title: Expression of the p40 isoform of p63 has high specificity for cutaneous sarcomatoid squamous cell carcinoma.
abstract: Cutaneous spindle cell malignancies such as sarcomatoid squamous cell carcinoma (SCC), leiomyosarcoma, desmoplastic melanoma (DM) and atypical fibroxanthoma (AFX) may be morphologically indistinguishable, yet accurate diagnosis is important for appropriate clinical management. The distinction among these entities relies on immunohistochemical evaluation for epidermal, muscle or melanocytic differentiation. Epidermal differentiation markers include cytokeratins and p63. p63 is expressed as two distinct isoforms, ΔNp63 (p40) and TAp63. p40 positivity is highly specific for pulmonary SCC and head and neck sarcomatoid SCC. We examined the utility of p40 vs. p63 immunostaining in the differentiation of a variety of cutaneous spindle cell malignancies, including sarcomatoid SCC (n = 27), AFX (n = 34) and DM (n = 10). p40 was less sensitive than p63 for detecting sarcomatoid SCC (56% and 81%, respectively). p63 and p40 were comparably specific for sarcomatoid SCC relative to AFX, with only rare weak staining of tumor cells for p63 and/or p40 in a minority of AFX cases, including one case with approximately 10% of cells staining weakly for p40. All cases of DM were negative for p40 and p63. Our results support continued use of p63 for diagnosis of cutaneous sarcomatoid SCC because of greater sensitivity relative to p40.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
authors.forename: Thanh T
authors.initials: TT
authors.lastname: Ha Lan
authors.forename: Stephanie J T
authors.initials: SJ
authors.lastname: Chen
authors.forename: David P
authors.initials: DP
authors.lastname: Arps
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Fullen
authors.forename: Rajiv M
authors.initials: RM
authors.lastname: Patel
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqui
authors.forename: Shannon
authors.initials: S
authors.lastname: Carskadon
authors.forename: Nallasivam
authors.initials: N
authors.lastname: Palanisamy
authors.forename: Paul W
authors.initials: PW
authors.lastname: Harms
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000032:analysis* / Q000096:biosynthesis; D008875:Middle Aged; D020033:Protein Isoforms; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000175:diagnosis*; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000032:analysis* / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins / Q000032:analysis* / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; C081876:CKAP4 protein, human; D008565:Membrane Proteins; D020033:Protein Isoforms; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
keywords: atypical fibroxanthoma; deltaNp63; p40; p63; squamous cell carcinoma