NCAM (neural cell adhesion molecules) expression in malignant mesotheliomas

Our plain-English summary of NCAM (neural cell adhesion molecules) expression in malignant mesotheliomas, by S. Lantuéjoul, M.H. Laverrière, N. Sturm, et al (Human Pathology, 2000).

The study

• Authors: S. Lantuéjoul, M.H. Laverrière, N. Sturm, D. Moro, G. Frey, C. Brambilla, E. Brambilla
• Journal: Human Pathology
• Published: 2000;31(4):415-21
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Neural cell adhesion molecules (NCAM) are adhesion molecules expressed by neural and neuroendocrine tumors and a few biphasic tumors such as synovialosarcomas and breast phyllode tumors. To investigate NCAM expression in mesotheliomas, we studied 26 cases of epithelioid (n = 12), biphasic (n = 11), and sarcomatoid (n = 3) malignant mesotheliomas (MM), in comparison with normal mesothelium, and 50 primary non-small cell lung carcinomas (NSCLC) (25 adenocarcinomas [ADC] and 25 squamous cell carcinomas [SCC]), using electron microscopy as a gold standard for recognition of MM. NCAM reactivity using 123C3 antibody was compared with that of NE markers such as chromogranin A and synaptophysin. Although normal mesothelium remains negative, NCAM was expressed in 19 of 26 MM (73%) with a membranous staining on frozen or paraffin sections. In 6 of 12 epithelioid MM, the tumor cells expressed NCAM, whereas in 5 cases stromal fibroblasts showed a strong but focal staining. In 11 biphasic MM, 4 presented an NCAM reactivity of both epithelioid and spindle cell components, whereas in 7, only fusiform component was NCAM positive. Two of 3 sarcomatoid MM showed an NCAM expression. Chromogranin expression was never seen, whereas synaptophysin was noticed in 2 cases. No case of NSCLC showed membranous 123C3 staining, whereas 2 ADC weakly expressed synaptophysin. We conclude that NCAM expression in MM is reminiscent of its expression in mesoderm during fetal life and consistent with that reported in other biphasic tumors. These data show that NCAM expression occurs in 73% of MM, highly exceeding that observed in lung cancer.

In plain English

This laboratory study from Grenoble, France, tested whether malignant mesothelioma tumors carry a protein called NCAM (neural cell adhesion molecule), which might help pathologists tell mesothelioma apart from other cancers. The authors stained surgical samples from 26 patients with malignant mesothelioma (12 epithelioid, 11 biphasic, 3 sarcomatoid). All but one were pleural; one patient had both pleural and peritoneal tumors. They compared these with normal pleural tissue and 50 lung cancers (25 adenocarcinomas, 25 squamous cell carcinomas). Fourteen of the 26 mesothelioma patients had a history of asbestos exposure, and the article did not report results by exposure. Using the 123C3 antibody, NCAM was found in 19 of 26 mesotheliomas (73%) on frozen tissue sections but in only 6 of 26 (23%) on paraffin sections. Normal mesothelial cells were negative. Among the lung cancers, 4 of 50 (8%) showed NCAM (2 cases) or synaptophysin (2 cases). The authors proposed the antibody as a possible positive marker for epithelioid or biphasic mesothelioma versus metastatic adenocarcinoma. Because of its moderate sensitivity on paraffin sections, they concluded it does not reach the practical value of calretinin, cytokeratin 5/6 and thrombomodulin.

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 pathology study (immunohistochemistry on tumor tissue, with electron microscopy to confirm the diagnosis of mesothelioma)
• Who was studied: 26 malignant mesotheliomas (12 epithelioid, 11 biphasic, 3 sarcomatoid) from surgical specimens at the Thoracic Surgery Department, Grenoble, France. 18 of the 26 were men aged 46 to 78 (mean 67). All were primary pleural except 1 patient with both pleural and peritoneal tumors. Comparison groups: normal pleural tissue and 50 primary lung carcinomas (25 adenocarcinomas, 25 squamous cell carcinomas; 45 of 50 patients male).
• Exposure: Not the subject of the study. 14 of 26 mesothelioma patients had a history of asbestos exposure, based on occupational context or mineral analysis of a lung sample. 3 patients were not investigated. No fiber type is named. The laboratory exposure was staining with the NCAM antibody 123C3, plus chromogranin A and synaptophysin.
• Main results:
  • All mesotheliomas: NCAM expression in 19 of 26 (73%) on frozen sections (6 epithelioid, 11 biphasic, 2 sarcomatoid) and in 6 of 26 (23%) on paraffin sections.
  • Epithelioid mesothelioma: 6 (50%) of 12 were positive on frozen sections, with 30% to 60% of cells showing membranous staining. Only 3 were positive on paraffin sections.
  • Epithelioid mesothelioma: in 5 cases, 10% to 70% of stromal fibroblasts stained. In 4 of these 5 there was no staining of the tumor's epithelial cells.
  • Biphasic mesothelioma, frozen sections: 4 of 11 showed staining in 10% of epithelial cells. The spindle-cell (fusiform) component was positive in all 11, in 10% to 80% of cells.
  • Sarcomatoid mesothelioma: 2 of 3 were positive on frozen sections, compared with 1 on paraffin sections.
  • Neuroendocrine markers in mesothelioma: synaptophysin was seen in 2 epithelioid cases (10% to 30% of cells). Chromogranin A was negative in all histological types.
  • Normal mesothelial cells showed no NCAM, chromogranin or synaptophysin.
  • Lung cancers: 4 of 50 (8%) expressed NCAM (2 cases: 1 squamous cell carcinoma on frozen sections, 1 adenocarcinoma on paraffin sections) or synaptophysin (2 adenocarcinomas). Chromogranin A was never expressed.
• The authors' conclusion: The authors concluded that NCAM is expressed in all histological subtypes of malignant mesothelioma and that this should be recognized to avoid misdiagnosis. They proposed the 123C3 antibody as a positive marker for epithelioid or biphasic mesothelioma versus metastatic adenocarcinoma. Because of its moderate sensitivity on paraffin sections, they judged it short of the practical value of calretinin, CK 5/6 and thrombomodulin. In sarcomatoid mesothelioma they found it of little interest, with cytokeratin remaining the gold standard. They also suggested that NCAM expression in the embryonic mesoderm could explain its expression in mesothelioma.
• Limitations the authors state:
  • Staining on paraffin (formalin-fixed) sections was weaker and uneven, detecting NCAM in only 23% of mesotheliomas versus 73% on frozen sections.
  • The prognostic significance of NCAM expression in mesothelioma has not been shown.
  • NCAM expression could lead to a misdiagnosis of neuroendocrine carcinoma.

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: Malignant Mesothelioma, Biphasic Mesothelioma, Mesothelioma, Epithelioid, Sarcomatoid, Mesothelium, Carcinoma, Adenocarcinoma.

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