Tumor necrosis correlates with angiogenesis and is a predictor of poor prognosis in malignant mesothelioma

Our plain-English summary of Tumor necrosis correlates with angiogenesis and is a predictor of poor prognosis in malignant mesothelioma, by J.G. Edwards, D.E. Swinson, J.L. Jones, et al (Chest, 2003).

The study

• Authors: J.G. Edwards, D.E. Swinson, J.L. Jones, S. Muller, D.A. Waller, K.J. O'Byrne
• Journal: Chest
• Published: 2003;124(5):1916-23
• Cited by: 90 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: Malignant mesothelioma (MM) is a fatal tumor of increasing incidence related to asbestos exposure. Microscopic tumor necrosis (TN) is a poor prognostic factor in solid tumors, but it has not been characterized in MM. We wished to evaluate the incidence of TN in MM and its correlations with clinicopathologic factors, angiogenesis, and survival.

Methods: TN was graded in 171 routine formalin-fixed, paraffin-embedded hematoxylin-eosin-stained tumor sections by two independent observers. Angiogenesis was assessed by the microvessel count (MVC) of CD34 immunostained sections. TN was correlated with survival by Kaplan-Meier and log-rank analysis, and stepwise, multivariate Cox models were used to compare TN with angiogenesis and established prognostic factors and prognostic scoring systems.

Results: TN was identified in 39 cases (22.8%) and correlated with low hemoglobin (p = 0.01), thrombocytosis (p = 0.04), and high MVC (p = 0.02). TN was a poor prognostic factor in univariate analysis (p = 0.008). Patients with TN had a median survival of 5.3 months vs 8.3 months in negative cases. Independent indicators of poor prognosis in multivariate analysis were nonepithelioid cell type (p = 0.0001), performance status > 0 (p = 0.007), and increasing MVC (p = 0.004) but not TN. TN contributed independently to the European Organisation for Research and Treatment of Cancer (EORTC) [p = 0.03] and to the Cancer and Leukemia Group B (CALGB) [p = 0.03] prognostic groups in respective multivariate Cox analyses.

Conclusions: TN correlates with angiogenesis and is a poor prognostic factor in MM. TN contributes to the EORTC and CALGB prognostic scoring systems.

In plain English

This study examined archived tumor slides and case notes from 171 people with malignant mesothelioma seen at a Leicester, UK, institution between 1988 and 2001. It did not measure asbestos exposure. Two observers, unaware of outcomes, checked routine slides for dead tumor tissue (tumor necrosis). Necrosis was found in 39 of the 171 cases (22.8%). Necrosis was associated with low hemoglobin, high platelet counts and a higher count of small tumor blood vessels, a measure of angiogenesis (new vessel growth). The 17 patients who died within 30 days of biopsy were left out of the survival analyses only. Among the rest, median survival was 158 days for the 34 patients with necrosis and 248 days for the 120 without. When several factors were analyzed together, necrosis was not an independent predictor of survival. Cell type, general physical condition (performance status) and blood vessel count were. Necrosis did add information to two existing prognostic scoring systems, EORTC and CALGB. The authors concluded that necrosis is a poor prognostic factor in mesothelioma. They noted they could not assess whether tumor size confounded this.

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: Review of archived diagnostic tumor slides and case notes from one institution (retrospective case series), with survival analysis
• Who was studied: 171 cases of malignant mesothelioma (MM) presenting to the authors' institution in Leicester, UK, from 1988 to 2001. The patients had been referred to the regional Department of Cardiothoracic Surgery.
• Exposure: Asbestos exposure was not assessed. The factor studied was microscopic tumor necrosis, graded 0 to 3 on routine hematoxylin-eosin tumor sections. It was compared with angiogenesis, measured as microvessel count on CD34-stained sections, and with clinical factors and survival.
• Main results:
  • Tumor necrosis was present in 39 of 171 cases (22.8%). There were 14 cases of grade 1, 14 of grade 2 and 11 of grade 3.
  • The two observers agreed, before reaching a consensus, in 161 patients (94.2%; Cohen statistic 0.85).
  • Tumor necrosis correlated with low hemoglobin, thrombocytosis (high platelet count) and high microvessel count.
  • No relationship was seen between tumor necrosis and cell type, performance status, weight loss or pleuritic chest pain.
  • The 17 patients who died within 30 days of diagnostic biopsy were excluded from the further survival analyses, to avoid bias from postoperative deaths.
  • Median survival was 248 days for the 120 included cases without tumor necrosis and 158 days for the 34 included cases with it (log-rank p 0.008).
  • Without tumor necrosis, 6-month survival was 62.1% (95% CI 53.4 to 70.9%) and 12-month survival was 34.5% (95% CI 25.8 to 43.3%). With tumor necrosis, the rates were 47.1% (95% CI 30.3 to 63.8%) and 15.9% (95% CI 3.3 to 28.6%).
  • Survival did not differ between the three grades of tumor necrosis.
  • In multivariate analysis, the independent predictors of poor survival were cell type, performance status and microvessel count. Tumor necrosis was not an independent predictor.
  • Among epithelioid cases who survived past 30 days, median survival was 384 days for the 70 without tumor necrosis and 158 days for the 22 with it.
  • Tumor necrosis contributed to both the CALGB and the EORTC prognostic scoring systems when analyzed with each in Cox multivariate analysis.
• The authors' conclusion: The authors concluded that the presence of tumor necrosis is a poor prognostic factor in malignant mesothelioma.
• Limitations the authors state:
  • The authors suggested that tumor necrosis may not have been an independent factor because relatively few cases had it.
  • A possible confounding association between necrosis and tumor mass could not be assessed.
  • The authors said sample bias could not be completely ruled out, particularly for the smaller biopsy specimens, although they judged sampling error unlikely to be relevant.

Topics

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

Medical terms in this study, explained in our Lexicon: Necrosis, Angiogenesis, Prognosis, Malignant Mesothelioma, Asbestos Exposure, CD34, Median Survival, Multivariate Analysis.

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