Elsevier

Ophthalmology

Volume 128, Issue 5, May 2021, Pages 765-778
Ophthalmology

Original Article
Usefulness of PAX8 Immunohistochemistry in Adult Intraocular Tumor Diagnosis

https://doi.org/10.1016/j.ophtha.2020.09.033Get rights and content

Purpose

To evaluate the distribution of the PAX8 transcription factor protein in ocular tissues and to investigate if immunohistochemical stains for this biomarker are useful in the diagnosis of intraocular tumors.

Design

Observational case series.

Participants

Excision and cytologic analysis specimens of 6 ciliary body epithelial neoplasms, 2 iris epithelial neoplasms, 3 retinal pigment epithelial neoplasms, 3 intraocular medulloepitheliomas, 15 uveal melanomas, and 5 uveal melanocytomas.

Methods

Hematoxylin–eosin and PAX8 immunohistochemical stains were performed on all specimens. In appropriate cases, bleached preparations and other immunohistochemical stains, including AE1/AE3 cytokeratin, Lin28A, and CD45, were performed.

Main Outcome Measures

Distribution of PAX8 expression in normal and neoplastic tissue.

Results

Strong nuclear PAX8 expression was observed in the normal corneal epithelium, iris sphincter pupillae muscle, iris pigment epithelium and dilator muscle complex, nonpigmented and pigmented epithelia of the ciliary body, lens epithelium, and a subset of retinal neurons. The normal retinal pigment epithelium and uveal melanocytes did not stain for PAX8. The ciliary body epithelial and neuroepithelial tumors (adenoma, adenocarcinoma, and medulloepithelioma) showed uniform strong nuclear PAX8 immunoreactivity. All melanocytic tumors (iris melanoma, ciliary–choroidal melanoma, and melanocytoma) and retinal pigment epithelial neoplasms showed negative results for PAX8. A subset of tumor-associated lymphocytes, most prominent in uveal melanoma, showed positive results for PAX8. The uniformity of the PAX8 staining was superior to the variable cytokeratin staining in the ciliary epithelial neoplasms and the variable Lin28A staining in malignant medulloepithelioma. The veracity of PAX8 staining was equally as robust on cytologic analysis and open-flap biopsy specimens of ciliary epithelial and iris epithelial neoplasms, melanocytoma, and melanoma.

Conclusions

PAX8 has proven to be a very useful diagnostic marker in a select group of adult intraocular tumors, and we highly recommend its inclusion in diagnostic antibody panels of morphologically challenging intraocular neoplasms.

Section snippets

Methods

Informed consent was obtained from patients 6, 7, and 8 (Wills Eye Hospital). For patients 1 through 5 and 9 through 34 (Royal Hallamshire Hospital, United Kingdom), ethics committee approval was obtained (study approval nationally; identifier, 15/NW/0239) from the Sheffield Teaching Hospitals Research & Development Office (study no., STH 21118; substudy to study no., STH15427) according to the United Kingdom Human Tissue Act guidelines that permit the use of retrospective, archived human

Results

PAX8 staining was interpreted as positive if it stained the nucleus only. Very little variation was found in the density of the nuclear staining; when positive, it was invariably intensely brown. Some cases showed a blush of nonspecific cytoplasmic staining. Table 1 summarizes the key patient clinical information and the histopathologic details of the tumors.

Discussion

This study mapped the expression of PAX8 protein in normal ocular structures and showed its expression in a select number of intraocular tumors. The expression of PAX8 in iris and ciliary body epithelium, corneal and lens epithelium, and some retinal neurons suggests that PAX8 may be involved in their homeostasis and regeneration.

Observation of PAX8 expression in normal iris pigment epithelium and ciliary body epithelium led to a prediction that tumors arising from these structures may express

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      Citation Excerpt :

      Anti-cytokeratin AE1/AE3 has broad sensitivity for epithelial cells and it can be expressed in tumors such as adenocarcinoma of the nonpigmented ciliary epithelium and renal cell carcinoma.12,13 PAX8 is necessary for the development of the eye, urogenital tract, and thyroid gland; it is commonly expressed in normal tissues as well as in neoplasms originating from these organs.5,6 PAX8 expression has been reported in lesions that retain epithelial morphologic characteristics, such as anterior polar pyramidal cataract and lens epithelial cells entrapped in capsular fibrosis.5

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    See Commentary on page 779.

    Disclosure(s): All authors have completed and submitted the ICMJE disclosures form. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

    Supported by Sheffield Teaching Hospitals Charity Small Grants Fund (grant no.: 340619); and the Pennsylvania Lions Sight Conservation and Eye Research Foundation, Inc., Beaver Falls, Pennsylvania. The funding organizations had no role in the design or conduct of this research.

    HUMAN SUBJECTS: Human subjects were included in this study. The human ethics committees at Wills Eye Hospital and Sheffield Teaching Hospitals Research & Development Office approved the study. All research adhered to the tenets of the Declaration of Helsinki. Informed consent was obtained from patients 6, 7, and 8 (Wills Eye Hospital); for patients 1 through 5 and 9 through 34 (Royal Hallamshire Hospital, United Kingdom), ethics committee approval was obtained (study approval nationally; identifier, 15/NW/0239) from the Sheffield Teaching Hospitals Research & Development Office (study no., STH 21118; substudy to study no., STH15427) according to the United Kingdom Human Tissue Act guidelines that permit the use of retrospective, archived human biopsy material surplus to diagnosis, through block consent from the research office.

    No animal subjects were included in this study.

    Author Contributions:

    Conception and design: Mudhar, Sanderson, Pheasey

    Analysis and interpretation: Mudhar, Milman, Eagle, Sanderson, Pheasey, Paine, Salvi, Rennie, Rundle, C.Shields, J.A.Shields

    Data collection: Mudhar, Milman, Eagle, Sanderson, Pheasey, Paine, Salvi, Rennie, Rundle, C.Shields, J.A.Shields

    Obtained funding: N/A

    Overall responsibility: Mudhar, Milman, Salvi, Rennie, Rundle, C.Shields

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