Expression of checkpoint kinase 2 in breast carcinomas: correlation with key regulators of tumor cell proliferation, angiogenesis, and survival.
Checkpoint kinase 2 (Chk2) is a cell-cycle-checkpoint kinase that may act as a tumor suppressor gene due to its important role in DNA damage signaling and cell cycle regulation. The role of Chk2 expression in mammary tumorigenesis, however, is still poorly understood. This study was designed to assess the relationship between the expression of Chk2 and well-established prognostic factors, including disease-free-survival and overall survival; and several regulators of cell proliferation and invasiveness in breast carcinomas, including oncogenes, tumor suppressor genes, apoptosis-related proteins, and angiogenesis-related markers. Immunohistochemistry with 27 primary antibodies was performed in 100 formalin-fixed paraffin-embedded samples of not otherwise specified invasive ductal carcinomas. Clinical data were retrieved from medical files. In normal mammary parenchyma adjacent to the tumors Chk2 stained the nuclei of epithelial cells. Downexpression of Chk2 protein was observed in 23 carcinomas and correlated with advanced disease. Among the regulators of tumor cell proliferation and invasiveness analyzed, the downexpression of Chk2 correlated only with reduced expression of p27 and telomerase. There was no difference between the overall survival and disease-free survival rates according to Chk2 status. In conclusion, Chk2 correlated with reduced expression of h-TERT and p27, but not with angiogenic factors. Chk2 expression also did not interfere in the outcome of the patients.
Ribeiro-Silva
A
A
Department of Pathology, Faculty of Medicine of Ribeirão Preto, SP, Brazil. arsilva@fmrp.usp.br
Moutinho
M A Koyota
MA
Moura
H Becker de
HB
Vale
F Ribeiro do
FR
Zucoloto
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000473:pathology*; D016923:Cell Death / Q000235:genetics; D049109:Cell Proliferation; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000032:analysis* / Q000502:physiology; D015996:Survival Rate; D019098:Telomerase / Q000032:analysis / Q000235:genetics / Q000502:physiology
D004268:DNA-Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; C413374:p27 antigen; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases; C509186:TERT protein, human; D019098:Telomerase