title: The role of immunohistochemistry in discriminating primary from secondary extramammary Paget disease.
abstract: BACKGROUND
  Extramammary Paget disease (EMPD) is categorized into 2 groups: primary EMPD or EMPD secondary to underlying malignancy. Primary EMPD has a better prognosis, and the ability to distinguish between the 2 subsets has clinical relevance. Recent studies have suggested that immunostains, including cytokeratin (CK) 7, CK20, and BRST-2, distinguish between the 2 groups. We analyzed a large series of EMPD with an expanded immunohistochemical panel to assess its value in distinguishing primary from secondary disease.
  
  
  METHODS
  Formalin-fixed, paraffin-embedded sections of 98 EMPD specimens from 61 patients (45 primary and 16 secondary) were immunostained with CK7, CK20, HER-2/neu, BRST-2, CDX2, androgen receptor (AR), and cyclin D1. The study included 44 women and 17 men (median age: 73 years). Median follow-up time was 47 months.
  
  
  RESULTS
  All EMPD specimens were vibrantly positive for CK7. The frequency of positivity for all EMPD samples was CK20 (28%), BRST-2 (40%), HER-2/neu (64%), CDX2 (10%), AR (16%), and cyclin D1 (76%). For primary EMPD, the frequency of positivity was CK20 (22%), BRST-2 (48%), HER-2/neu (65%), CDX2 (2%), AR (21%), and cyclin D1 (84%). For secondary EMPD, the frequency of positivity was CK20 (50%), BRST-2 (25%), HER-2/neu (60%), CDX2 (33%), AR (0%), and cyclin D1 (53%). Notably, all 6 of 7 cases of EMPD secondary to an anorectal adenocarcinoma tested were HER-2/neu negative and 5 of those 6 cases (80%) were CDX2 positive.
  
  
  CONCLUSIONS
  The role of CK7, CK20, and BRST-2 in distinguishing primary and secondary EMPD is limited because CK20 and BRST-2 were positive in large subsets of both groups. An expanded immunohistochemical panel, including HER-2/neu and CDX2, may be useful in discriminating primary EMPD from EMPD secondary to anorectal adenocarcinoma but fails to distinguish primary EMPD from EMPD secondary to urothelial or prostatic malignancy. The consistent overexpression of HER-2/neu in primary EMPD suggests a role for trastuzumab therapy in patients with recurrent disease.
authors.affiliation: Dermatology PC, West Des Moines, IA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Perrotto
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Abbott
authors.forename: Roger I
authors.initials: RI
authors.lastname: Ceilley
authors.forename: Iftikhar
authors.initials: I
authors.lastname: Ahmed
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000556:secondary*; D000368:Aged; D000369:Aged, 80 and over; D000071616:CDX2 Transcription Factor; D002352:Carrier Proteins / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D053554:Keratin-20 / Q000378:metabolism; D053552:Keratin-7 / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D010145:Paget Disease, Extramammary / Q000175:diagnosis* / Q000378:metabolism / Q000556:secondary*; D011471:Prostatic Neoplasms / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012004:Rectal Neoplasms / Q000473:pathology; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000556:secondary*; D014571:Urologic Neoplasms / Q000473:pathology
chemical_list: D000071616:CDX2 Transcription Factor; D002352:Carrier Proteins; D006023:Glycoproteins; D018398:Homeodomain Proteins; D053554:Keratin-20; D053552:Keratin-7; D026901:Membrane Transport Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C491270:CDX2 protein, human; C488892:PIP protein, human