title: The utility of PAX8 and IMP3 immunohistochemical stains in the differential diagnosis of benign, premalignant, and malignant endocervical glandular lesions.
abstract: Glandular lesions of the endocervix can be diagnostically challenging and occasionally the differential diagnosis includes endocervical adenocarcinoma in situ (EC AIS) and well-differentiated endocervical adenocarcinoma (ECA). PAX8 and IMP3 are two markers which have not been well studied in the endocervix. Our aim was to evaluate their immunohistochemical (IHC) expression in benign and malignant endocervical glandular lesions as well as to compare them to the traditionally used panel (Ki-67, p16, CEA).
  
  
  METHODS
  We searched our surgical pathology files for a cohort of benign endocervical glandular lesions as well as premalignant and malignant groups including EC AIS and ECA. An IHC panel consisting of PAX8, IMP3, Ki-67, p16, and CEA was performed on all cases. Immunoreactivity was scored on a degree of positivity (S0=no immunoreactivity, S1=up to 10% cells, S2=between 10 and 50% cells, S3=>50% cells) and intensity (Int0 - absent, Int1 - mild/faint, Int2 - moderate, Int3 - strong).
  
  
  RESULTS
  PAX8 showed diffuse positivity (S3) with at least a moderate intensity of staining (Int2) in the benign group. PAX8 was focal (S1) in ECA and faint (Int1), compared to EC AIS, which was moderate (S2) and faint (Int1). IMP3 expression was focal in the benign group (S1), moderate (S2) in EC AIS and moderate-to-diffuse (S2-3) in ECA. IMP3 intensity was faint (Int1) in benign lesions, moderate (Int2) in EC AIS, and strong (Int3) in ECA. Significant Ki-67, p16, and CEA expression was noted in the premalignant/malignant cohort.
  
  
  CONCLUSIONS
  PAX8 and IMP3 can be helpful in the differential diagnosis of benign vs. malignant endocervical glandular lesions. Our study, however, shows that there is some degree of overlap of staining in both the benign and malignant group. As such, PAX8 and IMP3 should always be interpreted with caution and in combination with the histomorphology.
authors.affiliation: Hartford Hospital, Department of Pathology and Laboratory Medicine, Hartford, CT 06102, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Danialan
authors.forename: Margaret
authors.initials: M
authors.lastname: Assaad
authors.forename: Jason
authors.initials: J
authors.lastname: Burghardt
authors.forename: Pamela
authors.initials: P
authors.lastname: Newcomb
authors.forename: Richard W
authors.initials: RW
authors.lastname: Cartun
authors.forename: Srinivas
authors.initials: S
authors.lastname: Mandavilli
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000175:diagnosis; D002272:Carcinoembryonic Antigen / Q000032:analysis; D002278:Carcinoma in Situ / Q000737:chemistry / Q000175:diagnosis; D019941:Cyclin-Dependent Kinase Inhibitor p16; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000032:analysis*; D011230:Precancerous Conditions / Q000737:chemistry / Q000175:diagnosis*; D016601:RNA-Binding Proteins / Q000032:analysis*; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000175:diagnosis*
chemical_list: C000614131:CDKN2A protein, human; D002272:Carcinoembryonic Antigen; D019941:Cyclin-Dependent Kinase Inhibitor p16; C498780:IGF2BP3 protein, human; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D016601:RNA-Binding Proteins
keywords: Cervical adenocarcinoma; Cervical adenocarcinoma in situ; IMP3; Immunohistochemistry; Ki-67; PAX8