title: Endocervical glandular neoplasia associated with lobular endocervical glandular hyperplasia is HPV-independent and correlates with carbonic anhydrase-IX expression: a Gynaecological Oncology Group Study.
abstract: BACKGROUND
  Lobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. It has been proposed that LEGH may represent a precursor lesion to a group of mucinous adenocarcinoma with gastric phenotype (GA) that is independent of high-risk human papillomavirus (H-HPV) infection. Carbonic anhydrase-IX (CA-IX) is highly expressed in conventional glandular lesions (CGLs). However, expression of CA-IX in LEGH or GA has not been studied.
  
  
  METHODS
  In all, 12 CGLs, 7 LEGHs, 6 LEGHs with coexisting adenocarcinoma in situ (AIS, 3) and GA (3) were identified from Japanese women with a cytological diagnosis of atypical glandular cells of undetermined significance. Immunostaining was used to detect CA-IX and p16(INK)4(a) (hereafter termed p16) protein expression in the tissues and CA-IX protein expression in the Papanicolaou smears (PSs). Polymerase chain reaction was used to detect H-HPV DNA in liquid-based cytology.
  
  
  RESULTS
  Out of 12 (83%) CGLs, 10 were positive with H-HPV and high levels of CA-IX expression were seen in all (100%) cases. P16 protein expression was observed in 11 out of 12 (92%) cases. None of the LEGHs, LEGHs with AIS or GA were positive for H-HPV and only 8 out of 13 (62%) showed focal weak (1+) p16 expression. In contrast, all cases (100%) exhibited strong CA-IX protein expression.
  
  
  CONCLUSIONS
  Our study suggests that there are different molecular mechanisms of carcinogenesis resulting in CGLs vs LEGHs associated with AIS or GA. There is also a possible link between LEGHs and GAs. Furthermore, CA-IX expression may serve as a useful biomarker for the detection of GAs in the absence of H-HPV infection.
authors.affiliation: Department of Epidemiology, University of California, Irvine, School of Medicine, Irvine, CA, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Liao
authors.forename: W H
authors.initials: WH
authors.lastname: Rodgers
authors.forename: J
authors.initials: J
authors.lastname: Kauderer
authors.forename: K M
authors.initials: KM
authors.lastname: Darcy
authors.forename: R
authors.initials: R
authors.lastname: Carter
authors.forename: N
authors.initials: N
authors.lastname: Susumu
authors.forename: S
authors.initials: S
authors.lastname: Nagao
authors.forename: J L
authors.initials: JL
authors.lastname: Walker
authors.forename: M
authors.initials: M
authors.lastname: Hatae
authors.forename: E J
authors.initials: EJ
authors.lastname: Stanbridge
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000201:enzymology / Q000473:pathology / Q000821:virology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism*; D018275:Carcinoma, Lobular / Q000201:enzymology / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000201:enzymology / Q000473:pathology* / Q000821:virology; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology / Q000473:pathology* / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000201:enzymology / Q000473:pathology* / Q000821:virology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D013274:Stomach Neoplasms / Q000201:enzymology / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000473:pathology* / Q000821:virology
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004279:DNA, Viral; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases