title: Human AP endonuclease 1 (HAP1) protein expression in breast cancer correlates with lymph node status and angiogenesis.
abstract: Human AP endonuclease (HAP1) plays a major role in the repair of apurinic/apyrimidinic (AP) sites in cellular DNA. We used immunohistochemistry to examine the expression of HAP1 in normal breast and in 102 primary breast carcinomas. In normal breast epithelium, HAP1 had a uniformly nuclear localization. However, in lactating glandular epithelium, the expression of HAP1 was predominantly cytoplasmic. In carcinomas, both nuclear and cytoplasmic (44%), cytoplasmic (28%) or nuclear staining (24%) were observed. In four cases (4%), no HAP1 expression was detected. All patterns of expression for HAP1 were demonstrated for ductal carcinomas in situ (DCIS), although comedo-type DCIS were usually accompanied by mostly cytoplasmic staining. Similarly, the HAP1 expression in regions of invasive tumour necrosis was cytoplasmic. Pure nuclear HAP1 expression was significantly correlated with low angiogenesis (P = 0.007) and negative lymph node status (P = 0.001). In contrast, cases with cytoplasmic as well as nuclear staining were associated with poor prognostic factors, such as high angiogenesis (P = 0.03) and node positivity (P = 0.03). The pure nuclear staining may be related to better differentiation, as in normal breast, and hence better prognostic features, and cytoplasmic staining to a more metabolically active phenotype with high protein synthesis, as in lactating breast.
authors.affiliation: Department of Cellular Science, John Radcliffe Hospital, University of Oxford, UK.
authors.forename: S
authors.initials: S
authors.lastname: Kakolyris
authors.forename: L
authors.initials: L
authors.lastname: Kaklamanis
authors.forename: K
authors.initials: K
authors.lastname: Engels
authors.forename: S B
authors.initials: SB
authors.lastname: Fox
authors.forename: M
authors.initials: M
authors.lastname: Taylor
authors.forename: I D
authors.initials: ID
authors.lastname: Hickson
authors.forename: K C
authors.initials: KC
authors.lastname: Gatter
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase