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LRIG1 as a Potential Novel Marker for Neoplastic Transformation in Ocular Surface Squamous Neoplasia

The leucine rich repeats and immunoglobulin-like protein 1 (LRIG1) is a newly discovered negative regulator of epidermal growth factor receptor (EGFR) and a proposed tumor suppressor. It is not universally downregulated in human cancers, and its role in neoplastic transformation and tumorigenesis is...

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Autores principales: Nagata, Maho, Nakamura, Takahiro, Sotozono, Chie, Inatomi, Tsutomu, Yokoi, Norihiko, Kinoshita, Shigeru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977825/
https://www.ncbi.nlm.nih.gov/pubmed/24709893
http://dx.doi.org/10.1371/journal.pone.0093164
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author Nagata, Maho
Nakamura, Takahiro
Sotozono, Chie
Inatomi, Tsutomu
Yokoi, Norihiko
Kinoshita, Shigeru
author_facet Nagata, Maho
Nakamura, Takahiro
Sotozono, Chie
Inatomi, Tsutomu
Yokoi, Norihiko
Kinoshita, Shigeru
author_sort Nagata, Maho
collection PubMed
description The leucine rich repeats and immunoglobulin-like protein 1 (LRIG1) is a newly discovered negative regulator of epidermal growth factor receptor (EGFR) and a proposed tumor suppressor. It is not universally downregulated in human cancers, and its role in neoplastic transformation and tumorigenesis is not well-documented. In this study, we show the expression of LRIG1 as a novel potential marker for neoplastic transformation in ocular-surface squamous neoplasia (OSSN). The following two groups were included in this study: 1) benign group (3 cases; 1 with papilloma and 2 with dysplasia) and 2) malignant group (3 cases with squamous cell carcinoma (SCC)). In both groups, immunofluorescence analysis was firstly performed for keratins 4, 12, 13, and 15 to characterize the state of differentiation, and for Ki67 to evaluate the proliferation activity. Subsequently, LRIG1 and EGFR expression was analyzed. Either keratin 4 and/or 13, both non-keratinized epithelial cell markers, were generally expressed in both groups, except for 1 severe SCC case. Keratin 15, an undifferentiated basal cell marker, was more strongly expressed in the malignant cases than in the benign cases. The Ki67 index was significantly higher (P<0.002) in the malignant group (33.2%) than in the benign group (10.9%). LRIG1 expression was limited to basal epithelial cells in normal corneal epithelial tissue. Interestingly, LRIG1 was expressed throughout the epithelium in all the benign cases. In contrast, its expression was limited or totally disappeared in the malignant cases. Inversely, EGFR staining was faintly expressed in the benign cases, yet strongly expressed in the malignant cases. Malignant tissue with proliferative potential presented EGFR overexpression and inverse downregulation of LRIG1, consistent with LRIG1 being a suppressor of neoplastic transformation by counteracting the tumor growth property of EGFR. Our findings indicate that downregulation of LRIG1 is possibly a novel potential marker of transformation and tumorigenesis in OSSN cases.
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spelling pubmed-39778252014-04-11 LRIG1 as a Potential Novel Marker for Neoplastic Transformation in Ocular Surface Squamous Neoplasia Nagata, Maho Nakamura, Takahiro Sotozono, Chie Inatomi, Tsutomu Yokoi, Norihiko Kinoshita, Shigeru PLoS One Research Article The leucine rich repeats and immunoglobulin-like protein 1 (LRIG1) is a newly discovered negative regulator of epidermal growth factor receptor (EGFR) and a proposed tumor suppressor. It is not universally downregulated in human cancers, and its role in neoplastic transformation and tumorigenesis is not well-documented. In this study, we show the expression of LRIG1 as a novel potential marker for neoplastic transformation in ocular-surface squamous neoplasia (OSSN). The following two groups were included in this study: 1) benign group (3 cases; 1 with papilloma and 2 with dysplasia) and 2) malignant group (3 cases with squamous cell carcinoma (SCC)). In both groups, immunofluorescence analysis was firstly performed for keratins 4, 12, 13, and 15 to characterize the state of differentiation, and for Ki67 to evaluate the proliferation activity. Subsequently, LRIG1 and EGFR expression was analyzed. Either keratin 4 and/or 13, both non-keratinized epithelial cell markers, were generally expressed in both groups, except for 1 severe SCC case. Keratin 15, an undifferentiated basal cell marker, was more strongly expressed in the malignant cases than in the benign cases. The Ki67 index was significantly higher (P<0.002) in the malignant group (33.2%) than in the benign group (10.9%). LRIG1 expression was limited to basal epithelial cells in normal corneal epithelial tissue. Interestingly, LRIG1 was expressed throughout the epithelium in all the benign cases. In contrast, its expression was limited or totally disappeared in the malignant cases. Inversely, EGFR staining was faintly expressed in the benign cases, yet strongly expressed in the malignant cases. Malignant tissue with proliferative potential presented EGFR overexpression and inverse downregulation of LRIG1, consistent with LRIG1 being a suppressor of neoplastic transformation by counteracting the tumor growth property of EGFR. Our findings indicate that downregulation of LRIG1 is possibly a novel potential marker of transformation and tumorigenesis in OSSN cases. Public Library of Science 2014-04-07 /pmc/articles/PMC3977825/ /pubmed/24709893 http://dx.doi.org/10.1371/journal.pone.0093164 Text en © 2014 Nagata et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Nagata, Maho
Nakamura, Takahiro
Sotozono, Chie
Inatomi, Tsutomu
Yokoi, Norihiko
Kinoshita, Shigeru
LRIG1 as a Potential Novel Marker for Neoplastic Transformation in Ocular Surface Squamous Neoplasia
title LRIG1 as a Potential Novel Marker for Neoplastic Transformation in Ocular Surface Squamous Neoplasia
title_full LRIG1 as a Potential Novel Marker for Neoplastic Transformation in Ocular Surface Squamous Neoplasia
title_fullStr LRIG1 as a Potential Novel Marker for Neoplastic Transformation in Ocular Surface Squamous Neoplasia
title_full_unstemmed LRIG1 as a Potential Novel Marker for Neoplastic Transformation in Ocular Surface Squamous Neoplasia
title_short LRIG1 as a Potential Novel Marker for Neoplastic Transformation in Ocular Surface Squamous Neoplasia
title_sort lrig1 as a potential novel marker for neoplastic transformation in ocular surface squamous neoplasia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3977825/
https://www.ncbi.nlm.nih.gov/pubmed/24709893
http://dx.doi.org/10.1371/journal.pone.0093164
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