Elevated CAIX expression is associated with an increased risk of distant failure in early-stage cervical cancer

John P. Kirkpatrick, Zahid N. Rabbani, Rex C. Bentley, Matt E. Hardee, Seth Karol, Jeffrey Meyer, Egbert Oosterwijk, Laura Havrilesky, Angeles Alvarez Secord, Zeljko Vujaskovic, Mark W. Dewhirst, Ellen L. Jones

Research output: Contribution to journalArticle

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Abstract

Tumor hypoxia is associated with adverse outcome in many malignancist. The goal of this study was to determine if elevated expression of carbonic, anhydrase EX (CAIX), a biomarker of hypoxia, predicts fot recurrence in early-stage cervical cancer, The charts of all patients with early-stage, cervical cancer, primarily FIGO IB, treated by radical hysterectomy at our institution from 1988-2001 were reviewed, Adequate pathologic specimens from patients who recurred or who had at least three years follow-up and remianed, disease-free were stained for CAIX. An immunohistochemical score (IHC) was generated from the extent/ intensity of staining. Outcome, as-measured. by freedom from recurrence (FFR); distant metastases (FFDM) and local recurrence (FFLR), was analyzed as a function of age, IHC, lymph node status (LN) and histology. Forty-two relapsing patients and 76 non-relapsing patients were evaluated. In univariate analysis, +LN, though not IHC or histology, was a significant predictor of any recurrence. Both +LN and higher IHC, were associated with decreased FFDM but not FFLR. Patients with both +LN and elevated IHC more frequently exhibited distant metastises as first site of failure. (5-yedr FFDM 50%) than patients with only. +LN, elevated IHC or neither feature (70, 85 and 95%, respectively, p = 0.0004). In multivariable analysis, only +LN was significantly associated with poorer FFDM (hazard ratio 4.6, p=0.0015) though there was a strong trend with elevated CAIX expression (p = 0.069). Elevated CAIX expressions is associated with more frequent distant metastases in early-stage cervical cancer, suggesting that patients with this characteristic may benefit from more aggressive treatment.

Original languageEnglish (US)
Pages (from-to)45-55
Number of pages11
JournalBiomarker Insights
Volume2008
Issue number3
StatePublished - 2008

Fingerprint

Histology
Uterine Cervical Neoplasms
Lymph Nodes
Carbonic Anhydrases
Biomarkers
Recurrence
Tumors
Hazards
Neoplasm Metastasis
Hysterectomy
Staining and Labeling

Keywords

  • Carbonic anhydrase IX
  • Tumour hypoxia
  • Uterine cervical cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Biochemistry, medical

Cite this

Kirkpatrick, J. P., Rabbani, Z. N., Bentley, R. C., Hardee, M. E., Karol, S., Meyer, J., ... Jones, E. L. (2008). Elevated CAIX expression is associated with an increased risk of distant failure in early-stage cervical cancer. Biomarker Insights, 2008(3), 45-55.

Elevated CAIX expression is associated with an increased risk of distant failure in early-stage cervical cancer. / Kirkpatrick, John P.; Rabbani, Zahid N.; Bentley, Rex C.; Hardee, Matt E.; Karol, Seth; Meyer, Jeffrey; Oosterwijk, Egbert; Havrilesky, Laura; Secord, Angeles Alvarez; Vujaskovic, Zeljko; Dewhirst, Mark W.; Jones, Ellen L.

In: Biomarker Insights, Vol. 2008, No. 3, 2008, p. 45-55.

Research output: Contribution to journalArticle

Kirkpatrick, JP, Rabbani, ZN, Bentley, RC, Hardee, ME, Karol, S, Meyer, J, Oosterwijk, E, Havrilesky, L, Secord, AA, Vujaskovic, Z, Dewhirst, MW & Jones, EL 2008, 'Elevated CAIX expression is associated with an increased risk of distant failure in early-stage cervical cancer', Biomarker Insights, vol. 2008, no. 3, pp. 45-55.
Kirkpatrick JP, Rabbani ZN, Bentley RC, Hardee ME, Karol S, Meyer J et al. Elevated CAIX expression is associated with an increased risk of distant failure in early-stage cervical cancer. Biomarker Insights. 2008;2008(3):45-55.
Kirkpatrick, John P. ; Rabbani, Zahid N. ; Bentley, Rex C. ; Hardee, Matt E. ; Karol, Seth ; Meyer, Jeffrey ; Oosterwijk, Egbert ; Havrilesky, Laura ; Secord, Angeles Alvarez ; Vujaskovic, Zeljko ; Dewhirst, Mark W. ; Jones, Ellen L. / Elevated CAIX expression is associated with an increased risk of distant failure in early-stage cervical cancer. In: Biomarker Insights. 2008 ; Vol. 2008, No. 3. pp. 45-55.
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abstract = "Tumor hypoxia is associated with adverse outcome in many malignancist. The goal of this study was to determine if elevated expression of carbonic, anhydrase EX (CAIX), a biomarker of hypoxia, predicts fot recurrence in early-stage cervical cancer, The charts of all patients with early-stage, cervical cancer, primarily FIGO IB, treated by radical hysterectomy at our institution from 1988-2001 were reviewed, Adequate pathologic specimens from patients who recurred or who had at least three years follow-up and remianed, disease-free were stained for CAIX. An immunohistochemical score (IHC) was generated from the extent/ intensity of staining. Outcome, as-measured. by freedom from recurrence (FFR); distant metastases (FFDM) and local recurrence (FFLR), was analyzed as a function of age, IHC, lymph node status (LN) and histology. Forty-two relapsing patients and 76 non-relapsing patients were evaluated. In univariate analysis, +LN, though not IHC or histology, was a significant predictor of any recurrence. Both +LN and higher IHC, were associated with decreased FFDM but not FFLR. Patients with both +LN and elevated IHC more frequently exhibited distant metastises as first site of failure. (5-yedr FFDM 50{\%}) than patients with only. +LN, elevated IHC or neither feature (70, 85 and 95{\%}, respectively, p = 0.0004). In multivariable analysis, only +LN was significantly associated with poorer FFDM (hazard ratio 4.6, p=0.0015) though there was a strong trend with elevated CAIX expression (p = 0.069). Elevated CAIX expressions is associated with more frequent distant metastases in early-stage cervical cancer, suggesting that patients with this characteristic may benefit from more aggressive treatment.",
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AU - Rabbani, Zahid N.

AU - Bentley, Rex C.

AU - Hardee, Matt E.

AU - Karol, Seth

AU - Meyer, Jeffrey

AU - Oosterwijk, Egbert

AU - Havrilesky, Laura

AU - Secord, Angeles Alvarez

AU - Vujaskovic, Zeljko

AU - Dewhirst, Mark W.

AU - Jones, Ellen L.

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N2 - Tumor hypoxia is associated with adverse outcome in many malignancist. The goal of this study was to determine if elevated expression of carbonic, anhydrase EX (CAIX), a biomarker of hypoxia, predicts fot recurrence in early-stage cervical cancer, The charts of all patients with early-stage, cervical cancer, primarily FIGO IB, treated by radical hysterectomy at our institution from 1988-2001 were reviewed, Adequate pathologic specimens from patients who recurred or who had at least three years follow-up and remianed, disease-free were stained for CAIX. An immunohistochemical score (IHC) was generated from the extent/ intensity of staining. Outcome, as-measured. by freedom from recurrence (FFR); distant metastases (FFDM) and local recurrence (FFLR), was analyzed as a function of age, IHC, lymph node status (LN) and histology. Forty-two relapsing patients and 76 non-relapsing patients were evaluated. In univariate analysis, +LN, though not IHC or histology, was a significant predictor of any recurrence. Both +LN and higher IHC, were associated with decreased FFDM but not FFLR. Patients with both +LN and elevated IHC more frequently exhibited distant metastises as first site of failure. (5-yedr FFDM 50%) than patients with only. +LN, elevated IHC or neither feature (70, 85 and 95%, respectively, p = 0.0004). In multivariable analysis, only +LN was significantly associated with poorer FFDM (hazard ratio 4.6, p=0.0015) though there was a strong trend with elevated CAIX expression (p = 0.069). Elevated CAIX expressions is associated with more frequent distant metastases in early-stage cervical cancer, suggesting that patients with this characteristic may benefit from more aggressive treatment.

AB - Tumor hypoxia is associated with adverse outcome in many malignancist. The goal of this study was to determine if elevated expression of carbonic, anhydrase EX (CAIX), a biomarker of hypoxia, predicts fot recurrence in early-stage cervical cancer, The charts of all patients with early-stage, cervical cancer, primarily FIGO IB, treated by radical hysterectomy at our institution from 1988-2001 were reviewed, Adequate pathologic specimens from patients who recurred or who had at least three years follow-up and remianed, disease-free were stained for CAIX. An immunohistochemical score (IHC) was generated from the extent/ intensity of staining. Outcome, as-measured. by freedom from recurrence (FFR); distant metastases (FFDM) and local recurrence (FFLR), was analyzed as a function of age, IHC, lymph node status (LN) and histology. Forty-two relapsing patients and 76 non-relapsing patients were evaluated. In univariate analysis, +LN, though not IHC or histology, was a significant predictor of any recurrence. Both +LN and higher IHC, were associated with decreased FFDM but not FFLR. Patients with both +LN and elevated IHC more frequently exhibited distant metastises as first site of failure. (5-yedr FFDM 50%) than patients with only. +LN, elevated IHC or neither feature (70, 85 and 95%, respectively, p = 0.0004). In multivariable analysis, only +LN was significantly associated with poorer FFDM (hazard ratio 4.6, p=0.0015) though there was a strong trend with elevated CAIX expression (p = 0.069). Elevated CAIX expressions is associated with more frequent distant metastases in early-stage cervical cancer, suggesting that patients with this characteristic may benefit from more aggressive treatment.

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