title: Immunohistochemical expression of ARID1A in penile squamous cell carcinomas: a tissue microarray study of 112 cases.
abstract: ARID1A, a member of the chromatin remodeling genes family, has been suggested as a novel tumor suppressor gene in gynecologic malignancies. However, its role in penile cancer has yet to be determined. This study assesses the immunohistochemical expression of ARID1A in penile squamous cell carcinoma (SCC) and its association with pathologic features, human papillomavirus (HPV) status, and previously reported mammalian target of rapamycin pathway markers in the same cohort. Four tissue microarrays were constructed from 112 cases of formalin-fixed, paraffin-embedded penile SCC from Paraguay. Each tumor was sampled 3 to 12 times. ARID1A expression was evaluated by immunohistochemistry using a polyclonal rabbit anti-ARID1A (BAF250A) antibody. An H score was calculated in each spot as the sum of expression intensity (0-3+) by extent (0%-100%). Median H score per case was used for statistical analysis. ARID1A expression was observed in all cases, ranging from 3% to 100% of tumor cells (median, 95%). In 96 cases (86%), ARID1A expression was observed in 90% or more tumor cells. HPV DNA was detected in 20 (38%) of 52 analyzed samples. There was a significant trend of association between ARID1A and histologic grade. ARID1A expression was not associated with histologic subtype (P = .61) or HPV status (P = .18). ARID1A expression decreased with decreasing levels of PTEN expression (P = .01). ARID1A was expressed in penile SCC, in most cases at high levels. A significant trend of association was found between histologic grade and ARID1A expression, with lower ARID1A expression, lower histologic grades, and decreased PTEN expression.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 31231.
authors.forename: Sheila F
authors.initials: SF
authors.lastname: Faraj
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 31231; Department of Scientific Research, Norte University, Asunción, 1614, Paraguay. Electronic address: alcideschaux@uninorte.edu.py.
authors.forename: Alcides
authors.initials: A
authors.lastname: Chaux
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 31231.
authors.forename: Nilda
authors.initials: N
authors.lastname: Gonzalez-Roibon
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 31231.
authors.forename: Enrico
authors.initials: E
authors.lastname: Munari
authors.affiliation: Instituto de Patología e Investigación, Asunción 1817, Paraguay.
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Cubilla
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 31231.
authors.forename: Ie-Ming
authors.initials: IeM
authors.lastname: Shih
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 31231; Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD 31231; Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 31231.
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D004268:DNA-Binding Proteins; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010412:Penile Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D046888:Tissue Array Analysis / Q000379:methods; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C112476:ARID1A protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors
keywords: ARID1A; BAF250A; Penile SCC; SWI/SNF; mTOR pathway