021 - Expression profile of fibroblast growth factor receptors, keratinocyte differentiation markers, and epithelial mesenchymal transition-related genes in actinic keratosis. A possible predictive factor for malignant progression? (01a Articolo in rivista)
    PERSECHINO, FLAVIA; RANIERI, DANILO; GUTTIERI, LUISA; NANNI, MONICA; TORRISI, MARIA ROSARIA; BELLEUDI, FRANCESCA
  • 11573/1338251 - 2019 - Treatment of refractory conjunctivitis associated to dupilumab with topical pimecrolimus applied to the eyelid skin (01a Articolo in rivista)
    SERNICOLA, ALVISE; GATTAZZO, IRENE; DI STASO, FEDERICO; GIORDANO, DOMENICO; CAPALBO, ALESSANDRO; PERSECHINO, FLAVIA; SCUDERI, GIANLUCA; PERSECHINO, SEVERINO
  • 11573/1652316 - 2022 - An update on ophthalmological perspectives in oculodermal melanocytosis (Nevus of Ota) (01d Recensione)
    ABDOLRAHIMZADEH, SOLMAZ; PUGI, DAMIANO MARIA; MANNI, PRISCILLA; IODICE, CLEMENTE MARIA; PERSECHINO, FLAVIA; SCUDERI, GIANLUCA
  • 11573/1654762 - 1991 - Incidental prostate carcinoma: 4-year follow-up folowing treatment with cyproterone acetate,IL CARCINOMA PROSTATICO INCIDENTALE: QUATTRO ANNI DI FOLLOW-UP DOPO TERAPIA CON CIPROTERONE ACETATO (01a Articolo in rivista)
    DI SILVERIO, FRANCO; D'ERAMO, GIUSEPPE; CAPONERA, MAURO; PERSECHINO, FLAVIA; SCIARRA, ALESSANDRO
  • 11573/1482891 - 2018 - Improving the aging of the neck: combined treatments (04b Atto di convegno in volume)
    PERSECHINO, FLAVIA; PELLACANI, GIOVANNI
  • 11573/1482902 - 2018 - Skin above the knees: treatments for a difficult area (04b Atto di convegno in volume)
    PERSECHINO, FLAVIA; PELLACANI, GIOVANNI
  • 11573/1346208 - 2019 - Reed syndrome: A case report and dermatoscopic features (01i Case report)
    CHELLO, CAMILLA; MAGRI, FRANCESCA; GIORDANO, DOMENICO; PERSECHINO, FLAVIA; TAMMARO, ANTONELLA; PERSECHINO, SEVERINO
  • 11573/1657122 - 2022 - The FGFR2c/PKCε axis controls MCL-1-Mediated invasion in pancreatic ductal adenocarcinoma cells: perspectives for innovative target therapies (01a Articolo in rivista)
    RANIERI, DANILO; FRENCH, DEBORAH; PERSECHINO, FLAVIA; GUTTIERI, LUISA; TORRISI, MARIA ROSARIA; BELLEUDI, FRANCESCA
  • 11573/1656523 - 2022 - Biosimilar versus originator etanercept: a real-life clinical study (01l Trial clinico)
    GIORDANO, DOMENICO; CAPALBO, ALESSANDRO; GAGLIOSTRO, NAZARENO; BALAMPANOS, CHARALAMPOS GEORGIOS; PERSECHINO, FLAVIA; ULISSE, SALVATORE; PERSECHINO, SEVERINO; PELLACANI, GIOVANNI
  • 11573/987087 - 2017 - Plasticity of immune system vs. memory therapy IST (01a Articolo in rivista)
    TAMMARO, ANTONELLA; ROMANO, IRENE; PERSECHINO, FLAVIA; PERSECHINO, SEVERINO
  • 11573/637476 - 2014 - Decreased expression of KGF/FGF7 and its receptor in pathological hypopigmentation. (01a Articolo in rivista)
    PERSECHINO, FLAVIA; BELLEUDI, FRANCESCA; SCROFANI, CRISTINA; RAFFA, SALVATORE; PERSECHINO, SEVERINO; TORRISI, MARIA ROSARIA
  • 11573/488313 - 2012 - Magnesium stearate: an underestimated allergen (01a Articolo in rivista)
    TAMMARO, ANTONELLA; PERSECHINO, FLAVIA; PERSECHINO, SEVERINO
  • 11573/506781 - 2012 - xeroderma pigmentosum: the star’s sons. case report and review of the literature. (01a Articolo in rivista)
    MIRAGLIA, EMANUELE; CURATOLO, PIETRO; PERSECHINO, FLAVIA; CALVIERI, STEFANO; GIUSTINI, SANDRA
  • 11573/1191194 - 2018 - A new single red nodule on the abdomen of a woman with history of endometrial carcinoma: Noninvasive evaluation and histologic correlation (01i Case report)
    PERSECHINO, FLAVIA; FRANCESCHINI, CHIARA
  • 11573/1483171 - 2017 - Reflectance confocal microscopy features of regression in congenital naevus: case report (01a Articolo in rivista)
    PERSECHINO, FLAVIA; PELLACANI, GIOVANNI

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