title: Concordant overexpression of p-FAK and p-ERK1/2 in extramammary Paget's disease.
abstract: Focal adhesion kinase (FAK) is a tyrosine kinase which is at the crossroad of extracellular signal-regulated kinase-1/2 (ERK1/2), PI3K/Akt, MAPK and JAK/STAT signaling pathways. We have previously reported that p-ERK1/2, p-Akt, p38MAPK and p-STAT3 are overexpressed in extramammary Paget's diseases (EMPD), this study aimed to examine the expression of phosphorylated (p)-FAK and p-ERK1/2 proteins in EMPD and to evaluate the relationships among them. Paraffin-embedded EMPD specimens (35 tissue samples from 33 patients with primary EMPD, including two samples of metastatic lymph nodes from two of the 33 patients) were subjected to immunohistochemical staining for p-FAK and p-ERK1/2. All of the 35 EMPD specimens, including all of six invasive EMPD and two metastatic lymph node specimens, showed cytoplasmic overexpression of p-FAK and nuclear overexpression of p-ERK1/2. The expression levels (% positive cells) of p-FAK and p-ERK1/2 (88.34 +/- 14.66 and 91.26 +/- 11.21%) in EMPD were significantly higher than those in normal skin (22.38 +/- 2.13 and 29.00 +/- 4.44%), respectively. The expression levels of p-FAK (95.38 +/- 4.57%) and p-ERK1/2 (96.25 +/- 5.01%) in the advanced EMPD showed slightly higher than that in the non-invasive EMPD (86.26 +/- 15.99 and 89.78 +/- 12.15%), respectively. There exhibited a significantly high positive correlation between expression levels of p-ERK1/2 and p-FAK in EMPD. The present study shows that the concordant overexpression of p-FAK and p-ERK1/2 in EMPD which is associated with the grade of malignancy of EMPD, indicating that p-FAK and p-ERK1/2 may play pivotal roles in the tumorigenesis and further malignant transduction of EMPD.
authors.affiliation: Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashiku, Fukuoka, 812-8582, Japan.
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Chen
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Moroi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Urabe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Makiko
authors.initials: M
authors.lastname: Kido
authors.forename: Sayaka
authors.initials: S
authors.lastname: Hayashida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uenotsuchi
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Tu
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010145:Paget Disease, Extramammary / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000502:physiology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3