Death-associated protein kinase loss of expression is a new marker for breast cancer prognosis.

Abstract

PURPOSE:

Death-associated protein (DAP)-kinase is a new Ser/Thr kinase involved in cell apoptosis and tumor suppression, the expression of which has been correlated to invasive potential and metastasis in several human neoplastic tissues. We analyzed the level of DAP-kinase expression in breast cancer specimens and its correlation with survival.

EXPERIMENTAL DESIGN:

One hundred twenty-eight breast cancer specimens were analyzed by immunohistochemistry. Patient records were studied retrospectively for demographic characteristics, clinical data, hormonal treatment, outcome, and survival. DAP-kinase protein expression was also studied in normal breast cells primary cultures under estrogen and antiestrogen treatment.

RESULTS:

Among the 128 patients, 30 showed a DAP-kinase staining < or = 20%, whereas 98 had a staining over 20%. Mean follow-up time was 62 months. The association between tumor Scarff-Bloom and Richardson grade (P = 0.009), estrogen receptor and progesterone receptor expression (P = 0.002 and 0.001, respectively), tumor size (P = 0.05), Bcl-2 expression (P = 0.004), and DAP-kinase immunostaining in the ductal carcinoma group was highly significant. Overall (64 months) and disease-free (63 months) survival in the high DAP-kinase expression group were significantly longer compared with the women whose tumors showed a loss of DAP-kinase expression (51 and 43 months, respectively). DAP-kinase protein was strongly expressed in normal breast tissue and in human breast epithelial cells primary cultures. Estradiol decreased DAP-kinase expression in these cells, arguing for hormonal regulation of the protein.

CONCLUSIONS:

Loss of DAP-kinase expression negatively correlates to survival and positively correlates to the probability of recurrence in a very significant manner. DAP-kinase thus constitutes a novel and independent prognosis marker for breast cancer.

• Authors: Delphine Lévy, Geneviève Plu-Bureau, Yves Decroix, Danielle Hugol, William Rostène, Adi Kimchi, Anne Gompel
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 10 Issue 9 Pg. 3124-30 (May 01 2004) ISSN: 1078-0432 [Print] United States
• PMID: 15131053 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• Apoptosis Regulatory Proteins
• Biomarkers, Tumor
• Estrogen Receptor Modulators
• Proto-Oncogene Proteins c-bcl-2
• Receptors, Estrogen
• Receptors, Progesterone
• Tamoxifen
• RU 58668
• Estradiol
• Death-Associated Protein Kinases
• Calcium-Calmodulin-Dependent Protein Kinases

Topics

• Antineoplastic Agents, Hormonal (therapeutic use)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins
• Biomarkers, Tumor (biosynthesis)
• Breast (cytology, drug effects, enzymology)
• Breast Neoplasms (drug therapy, enzymology, pathology)
• Calcium-Calmodulin-Dependent Protein Kinases (biosynthesis)
• Cell Division (drug effects)
• Cell Line, Tumor
• Cells, Cultured
• Death-Associated Protein Kinases
• Epithelial Cells (drug effects, enzymology)
• Estradiol (analogs & derivatives, pharmacology)
• Estrogen Receptor Modulators (pharmacology)
• Female
• Humans
• Immunohistochemistry
• Prognosis
• Proportional Hazards Models
• Proto-Oncogene Proteins c-bcl-2 (analysis)
• Receptors, Estrogen (analysis)
• Receptors, Progesterone (analysis)
• Survival Analysis
• Tamoxifen (therapeutic use)