CD74: a new prognostic factor for patients with malignant pleural mesothelioma

Our plain-English summary of CD74: a new prognostic factor for patients with malignant pleural mesothelioma, by C. Otterstrom, A. Soltermann, I. Opitz, et al (British Journal of Cancer, 2014).

The study

• Authors: C. Otterstrom, A. Soltermann, I. Opitz, E. Felley-Bosco, W. Weder, R.A. Stahel, F. Triponez, J.H. Robert, V. Serre-Beinier
• Journal: British Journal of Cancer
• Published: 2014;110(8):2040-6
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The pro-inflammatory cytokine migration inhibitory factor (MIF) and its receptor CD74 have been proposed as possible therapeutic targets in several cancers. We studied the expression of MIF and CD74 together with calretinin in specimens of malignant pleural mesothelioma (MPM), correlating their expression levels with clinico-pathologic parameters, in particular overall survival (OS).

Methods: Migration inhibitory factor, CD74, and calretinin immunoreactivity were investigated in a tissue microarray of 352 patients diagnosed with MPM. Protein expression intensities were semiquantitatively scored in the tumour cells and in the peritumoral stroma. Markers were matched with OS, age, gender, and histological subtype.

Results: Clinical data from 135 patients were available. Tumour cell expressions of MIF and CD74 were observed in 95% and 98% of MPM specimens, respectively, with a homogenous distribution between the different histotypes. CD74 (P<0.001) but not MIF overexpression (P=0.231) emerged as an independent prognostic factor for prolonged OS. High expression of tumour cell calretinin correlated with the epithelioid histotype and was also predictive of longer OS (P<0.001). When compared with previously characterised putative epithelial-to-mesenchymal transition markers, CD74 correlated positively with tumoral PTEN and podoplanin expressions, but was inversely related with periostin expression.

Conclusions: High expression of CD74 is an independent prognostic factor for prolonged OS in mesothelioma patients.

In plain English

This Swiss study examined archived tumour tissue, mostly from autopsies, from 352 patients with malignant pleural mesothelioma diagnosed between 1975 and 2004. The authors stained it for migration inhibitory factor (MIF), its receptor CD74, and calretinin. MIF was found in tumour cells of 95% of specimens and CD74 in 98%, at similar levels across subtypes; calretinin was highest in epithelioid tumours. Survival was analysed in 135 patients with clinical data. Median overall survival was 8.2 months (95% CI 5.6 to 10.9; 45 patients) with low CD74, 14.0 months (9.4 to 18.5; 49 patients) with medium and 14.7 months (10.1 to 19.3; 39 patients) with high CD74. After adjusting for age, gender and other markers, medium/high versus none/low CD74 had a hazard ratio of 0.72 (95% CI 0.57 to 0.89). MIF levels were not linked to survival; higher calretinin was. The article reports marker levels as independent of known asbestos exposure, without details. The authors concluded that CD74 is an independent prognostic factor. They noted the retrospective clinical data limited correlating marker levels with tumour stage, therapy and overall survival.

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 multicentre tissue study (tissue microarray immunohistochemistry) with survival analysis (Kaplan–Meier and Cox regression)
• Who was studied: Tumour specimens from 352 patients with malignant pleural mesothelioma diagnosed 1975–2004, from the archives of the Zurich Pneumoconiosis Research Group, Switzerland (77% autopsy, 23% biopsy). Histology: 123 epithelioid, 46 sarcomatoid, 183 biphasic. Clinical data were available for 135 patients (94% male, median age 63 years, range 40–93).
• Exposure: The study measured tumour and stromal expression of the proteins MIF, CD74 and calretinin. Asbestos exposure was not analysed in detail and no fiber types are given. The article states only that tumour marker expression was independent of known asbestos exposure.
• Main results:
  • MIF was found in tumour cells of 334 of 352 specimens (95%).
  • CD74 was found on tumour cells in 98% of specimens.
  • MIF and CD74 levels in tumour cells were similar across epithelioid, sarcomatoid and biphasic mesothelioma.
  • Calretinin levels were higher in epithelioid tumours (median histoscore 695, n=123) than in mixed (median 270, n=183) and sarcomatoid tumours (median 0, n=46).
  • Among the 135 patients with clinical data, those with low tumour CD74 (n=45) had a median overall survival of 8.2 months (95% CI 5.6–10.9). This compared with 14.0 months (95% CI 9.4–18.5; n=49 per Figure 3) for medium and 14.7 months (95% CI 10.1–19.3; n=39 per Figure 3) for high CD74 (p less than 0.001).
  • In multivariate Cox analysis adjusted for gender, age, calretinin and MIF, medium/high versus none/low tumour CD74 had a hazard ratio of 0.72 (95% CI 0.57–0.89), P=0.003.
  • MIF expression in tumour cells did not correlate with survival (log-rank P=0.231). In the multivariate analysis, medium/high MIF had a hazard ratio of 1.02 (95% CI 0.83–1.26), P=0.8.
  • Patients with no tumour calretinin (n=28) had a median overall survival of 6.5 months (95% CI 4.0–8.9). This compared with 11.3, 13.5 and 16.5 months for low, medium and high calretinin. In the multivariate analysis, medium/high calretinin had a hazard ratio of 0.79 (95% CI 0.65–0.96), P=0.016.
  • Histological subtype was left out of the main model. When it was included, calretinin was no longer an independent prognostic factor, but the effect of CD74 did not change.
  • Expression of the markers in the surrounding stroma cells did not correlate with survival.
  • CD74 correlated positively with calretinin, MIF, D2-40 (podoplanin) and PTEN, and negatively with periostin.
• The authors' conclusion: The authors concluded that MIF and its receptor CD74 are expressed in malignant pleural mesothelioma and that CD74 is an independent prognostic factor. They suggested these markers could help characterise tumour types and identify patients with a worse prognosis.
• Limitations the authors state:
  • The clinical data were retrospective, which limited correlation of marker expression with tumour stage, therapy and overall survival.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Cytokine, Calretinin, Overall Survival, Histological Subtype, Epithelioid, Podoplanin (D2-40), Mesothelioma.

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