Molecular cloning of a cell-surface glycoprotein that can potentially discriminate mesothelium from epithelium: its identification as vascular cell adhesion molecule 1

Our plain-English summary of Molecular cloning of a cell-surface glycoprotein that can potentially discriminate mesothelium from epithelium: its identification as vascular cell adhesion molecule 1, by T. Yamada, J. Jiping, R. Endo, et al (British Journal of Cancer, 1995).

The study

• Authors: T. Yamada, J. Jiping, R. Endo, M. Gotoh, Y. Shimosato, S. Hirohashi
• Journal: British Journal of Cancer
• Published: 1995;71(3):562-70
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

It has long been a practical problem for surgical pathologists to distinguish mesothelium from epithelium in order to make a positive diagnosis of mesothelioma. In this study, we developed a new monoclonal antibody, designated MS-2761 (IgG1, k), against cultured non-neoplastic mesothelial cells. Immunohistochemistry and slot-blot analysis revealed that this monoclonal antibody reacted with 100% (12/12) of benign and malignant mesothelioma tissues and a mesothelioma cell line, but not with 99% (77/78) of epithelial tumour tissues and 97% (33/34) of epithelial tumour cell lines. A gene encoding the cell-surface antigen defined by this monoclonal antibody was isolated from a mesothelial cell cDNA library constructed with a mammalian cell expression vector through transfection of Cos-7 cells and immunoselection by panning. DNA sequencing and a database search revealed that the gene was identical to vascular cell adhesion molecule 1 (VCAM1, also referred to as INCAM110). The prominent VCAM1 transcript in mesothelium was 3.2 kb in size with seven Ig-like domains, in addition to a minor transcripts with six Ig-like domains. This monoclonal antibody potentially discriminates mesothelium from epithelium and may become a tool for differential diagnosis of mesothelioma.

In plain English

This laboratory study from Tokyo's National Cancer Center sought a marker to help pathologists tell mesothelioma from epithelial tumours, which can look alike. The authors made a new mouse antibody, MS-2761, by immunising mice with cultured non-neoplastic mesothelial cells. It reacted with primary mesothelial cell cultures from all six patients tested and with a mesothelioma cell line; 33 of 34 epithelial tumour cell lines did not react. In tissue samples it stained all 12 pleural mesotheliomas (five benign fibrous, seven malignant). Of 78 epithelial tumours, 77 were classed as negative and one small-cell lung cancer as positive; in one negative lung adenocarcinoma, fewer than 5% of tumour cells stained. It also stained blood vessel lining and the fibrous stroma of most epithelial tumours. Gene cloning identified the target as vascular cell adhesion molecule 1 (VCAM1). This was not a study of asbestos exposure; the authors report that no history of defined asbestos exposure was obtained for any mesothelioma case. The authors concluded that the antibody seems to have potential value for telling mesothelium from epithelium. They said a larger series of tumours is needed to confirm its specificity.

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: Laboratory study: development of a monoclonal antibody, tested by immunostaining of cultured cells and tumour tissues, followed by molecular cloning of the gene for the antigen it detects
• Who was studied: Non-neoplastic mesothelial cells from the omentum of six patients having stomach cancer surgery. A malignant mesothelioma cell line (NCC-MS-1) from a pleural effusion. Forty-two established cell lines. Tumour tissues from the surgical pathology files of the National Cancer Center Hospital, Tokyo: 12 mesotheliomas, 33 lung cancers, two metastatic lung tumours, ten stomach cancers, 23 breast cancers and ten ovarian tumours. Non-neoplastic tissues from autopsies of six individuals.
• Exposure: This was not a study of asbestos exposure. The tested agent was the laboratory antibody MS-2761. The authors report that no history of defined asbestos exposure was obtained for any of the mesothelioma cases.
• Main results:
  • The antibody was raised by injecting mice with cultured non-neoplastic mesothelial cells. MS-2761 then reacted with all 6 of 6 primary cultures of non-neoplastic mesothelial cells from the omentum and with the one mesothelioma cell line tested (1 of 1).
  • Epithelial tumour cell lines: 33 of 34 were not reactive. The exception was the hepatoma cell line NCC-Li2l. MS-2761 also reacted with one of two endothelial cell lines (HUVEC).
  • Mesothelioma tissues: all 12 pleural mesothelioma cases stained. These were 5 of 5 benign fibrous, 1 of 1 malignant epithelioid, 1 of 1 malignant fibrous and 5 of 5 malignant biphasic. Staining of fibrous mesothelioma and of the sarcomatous component was relatively faint compared with epithelioid mesothelioma.
  • Epithelial tumour tissues: 77 of 78 were classed as negative. The one positive case was a small-cell lung cancer (1 of 6 small-cell lung cancers), from a patient who had extensive chemotherapy before surgery. Its staining pattern was not seen in epithelioid mesothelioma.
  • Focal staining in one lung adenocarcinoma classed as negative: fewer than 5% of tumour cells at the tumour's edge showed membranous staining.
  • Although the cancer cells did not stain, the fibrous stroma (supporting tissue) of most epithelial tumours stained strongly.
  • Normal autopsy tissues: staining was seen in mesothelium, vascular endothelium, epithelium of Bowman's capsule in the kidney, Kupffer cells of the liver, dendritic fibres of lymph follicles and adrenal cortex cells.
  • Gene cloning and sequencing identified the antigen as vascular cell adhesion molecule 1 (VCAM1).
  • Non-neoplastic mesothelial cells mainly expressed a 3.2 kb VCAM1 transcript. Expression in the mesothelioma cell line NCC-MS-1 was much lower than in non-neoplastic mesothelial cells.
• The authors' conclusion: The authors concluded that the antibody seems to have potential value for distinguishing mesothelium from epithelium, and may become a tool for the differential diagnosis of mesothelioma.
• Limitations the authors state:
  • A larger series of tumours with different histological patterns needs to be studied to confirm the antibody's specificity.
  • The antibody also reacts with cancer stromal fibroblasts. In fibrous mesothelioma and the sarcomatous component of biphasic mesothelioma, tumour cell staining could not be told apart from staining of activated fibroblasts. Reactivity therefore does not rule out a mesenchymal origin for benign fibrous mesothelioma.

Topics

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

Medical terms in this study, explained in our Lexicon: Glycoprotein, Mesothelium, Epithelium, Mesothelioma, Monoclonal Antibody, Mesothelial Cells, Immunohistochemistry, Differential Diagnosis.

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