Invasive oxygen measurements and pimonidazole labeling in human cervix carcinoma

Nordsmark, Marianne; Loncaster, Juliette A; Chou, Shu-Chuan; Havsteen, Hanne; Lindegaard, J.C.; Davidson, Susan E; Varia, Mahesh A.; West, Catharine M L; Hunter, Robin D; Overgaard, Jens; Raleigh, James A.

doi:10.1016/s0360-3016(00)01493-0

Cited by 77 publications

(52 citation statements)

References 20 publications

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“…The availability of histological markers of hypoxia has widened the opportunity to study tumours in more remote sites. The binding of pimonidazole adducts is perhaps the most robust and widely accepted marker of cellular hypoxia (Varia et al, 1998;Nordsmark et al, 2001;Raleigh et al, 2001;Kaanders et al, 2002). However, the technique is invasive as it requires an injection of pimonidazole to be scheduled prior to surgical procedures.…”

Section: Discussionmentioning

confidence: 99%

GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON

et al. 2003

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Glucose transporter-1 protein (GLUT1) and carbonic anhydrase IX (CAIX) are regulated by hypoxia inducible factor-1 (HIF-1) and have been studied as putative intrinsic cellular markers for hypoxia. This study directly compares CAIX and GLUT1 with pimonidazole binding in a prospective series of bladder cancer patients and also studies the prognostic significance of the markers, in combination with vascularity and proliferation, in a retrospective series of bladder cancer patients treated in a phase II trial of radical radiotherapy with carbogen and nicotinamide (ARCON). A total of 21 patients with a diagnosis of transitional cell carcinoma of the bladder received 0.5 g m À2 pimonidazole. Serial tumour sections were stained for pimonidazole, GLUT1 and CAIX and compared. Tissue sections obtained from a series of 64 patients previously treated for invasive bladder cancer using ARCON were stained for GLUT1 and CAIX together with Ki-67 and CD31/34. There was a good geographical colocalisation of both intrinsic markers with pimonidazole and a highly significant agreement in individual patients; correlation coefficients were 0.82 (P ¼ 0.0001) for GLUT1 and 0.74 (Po0.0001) for CAIX. In both series of patients, the intrinsic hypoxia markers were highly correlated with each other and a correlation with proliferation was also evident in the retrospective study. In univariate and multivariate analyses, GLUT1 and CAIX were independent predictors for overall and cause specific survival. The hypoxia markers did not predict for local control or metastases-free survival although higher Ki-67 indices showed a trend towards local failure. The data suggest that both hypoxia modification and accelerated treatment may be valid treatment options in bladder cancer.

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Section: Discussionmentioning

confidence: 99%

GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON

et al. 2003

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“…Furthermore, any measurement will also include areas of necrosis that can bias the results to falsely low values. An alternative method is the immunohistochemical assessment of bound nitroimadazoles, such as pimonidazole, injected prior to biopsy (Kennedy et al, 1997;Nordsmark et al, 2001). This requires an added intervention and, as yet, there are only limited data on their relationship with treatment outcome.…”

Section: Discussionmentioning

confidence: 99%

Glucose transporter-1 (GLUT-1): a potential marker of prognosis in rectal carcinoma?

et al. 2003

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The aim of the study is to evaluate the pattern and level of expression of glucose transporter-1 (GLUT-1) in rectal carcinoma in relation to outcome as a potential surrogate marker of tumour hypoxia. Formalin-fixed tumour sections from 43 patients with rectal carcinoma, who had undergone radical resection with curative intent, were immunohistochemically stained for GLUT-1. A mean of three sections per tumour (range 1 -12) were examined. Each section was semiquantitatively scored; 0, no staining; 1, o10%; 2, 10 -50%; 3, 450% and a score given for the whole section, the superficial (luminal) and deep (mural) part of the tumour. Staining was seen in 70% of tumours. Increased staining was noted adjacent to necrosis and ulceration. A diffuse and patchy pattern of staining, with and without colocalisation to necrosis was seen. Patients with high GLUT-1-expressing tumours (score 3 vs 0 -2) had a significantly poorer overall survival (P ¼ 0.041), which was associated with poorer metastasis-free survival with no difference in local control. No significant correlation was seen with other prognostic factors. There was a strong correlation between the score for the superficial and deep parts of the tumour (r ¼ 0.81), but a significant relationship with outcome was only found in the deep part (P ¼ 0.003 vs P ¼ 0.46). In conclusion, increased GLUT-1 expression in rectal tumours was an adverse prognostic factor and is worth further evaluation as a predictive marker of response to therapy.

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“…A more likely explanation for the discrepancy between the median pO 2 and the PET examination in the large tumours could be the simple fact that the pO 2 measurements tend to overestimate the degree of hypoxia in these large tumours, because some of the measurements are actually done in necrotic tissue. Interestingly, in a clinical study, the labelling of tumours of the cervix with pimonidazole was compared to the assessment of oxygen status with the Eppendo rf method and no direct correlation between the assays was found (37). N ordsmark et al also demontrated a low pimonidazole labelling for some of the tumours that had a relatively high fraction of hypoxic measurements with the Eppendorf method.…”

Section: Hypoxia Measurements and Volumementioning

confidence: 99%

Assessment of Hypoxia in Experimental Mice Tumours by [ 18 F] Fluoromisonidazole PET and pO 2 Electrode Measurements

et al. 2002

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Invasive oxygen measurements and pimonidazole labeling in human cervix carcinoma

Cited by 77 publications

References 20 publications

GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON

GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON

Glucose transporter-1 (GLUT-1): a potential marker of prognosis in rectal carcinoma?

Assessment of Hypoxia in Experimental Mice Tumours by [ 18 F] Fluoromisonidazole PET and pO 2 Electrode Measurements

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