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      Bony metastases from breast cancer - a study of foetal antigen 2 as a blood tumour marker

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      Author(s): 1 , , 2 , 1
      Publication date (Electronic):
      Journal: World Journal of Surgical Oncology
      Publisher: BioMed Central

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          Abstract

          Background

          Foetal antigen 2 (FA-2), first isolated in the amniotic fluid, was shown to be the circulating form of the aminopropeptide of the alpha 1 chain of procollagen type I. Serum concentrations of FA-2 appeared to be elevated in a number of disorders of bone metabolism. This paper is the first report of its role as a marker of bone metabolism in metastatic breast cancer.

          Methods

          Serum FA-2 concentrations were measured by radioimmunoassay in 153 women with different stages of breast cancer and in 34 normal controls.

          Results

          Serum FA-2 was significantly elevated in women with bony metastases ( p < 0.015). Its levels were not significantly different among women with non-bony metastases, with non-metastatic disease, as well as among normal controls.

          Conclusions

          FA-2 is a promising blood marker of bone metabolism. Further studies to delineate its role in the diagnosis and management of bony metastases from breast cancer are required.

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          Most cited references12

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          Tumour marker measurements in the diagnosis and monitoring of breast cancer.

          Nathan Graves, Elizabeth J. Robertson, Jo L K Cheung (2000)
          Elevation of established blood tumour markers correlates with the stage of breast cancer. The major role of current blood markers is therefore in the diagnosis and monitoring of metastatic disease. A combination of markers is better than a single marker with the most widely adopted combination being CEA and one MUC1 mucin, commonly detected as either CA15.3 or CA27.29. Tumour marker measurement is now used as a complementary test in the diagnosis of symptomatic metastases. In the monitoring of therapeutic response to both endocrine and cytotoxic therapies in advanced disease, biochemical assessment using blood markers not only correlates with conventional UICC criteria but has a lot of advantages which make it a potentially superior way of assessment. In this regard, CA15.3, CEA and ESR are the best validated combination. Studies are ongoing to evaluate the use of sequential blood tumour marker measurements in the follow-up of patients after treatment for their primary breast cancer, in terms of both early detection and early therapeutic intervention. Further randomized studies are also required to ascertain that marker-directed therapy is superior to the current practice for metastatic disease. In line with clinical studies, intensive laboratory work is being carried out to optimize the use of blood markers in advanced disease as well as to exploit their use in screening and diagnosis of early primary breast cancer.
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            Serum concentrations of type I collagen carboxyterminal telopeptide (ICTP) and type I procollagen carboxy-and aminoterminal propeptides (PICP, PINP) as markers of metastatic bone disease in breast cancer.

            R Tähtelä, E Thölix (2015)
            The most abundant protein in bone is type I collagen. During type I collagen formation two extension peptides from both ends of the procollagen molecule, carboxy- and aminoterminal propeptides (PICP and PINP), are liberated in equimolar concentrations into the circulation. Type I collagen carboxyterminal telopeptide (ICTP) is formed during bone collagen breakdown and is liberated into the circulation. Serum concentration of the propeptides reflect bone formation, and the concentration of the telopeptide, bone resorption. We evaluated the usefulness of these bone remodelling markers in diagnosing and monitoring metastatic bone disease in breast cancer patients. Serum concentrations of ICTP, PICP and PINP were measured and the PICP/PINP-ratio calculated in 25 patients with bone metastases, 12 patients without metastases and their age matched healthy controls. S-ICTP and S-PINP were significantly higher in metastatic patients (p = 0.0001 and 0.02 respectively), and the S-PICP/PINP-ratio lower (p = 0.002) than in controls. S-PICP in metastatic patients did not differ significantly from that of controls. ICTP values in patients without metastases also differed from those of controls (p = 0.01). The clinical sensitivity for diagnosing metastatic bone disease was 56% for ICTP, 24% for PICP, 30% for PINP and 52% for PICP/PINP ratio. The clinical specifities were 93%, 100%, 98% and 91% respectively. During follow-up the changes in the marker values were parallel to the behaviour of the disease. We conclude that these markers alone are not sensitive enough for diagnosis, but they seem to be of use in detecting bone metastases and monitoring the activity of bone disease.
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              Two fetal antigens (FA-1 and FA-2) and endometrial proteins (PP12 and PP14) isolated from amniotic fluid; preliminary observations in fetal and maternal tissues.

              B Teisner, J Grudzinskas, Fae Chapman … (1988)
              Rabbit antihuman antibodies were derived by the injection of fractions of second trimester amniotic fluid known to contain proteins of endometrial/decidual origin. Using standard separation and absorption procedures, two antibody preparations were generated which demonstrated specificities against two and three proteins, respectively, in line immunoelectrophoresis and crossed immunoelectrophoresis. Analysis against proteins of fetal, maternal, endometrial and placental origin revealed that the bispecific antiserum reacted only with placental protein 14 (PP14; also known as progestagen-dependent endometrial protein, PEP) and one other hitherto undescribed antigen referred to as Fetal Antigen 1 (FA-1) molecular mass 60 kDa; electrophoretic mobility: slow; alpha 1-alpha 2; fast, albumin. The trispecific antiserum demonstrated specifities against placental protein 12 (PP12), alpha-fetoprotein (AFP) and another previously undescribed antigen referred to as Fetal Antigen 2 (FA-2) molecular mass 35 and 140 kDa; electrophoretic mobility: albumin. Following purification, monospecific antisera against each of these proteins (with the exception of AFP) were derived in new rabbits. Maternal and fetal blood, amniotic fluid and aqueous extracts from endometrial/decidual and placental tissues were analysed in rocket immunoelectrophoresis using these antisera to examine the distribution in these tissues. The analyses demonstrated a pattern of distribution typical for proteins of endometrial/decidual origin in these compartments in the case of PP12 and PP14, but suggested that the primary source of origin of FA-1 and FA-2 may be the fetus.
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                Author and article information

                Journal
                Journal ID (nlm-ta): World J Surg Oncol
                Title: World Journal of Surgical Oncology
                Publisher: BioMed Central
                ISSN (Electronic): 1477-7819
                Publication date Collection: 2010
                Publication date (Electronic): 13 May 2010
                Volume: 8
                Page: 38
                Affiliations
                [1 ]Division of Breast Surgery, University of Nottingham, Nottingham, UK
                [2 ]Williamson Laboratory, St Bartholomew's Hospital, London, UK
                Article
                Publisher ID: 1477-7819-8-38
                DOI: 10.1186/1477-7819-8-38
                PMC ID: 2879255
                PubMed ID: 20465790
                SO-VID: 32755bfb-8151-4eeb-8cca-0c22d54d109f
                Copyright © Copyright ©2010 Cheung et al; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 16 March 2010
                Date accepted : 13 May 2010
                Categories
                Subject: Research

                ScienceOpen disciplines: Surgery
                Data availability:
                ScienceOpen disciplines: Surgery

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