Angiogenesis is an independent prognostic factor in malignant mesothelioma

Our plain-English summary of Angiogenesis is an independent prognostic factor in malignant mesothelioma, by J.G. Edwards, G. Cox, A. Andi, et al (British Journal of Cancer, 2001).

The study

• Authors: J.G. Edwards, G. Cox, A. Andi, J.L. Jones, R.A. Walker, D.A. Waller, K.J. O'Byrne
• Journal: British Journal of Cancer
• Published: 2001;85(6):863-8
• Cited by: 81 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Angiogenesis is essential for tumour growth beyond 1 to 2 mm in diameter. The clinical relevance of angiogenesis, as assessed by microvessel density (MVD), is unclear in malignant mesothelioma (MM). Immunohistochemistry was performed on 104 archival, paraffin-embedded, surgically resected MM samples with an anti-CD34 monoclonal antibody, using the Streptavidin-biotin complex immunoperoxidase technique. 93 cases were suitable for microvessel quantification. MVD was obtained from 3 intratumoural hotspots, using a Chalkley eyepiece graticule at x 250 power. MVD was correlated with survival by Kaplan-Meier and log-rank analysis. A stepwise, multivariate Cox model was used to compare MVD with known prognostic factors and the EORTC and CALGB prognostic scoring systems. Overall median survival from the date of diagnosis was 5.0 months. Increasing MVD was a poor prognostic factor in univariate analysis (P = 0.02). Independent indicators of poor prognosis in multivariate analysis were non-epithelial cell type (P = 0.002), performance status > 0 (P = 0.003) and increasing MVD (P = 0.01). In multivariate Cox analysis, MVD contributed independently to the EORTC (P = 0.006), but not to the CALGB (P = 0.1), prognostic groups. Angiogenesis, as assessed by MVD, is a poor prognostic factor in MM, independent of other clinicopathological variables and the EORTC prognostic scoring system. Further work is required to assess the prognostic importance of angiogenic regulatory factors in this disease.

Copyright 2001 Cancer Research Campaign http://www.bjcancer.com.

In plain English

This study from Leicester, UK, asked whether the density of small blood vessels in mesothelioma tumours (microvessel density, an indirect measure of angiogenesis, or new blood vessel growth) was linked to survival. The authors reviewed all malignant mesothelioma cases presenting to their institution since 1988. Of 140 cases, 93 could be stained and counted; their median survival from diagnosis was 5.0 months. Higher vessel density was linked to shorter survival when looked at alone (P = 0.02). In a combined analysis, three factors were each independently linked to poorer survival: non-epithelial cell type (hazard ratio 2.23, 95% CI 1.35 to 3.67), performance status above 0 (hazard ratio 2.10, 95% CI 1.29 to 3.43), and increasing vessel density, treated as a continuous count (hazard ratio 1.04, 95% CI 1.01 to 1.06, P = 0.01). Vessel density contributed independently to the EORTC scoring system but not the CALGB system. Recorded asbestos exposure (61 yes, 14 no) was not significantly associated with survival (P = 0.2). The authors concluded that angiogenesis, measured this way, is an independent poor prognostic factor in mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective study of archival surgical tumour samples, with case-note review, examining a prognostic factor for survival
• Who was studied: 140 cases of malignant mesothelioma presenting to the authors' department in Leicester, UK, since 1988. 104 had enough tumour material for counting, and 93 were successfully assessed (48 epithelioid, 18 mixed, 27 sarcomatoid).
• Exposure: Not an asbestos exposure study. The factor studied was tumour microvessel density: blood vessels were stained with an anti-CD34 antibody and counted with a Chalkley graticule in 3 tumour 'hot spots'. Asbestos exposure was recorded only as one background variable.
• Main results:
  • Median survival from histological diagnosis for the 93 cases was 5.0 months
  • Median Chalkley count (sum of 3 hot spots) in the 93 cases was 23 (range 13 to 29)
  • In the 93 cases, analysed one factor at a time, high microvessel density as a continuous variable was a poor prognostic factor (hazard ratio 1.03, 95% CI 1.01 to 1.05, P = 0.02)
  • In multivariate analysis, with microvessel density analysed as a continuous variable, the independent poor prognostic factors were non-epithelial cell type (hazard ratio 2.23, 95% CI 1.35 to 3.67, P = 0.002), performance status above 0 (hazard ratio 2.10, 95% CI 1.29 to 3.43, P = 0.003) and increasing microvessel density (hazard ratio 1.04, 95% CI 1.01 to 1.06, P = 0.01)
  • Increasing microvessel density contributed independently to the EORTC prognostic scoring system (P = 0.006) but not to the CALGB system (P = 0.1)
  • Microvessel density was significantly correlated with platelet count (P = 0.048), but not with white cell count, haemoglobin or age
  • In single-factor analysis, recorded asbestos exposure (61 yes, 14 no) was not significantly associated with survival (hazard ratio 0.70, 95% CI 0.38 to 1.26, P = 0.2)
• The authors' conclusion: The authors concluded that increased microvessel density, as assessed by Chalkley counting, is an independent prognostic factor in malignant mesothelioma and adds to the EORTC scoring system. They said further work is needed on angiogenic regulatory factors.
• Limitations the authors state:
  • Accurate IMIG TNM stage could not be derived for this cohort. Pathological verification of stage was available in only 20 (21.5%) patients.
  • 36 cases had insufficient material and 11 could not be counted because of stromal staining. A further 10 cases were excluded from multivariate analysis because of missing case-note data.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Angiogenesis, Mesothelioma, Immunohistochemistry, CD34, Monoclonal Antibody, Median Overall Survival, Prognosis, Multivariate Analysis.

Related studies

• Tumor necrosis correlates with angiogenesis and is a predictor of poor prognosis in malignant mesothelioma — J.G. Edwards, D.E. Swinson, et al. (2003)
• Brain-derived neurotrophic factor, a new soluble biomarker for malignant pleural mesothelioma involved in angiogenesis — P. Smeele, S.M. d'Almeida, et al. (2018)
• Induction of angiogenesis by intraperitoneal injection of asbestos fibers — R.M. Branchaud, J.L. MacDonald, et al. (1989)
• Validation of prognostic factors in malignant pleural mesothelioma: a retrospective analysis of data from patients seeking compensation from the New South Wales Dust Diseases Board — S.C. Kao, J. Vardy, et al. (2013)
• Prognostic factors in malignant pleural mesothelioma — B. Davidson (2015)
• The relationship between angiogenesis and the immune response in carcinogenesis and the progression of malignant disease — K.J. O'Byrne, A.G. Dalgleish, et al. (2000)

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