Abstract
BACKGROUND. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays an important role in tumor growth and metastasis by regulating energy metabolism and inducing angiogenesis to survive cellular hypoxia. Increased levels of HIF-1α, the O2-regulated subunit of HIF-1, were noted during breast carcinogenesis. In this study, the prognostic value of HIF-1α expression and its correlation with various clinicopathologic variables in patients with invasive breast carcinoma were investigated. METHODS. Expression levels of HIF-1α, HER-2/neu, estrogen receptor, and progesterone receptor were analyzed in 150 patients with early-stage breast carcinoma by immunohistochemistry. HER-2/neu gene amplification was investigated with automated fluorescent in situ hybridization. The mitotic activity index, histologic grade, and tumor type were assessed in hematoxylin and eosinstained specimens. Clinical data included disease-free survival, overall survival, lymph node status, and tumor size. The data were analyzed with two-sided univariate and multivariate tests, with P values <0.05 considered significant. RESULTS. High levels of HIF-1α had an association of borderline significance with decreased overall survival (P = 0.059) and disease-free survival (P = 0.110) that was ascribed completely to the subgroup of women with lymph node negative tumors (n = 81 patients; P = 0.008 and P = 0.004, respectively). HER-2/neu immunoreactivity (P <0.001) and gene amplification (P <0.001), vascular endothelial growth factor expression (P = 0.016), and Ki-67 expression (P <0.001) were correlated strongly with HIF-1α positivity, although none of those factors had an independent effect on survival. CONCLUSIONS. Increased levels of HIF-la were associated independently with shortened survival in patients with lymph node negative breast carcinoma. Therefore, the use of immunohistochemical assessment of HIF-1α as a new predictor of poor outcome may improve clinical decision-making regarding adjuvant treatment of patients with lymph node negative breast carcinoma.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1573-1581 |
| Number of pages | 9 |
| Journal | Cancer |
| Volume | 97 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 15 2003 |
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Keywords
- Breast carcinoma
- Estrogen receptor
- HER-2/neu
- Hypoxia-inducible factor 1α
- Mitotic activity index
- Progesterone receptor
- Prognosis
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Levels of hypoxia-inducible factor-1α independently predict prognosis in patients with lymph node negative breast carcinoma. / Bos, Reinhard; Van der Groep, Petra; Greijer, Astrid E.; Shvarts, Avi; Meijer, Sybren; Pinedo, Herbert M.; Semenza, Gregg L; Van Diest, Paul J.; Van der Wall, Elsken.
In: Cancer, Vol. 97, No. 6, 15.03.2003, p. 1573-1581.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Levels of hypoxia-inducible factor-1α independently predict prognosis in patients with lymph node negative breast carcinoma
AU - Bos, Reinhard
AU - Van der Groep, Petra
AU - Greijer, Astrid E.
AU - Shvarts, Avi
AU - Meijer, Sybren
AU - Pinedo, Herbert M.
AU - Semenza, Gregg L
AU - Van Diest, Paul J.
AU - Van der Wall, Elsken
PY - 2003/3/15
Y1 - 2003/3/15
N2 - BACKGROUND. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays an important role in tumor growth and metastasis by regulating energy metabolism and inducing angiogenesis to survive cellular hypoxia. Increased levels of HIF-1α, the O2-regulated subunit of HIF-1, were noted during breast carcinogenesis. In this study, the prognostic value of HIF-1α expression and its correlation with various clinicopathologic variables in patients with invasive breast carcinoma were investigated. METHODS. Expression levels of HIF-1α, HER-2/neu, estrogen receptor, and progesterone receptor were analyzed in 150 patients with early-stage breast carcinoma by immunohistochemistry. HER-2/neu gene amplification was investigated with automated fluorescent in situ hybridization. The mitotic activity index, histologic grade, and tumor type were assessed in hematoxylin and eosinstained specimens. Clinical data included disease-free survival, overall survival, lymph node status, and tumor size. The data were analyzed with two-sided univariate and multivariate tests, with P values <0.05 considered significant. RESULTS. High levels of HIF-1α had an association of borderline significance with decreased overall survival (P = 0.059) and disease-free survival (P = 0.110) that was ascribed completely to the subgroup of women with lymph node negative tumors (n = 81 patients; P = 0.008 and P = 0.004, respectively). HER-2/neu immunoreactivity (P <0.001) and gene amplification (P <0.001), vascular endothelial growth factor expression (P = 0.016), and Ki-67 expression (P <0.001) were correlated strongly with HIF-1α positivity, although none of those factors had an independent effect on survival. CONCLUSIONS. Increased levels of HIF-la were associated independently with shortened survival in patients with lymph node negative breast carcinoma. Therefore, the use of immunohistochemical assessment of HIF-1α as a new predictor of poor outcome may improve clinical decision-making regarding adjuvant treatment of patients with lymph node negative breast carcinoma.
AB - BACKGROUND. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays an important role in tumor growth and metastasis by regulating energy metabolism and inducing angiogenesis to survive cellular hypoxia. Increased levels of HIF-1α, the O2-regulated subunit of HIF-1, were noted during breast carcinogenesis. In this study, the prognostic value of HIF-1α expression and its correlation with various clinicopathologic variables in patients with invasive breast carcinoma were investigated. METHODS. Expression levels of HIF-1α, HER-2/neu, estrogen receptor, and progesterone receptor were analyzed in 150 patients with early-stage breast carcinoma by immunohistochemistry. HER-2/neu gene amplification was investigated with automated fluorescent in situ hybridization. The mitotic activity index, histologic grade, and tumor type were assessed in hematoxylin and eosinstained specimens. Clinical data included disease-free survival, overall survival, lymph node status, and tumor size. The data were analyzed with two-sided univariate and multivariate tests, with P values <0.05 considered significant. RESULTS. High levels of HIF-1α had an association of borderline significance with decreased overall survival (P = 0.059) and disease-free survival (P = 0.110) that was ascribed completely to the subgroup of women with lymph node negative tumors (n = 81 patients; P = 0.008 and P = 0.004, respectively). HER-2/neu immunoreactivity (P <0.001) and gene amplification (P <0.001), vascular endothelial growth factor expression (P = 0.016), and Ki-67 expression (P <0.001) were correlated strongly with HIF-1α positivity, although none of those factors had an independent effect on survival. CONCLUSIONS. Increased levels of HIF-la were associated independently with shortened survival in patients with lymph node negative breast carcinoma. Therefore, the use of immunohistochemical assessment of HIF-1α as a new predictor of poor outcome may improve clinical decision-making regarding adjuvant treatment of patients with lymph node negative breast carcinoma.
KW - Breast carcinoma
KW - Estrogen receptor
KW - HER-2/neu
KW - Hypoxia-inducible factor 1α
KW - Mitotic activity index
KW - Progesterone receptor
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=0037443587&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037443587&partnerID=8YFLogxK
U2 - 10.1002/cncr.11246
DO - 10.1002/cncr.11246
M3 - Article
C2 - 12627523
AN - SCOPUS:0037443587
VL - 97
SP - 1573
EP - 1581
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 6
ER -