Expression of neural cell adhesion molecule L1 (CD171) in neuroectodermal and other tumors: An immunohistochemical study of 5155 tumors and critical evaluation of CD171 prognostic value in gastrointestinal stromal tumors

Our plain-English summary of Expression of neural cell adhesion molecule L1 (CD171) in neuroectodermal and other tumors: An immunohistochemical study of 5155 tumors and critical evaluation of CD171 prognostic value in gastrointestinal stromal tumors, by S. Inaguma, Z. Wang, J.P. Lasota, et al (Oncotarget, 2016).

The study

• Authors: S. Inaguma, Z. Wang, J.P. Lasota, M.M. Miettinen
• Journal: Oncotarget
• Published: 2016;7(34):55276-55289
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The neural cell adhesion molecule L1 (CD171) is a multidomain type 1 membrane glycoprotein of the immunoglobulin superfamily important in the nervous system development, kidney morphogenesis, and maintenance of the immune system. Recent studies reported CD171 expression being associated with adverse clinical outcome in different types of cancer and there has been a growing interest in targeting this cell membrane molecule on neoplastic cells by chimeric antigen receptor redirected T lymphocytes or specific antibodies. Nevertheless, conflicting results regarding the prognostic value of CD171 expression in renal cell carcinomas and gastrointestinal stromal tumors were published. In this study, CD171 expression was immunohistochemically analyzed in 5155 epithelial, mesenchymal, melanocytic, and lymphohematopoietic tumors to assess its utility in diagnostic pathology and to pinpoint potential targets for CD171-targeting therapy. A newly developed anti-CD171 rabbit monoclonal antibody, clone 014, was selected from the panel of commercially available CD171 antibodies. Immunohistochemistry was performed using Leica Bond Max automation and multitumor blocks containing up to 60 tumor samples. CD171 was constitutively and strongly expressed in neuroectodermal tumors such as schwannoma, neuroblastoma, and paraganglioma, whereas other mesenchymal tumors including schwannoma mimics showed only rarely CD171 positivity. Frequent CD171-expression was also detected in ovarian serous carcinoma, malignant mesothelioma, and testicular embryonal carcinoma. CD171 immunohistochemistry may have some role in immunophenotypic differential diagnosis of neurogenic tumors and pinpointing potential candidates for anti-CD171 therapy. Though, because of its rare expression and lack of predictive value, CD171 is neither a diagnostic nor prognostic marker for gastrointestinal stromal tumors.

In plain English

This laboratory study, by researchers at the US National Cancer Institute, tested 5155 anonymized tumor samples of many kinds for a protein called CD171. The researchers used tissue staining (immunohistochemistry) with a rabbit antibody, clone 014, chosen after comparison with two other antibodies. The study did not examine asbestos exposure. Malignant mesothelioma was among the tumor types tested: 128 of 183 (69.9%) were positive. The article does not say whether these were pleural or peritoneal. Positivity was nearly universal in schwannomas outside the digestive tract (74 of 74) and within it (36 of 38), in neuroblastoma (29 of 29) and in paraganglioma (65 of 67). It was frequent in ovarian serous carcinoma (84 of 97) and testicular embryonal carcinoma (21 of 35). Only 20 of 1300 gastrointestinal stromal tumors (1.5%) were positive, and no significant link with outcome was found in conventional stomach cases. The authors concluded that CD171 staining may help diagnose neural tumors, and they proposed strongly positive tumor types as possible targets for future anti-CD171 treatment. They also concluded that CD171 is not useful for diagnosing gastrointestinal stromal tumors or predicting their outcome.

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 (immunohistochemical) study of archived tumor samples; a preliminary comparison of three CD171 antibodies; survival analysis in conventional gastric GIST patients
• Who was studied: 5155 anonymized tumor samples (epithelial, mesenchymal, melanocytic and lymphohematopoietic), placed on multitumor blocks, including 183 malignant mesotheliomas and 1300 gastrointestinal stromal tumors; also a panel of normal tissues. The article does not state where or when the tumors were collected.
• Exposure: No asbestos or other environmental or occupational exposure was studied. What was measured was staining for the protein CD171 with rabbit monoclonal antibody clone 014.
• Main results:
  • Malignant mesothelioma: 128 of 183 tumors (69.9%) were CD171-positive. The site (pleural or peritoneal) is not given.
  • Neural tumors were almost always positive. Schwannomas outside the gastrointestinal tract were positive in 74 of 74 cases, and gastrointestinal schwannomas in 36 of 38 (94.7%). Neuroblastoma was positive in 29 of 29 and paraganglioma in 65 of 67.
  • Ovarian serous carcinoma was positive in 84 of 97 cases (86.6%) and testicular embryonal carcinoma in 21 of 35 (60.0%).
  • Gastrointestinal stromal tumors: 20 of 1300 (1.5%) were positive, mostly weakly. There was no significant correlation between CD171 positivity and outcome in conventional gastric GIST patients.
  • Colorectal adenocarcinoma: CD171 was positive in 64.2% of mismatch repair-preserved tumors (n=187) versus 21.7% of mismatch repair-deficient tumors (n=23), p less than 0.01.
• The authors' conclusion: The authors concluded that CD171 staining with the new rabbit antibody may assist diagnosis of neural or neuroectodermal tumors. They proposed CD171-highly expressing tumors as potential targets for anti-CD171 therapy. They also concluded that CD171 is not useful for GIST diagnosis or prognosis.
• Limitations the authors state:
  • Survival analysis was done only in conventional gastric GIST patients because there were too few CD171-positive GISTs from other sites.
  • The authors could not explain why their GIST positivity rate differed from earlier reports.

Topics

Medical terms in this study, explained in our Lexicon: Glycoprotein, Carcinoma, Pathology, Monoclonal Antibody, Immunohistochemistry, Mesenchymal Tumor, Ovarian Serous Carcinoma, Mesothelioma.

Related studies

• Insulin-like growth factor II messenger RNA-binding protein 3 expression in gastrointestinal mesenchymal tumors — H. Yamamoto, K. Arakaki, et al. (2014)
• Primary omental gastrointestinal stromal tumor (GIST) — T. Todoroki, T. Sano, et al. (2007)
• NCAM (neural cell adhesion molecules) expression in malignant mesotheliomas — S. Lantuéjoul, M.H. Laverrière, et al. (2000)
• Comprehensive immunohistochemical study of mesothelin (MSLN) using different monoclonal antibodies 5B2 and MN-1 in 1562 tumors with evaluation of its prognostic value in malignant pleural mesothelioma — S. Inaguma, Z. Wang, et al. (2017)
• Nuclear Brachyury Expression Is Consistent in Chordoma, Common in Germ Cell Tumors and Small Cell Carcinomas, and Rare in Other Carcinomas and Sarcomas: An Immunohistochemical Study of 5229 Cases — M. Miettinen, Z. Wang, et al. (2015)
• Epithelial Cell Adhesion Molecule (EpCAM) Expression in Human Tumors: A Comparison with Pan-Cytokeratin and TROP2 in 14,832 Tumors — A. Menz, N. Lony, et al. (2024)

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