Human AP endonuclease 1 (HAP1) protein expression in breast cancer correlates with lymph node status and angiogenesis

被引:59
作者
Kakolyris, S
Kaklamanis, L
Engels, K
Fox, SB
Taylor, M
Hickson, ID
Gatter, KC
Harris, AL [1 ]
机构
[1] Univ Oxford, John Radcliffe Hosp, Imperial Canc Res Fund, Mol Oncol Lab, Oxford OX3 9DU, England
[2] Univ Oxford, John Radcliffe Hosp, Dept Cellular Sci, Oxford OX3 9DU, England
[3] Univ Gen Hosp Iraklion, Dept Clin Oncol, GR-71110 Crete, Greece
[4] Churchill Hosp, Imperial Canc Res Fund, Clin Oncol Unit, Oxford OX3 7LJ, England
关键词
HAP1; breast cancer; immunohistochemistry; DNA repair;
D O I
10.1038/bjc.1998.194
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1169 / 1173
页数:5
相关论文
共 36 条
  • [11] GUEDSON JL, 1979, J HISTOCHEM CYTOCHEM, V27, P1131
  • [12] ANGIOGENESIS, ASSESSED BY PLATELET ENDOTHELIAL-CELL ADHESION MOLECULE ANTIBODIES, AS INDICATOR OF NODE METASTASES AND SURVIVAL IN BREAST-CANCER
    HORAK, ER
    LEEK, R
    KLENK, N
    LEJEUNE, S
    SMITH, K
    STUART, N
    GREENALL, M
    STEPNIEWSKA, K
    HARRIS, AL
    [J]. LANCET, 1992, 340 (8828) : 1120 - 1124
  • [13] CHEMICAL-CHANGES INDUCED IN DNA BY IONIZING-RADIATION
    HUTCHINSON, F
    [J]. PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, 1985, 32 : 115 - 154
  • [14] INTRACELLULAR-LOCALIZATION AND FUNCTION OF DNA-REPAIR METHYLTRANSFERASE IN HUMAN-CELLS
    ISHIBASHI, T
    NAKABEPPU, Y
    KAWATE, H
    SAKUMI, K
    HAYAKAWA, H
    SEKIGUCHI, M
    [J]. MUTATION RESEARCH-DNA REPAIR, 1994, 315 (03): : 199 - 212
  • [15] Kakolyris S, 1997, CANCER RES, V57, P1794
  • [16] NONPARAMETRIC-ESTIMATION FROM INCOMPLETE OBSERVATIONS
    KAPLAN, EL
    MEIER, P
    [J]. JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1958, 53 (282) : 457 - 481
  • [17] MUTATIONS OF A MUTS HOMOLOG IN HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER
    LEACH, FS
    NICOLAIDES, NC
    PAPADOPOULOS, N
    LIU, B
    JEN, J
    PARSONS, R
    PELTOMAKI, P
    SISTONEN, P
    AALTONEN, LA
    NYSTROMLAHTI, M
    GUAN, XY
    ZHANG, J
    MELTZER, PS
    YU, JW
    KAO, FT
    CHEN, DJ
    CEROSALETTI, KM
    FOURNIER, REK
    TODD, S
    LEWIS, T
    LEACH, RJ
    NAYLOR, SL
    WEISSENBACH, J
    MECKLIN, JP
    JARVINEN, H
    PETERSEN, GM
    HAMILTON, SR
    GREEN, J
    JASS, J
    WATSON, P
    LYNCH, HT
    TRENT, JM
    DELACHAPELLE, A
    KINZLER, KW
    VOGELSTEIN, B
    [J]. CELL, 1993, 75 (06) : 1215 - 1225
  • [18] EXPRESSION OF O(6)-ALKYLGUANINE-DNA-ALKYLTRANSFERASE INSITU IN OVARIAN AND HODGKINS TUMORS
    LEE, SM
    HARRIS, M
    RENNISON, J
    MCGOWN, A
    BROMLEY, M
    ELDER, RH
    RAFFERTY, JA
    CROWTHER, D
    MARGISON, GP
    [J]. EUROPEAN JOURNAL OF CANCER, 1993, 29A (09) : 1306 - 1312
  • [19] MUTAGENESIS BY APURINIC APYRIMIDINIC SITES
    LOEB, LA
    PRESTON, BD
    [J]. ANNUAL REVIEW OF GENETICS, 1986, 20 : 201 - 230
  • [20] MALINS DC, 1993, CANCER-AM CANCER SOC, V71, P3036, DOI 10.1002/1097-0142(19930515)71:10<3036::AID-CNCR2820711025>3.0.CO