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 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.
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Maho
M
Nagata
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Research Center for Inflammation and Regenerative Medicine, Doshisha University, Kyoto, Japan.
Takahiro
T
Nakamura
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Chie
C
Sotozono
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Tsutomu
T
Inatomi
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Norihiko
N
Yokoi
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Shigeru
S
Kinoshita
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D066246:ErbB Receptors / Q000096:biosynthesis; D005134:Eye Neoplasms / Q000378:metabolism* / Q000473:pathology; D005136:Eye Proteins / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007633:Keratins / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D005136:Eye Proteins; C484445:LRIG1 protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D007633:Keratins; C512478:EGFR protein, human; D066246:ErbB Receptors