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The presence of carboxypeptidase-M in tumour cells signifies epidermal growth factor receptor expression in lung adenocarcinomas

The coexistence predicts a poor prognosis regardless of EGFR levels

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Abstract

Purpose

Carboxypeptidase-M (CPM) is a membrane-bound peptidase that metabolizes peptides, and is present in pneumocytes. CPM hydrolyses the C-terminal arginine of epidermal growth factor (EGF) resulting in des-Arg53-EGF which binds to the EGF receptor (EGFR) with an equal or greater affinity than native EGF. Therefore, this study focused on the possible presence of CPM in human lung adenocarcinomas (ADC) and evaluated the relationship between CPM and EGFR by assessing the impact of expressions on patient clinical outcome.

Methods

This is a retrospective study of 110 patients who underwent resection of the primary tumour (92) or metastatic tissues (18) for treatment or diagnosis. Immunohistochemistry (IHC) for CPM and EGFR was made in serial sections using standard methods.

Results

This study demonstrates for the first time that 23.6% of ADCs express carboxypeptidase-M (26/110), mainly in membrane-bound forms. The amounts and the extent of CPM within tumours vary from low levels to obviously overexpressed forms. The immunohistochemical positivity (+) for CPM in ADCs negatively correlated with disease survival. In addition, 80% of CPM+ adenocarcinomas (21/26) showed a coexpression with EGFR suggesting a high prevalence for coexistence. The follow up data indicated a significantly shorter 5-year survival time for patients with CPM+–EGFR+ (double-positive) tumours compared to those harbouring neoplasias negative for both proteins (9.5 vs. 60.4% survivals, P < 0.001).

Conclusion

The fact that CPM+ ADCs often co-express with EGFR suggests a functional-regulatory link between these proteins which might have therapeutical consequences. The present novel data could lead to improved IHC tests in lung adenocarcinomas for EGFR expression.

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Acknowledgments

The authors are grateful to Drs. Ervin G. Erdös and Randal A. Skidgel (University of Illinois College of Medicine, Chicago, IL, USA) for suggestions and comments on the manuscript. The authors acknowledge the excellent technical assistance of Maria Besenyei. This work was supported by Feichtinger’s cancer foundation (Balazs Dezso) and the university research fund for Ph.D. program (Ioannis Tsakiris). A part of the morphological aspects of CPM immunostainings on lung cancers was presented (Balazs Dezso) at the 65th Annual Congress of the Hungarian Society of Pathologists held in Hajduszoboszlo (Hungary), 5–7 October, 2006.

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Authors and Affiliations

  1. Department of Pathology, University of Debrecen, Medical and Health Science Center, Nagyerdei krt. 98, 4032, Debrecen, Hungary

    Ioannis Tsakiris, Gyorgyike Soos, Zoltan Nemes & Balazs Dezso

  2. Department of Pulmonary Surgery, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary

    Sandor Sz. Kiss

  3. Department of Oncology, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary

    Csilla Andras & Janos Szantó

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  1. Ioannis Tsakiris
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  2. Gyorgyike Soos
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Correspondence to Balazs Dezso.

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Tsakiris, I., Soos, G., Nemes, Z. et al. The presence of carboxypeptidase-M in tumour cells signifies epidermal growth factor receptor expression in lung adenocarcinomas. J Cancer Res Clin Oncol 134, 439–451 (2008). https://doi.org/10.1007/s00432-007-0304-z

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  • DOI: https://doi.org/10.1007/s00432-007-0304-z

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