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Eyelid sebaceous gland carcinoma (SGC) is an aggressive skin cancer characterized by a heightened risk of recurrence and metastasis. While surgical excision is the primary treatment, unraveling the molecular intricacies of SGC is imperative for advancing targeted therapeutic interventions and enhancing patient outcomes. This comprehensive review delves into the molecular landscape of eyelid SGC, emphasizing key genetic alterations, signaling pathways, epigenetic modifications, and potential therapeutic targets. Significant findings include aberrations in critical signaling pathways (β-catenin, lymphoid enhancer binding factor, hedgehog, epidermal growth factor receptor, P53, and P21WAF1) associated with SGC progression and poor prognosis. Notably, eyelid SGC manifests a distinctive mutational profile, lacking ultraviolet signature mutations in tumor protein 53 (TP53), indicating alternative mutagenic mechanisms. Next-generation sequencing identifies actionable mutations in genes such as phosphatase and tensin homolog (PTEN) and Erb-B2 receptor tyrosine kinase 2 (ERBB2), facilitating the emergence of personalized medicine approaches. Molecular chaperones, specifically X-linked inhibitor of apoptosis protein (XIAP) and BAG3, emerge as pivotal players in promoting tumor survival and proliferation. The review underscores the role of epithelial-mesenchymal transition, where regulators like E-cadherin, vimentin, and ZEB2 contribute to SGC aggressiveness. Epigenetic modifications, encompassing DNA methylation and microRNA dysregulation, further elucidate the molecular landscape. This review consolidates a comprehensive understanding of the molecular drivers of eyelid SGC, shedding light on potential therapeutic targets and providing a foundation for future investigations in diagnostic, prognostic, and personalized treatment strategies for this formidable malignancy., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Purpose: Eyelid sebaceous carcinoma (SeC) is the third most frequent eyelid malignancy worldwide and is relatively prevalent in Asian patients. An eyelid SeC cell line model is necessary for experimental research to explore the etiology and pathogenesis of eyelid SeC. This study established and characterized an eyelid SeC cell line with a TP53 mutation that might be useful for analyzing potential treatment options for eyelid SeC., Methods: The eyelid SeC cell line SHNPH-SeC was obtained from a patient with eyelid SeC at Shanghai Ninth People's Hospital (SHNPH), Shanghai JiaoTong University School of Medicine. Immunofluorescence staining was employed to detect the origination and proliferation activity. Short tandem repeat (STR) profiling was performed for verification. Chromosome analysis was implemented to investigate chromosome aberrations. Whole exome sequencing (WES) was used to discover genomic mutations. Cell proliferation assays were performed to identify sensitivity to mitomycin-C (MMC) and 5-fluorouracil (5-FU)., Results: SHNPH-SeC cells were successively subcultured for more than 100 passages and demonstrated rapid proliferation and migration. Karyotype analysis revealed abundant chromosome aberrations, and WES revealed SeC-related mutations in TP53, KMT2C, and ERBB2. An in vivo tumor model was successfully established in NOD/SCID mice. Biomarkers of eyelid SeC, including cytokeratin 5 (CK5), epithelial membrane antigen (EMA), adipophilin, p53, and Ki-67, were detected in SHNPH-SeC cells, original tumors, and xenografts. MMC and 5-FU inhibited the proliferation and migration of SHNPH-SeC cells, and SHNPH-SeC cells presented a greater drug response than non-TP53-mutated SeC cells., Conclusions: The newly established eyelid SeC cell line SHNPH-SeC demonstrates mutation in TP53, the most commonly mutated gene in SeC. It presents SeC properties and malignant characteristics that may facilitate the investigation of cellular behaviors and molecular mechanisms of SeC to explore promising therapeutic strategies.

Purpose: To identify the molecular background of eyelid sebaceous gland carcinomas (SCs), we conducted the integrated whole-exome sequencing and transcriptome sequencing for eyelid SCs in this study., Methods: The genetic alterations were studied by whole-exome sequencing, and the messenger RNA expression was studied using Oxford Nanopore Technologies (ONT) in five paired fresh eyelid SC tissues and adjacent normal tissues. Integrated analysis of exome and transcriptomic information was conducted for filtering candidate driver genes. Protein-protein interaction (PPI) network of filtered candidate genes was analyzed by STRING. The protein expression was verified by immunohistochemistry in 29 eyelid SCs and 17 compared normal sebaceous gland tissues., Results: The average numbers of pathogenic somatic single-nucleotide variants (SNVs) and indels in eyelid SCs were 75 and 28, respectively. Tumor protein p53 (TP53), zinc finger protein 750 (ZNF750), filaggrin 2 (FLG2), valosin-containing protein (VCP), and zinc finger protein 717 (ZNF717) were recurrent mutated genes. A mean of 844 differentially expressed genes (DEGs) were upregulated, and 1401 DEGs were downregulated in SC samples. The intersection of DEG-based pathways and mutation-based pathways was mainly involved in microbial infection and inflammation, immunodeficiency, cancer, lipid metabolism, and the other pathways. The intersection of DEGs and mutated genes consisted of 55 genes, of which 15 genes formed a PPI network with 4 clusters. The PPI cluster composed of scavenger receptor class B member 1 (SCARB1), peroxisome proliferator-activated receptor γ (PPARG), peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A) was involved in cholesterol metabolism. The expression of SCARB1 protein was found to be increased, whereas that of PPARG protein was decreased in eyelid SCs compared to that in the normal sebaceous glands., Conclusions: Increased SCARB1 and decreased PPARG indicated that dysregulation of cholesterol metabolism might be involved in carcinogenesis of eyelid SCs., Translational Relevance: The malfunction in cholesterol metabolism might advance our knowledge of the carcinogenesis of eyelid SCs.

Purpose: To investigate the effect on meibomian gland function of super pulse carbon dioxide (CO 2 ) laser excision in the treatment of eyelid tumors at palpebral margin., Methods: 36 patients with 36 eyelid tumor size ≤ 1 cm and within 1 mm to palpebral margin were recruited in this study. Of which, 16 cases with tumors in the upper eyelid and 20 cases in the lower eyelid were involved. The eyelid tumors of all the patients were treated by super pulse CO 2 laser with its power density varied between 0.6 and 21.1 W/mm 2 and in repeat mode. The laser spot size ranged from 120 to 200  μ m. Ocular surface parameters including tear film break-up time (BUT) and meibograde, meibum expressibility, and meibum quality were evaluated at pretherapy, 1 week, 1 month, and 3 months posttherapy in all 36 patients., Result: All the patients were satisfied with the therapy. No infective complications and recurrence occurred in any of the 36 patients at the following period. The eyelid wound recovered well with nearly normal appearing after 2 to 3 weeks. The morphology of limbi palpebralis, BUT, meibograde, meibum expressibility, and meibum quality of all the 36 patients showed no significant difference before and after the therapy., Conclusions: Super pulse CO 2 laser had no effect on meibomian gland function and morphology in the excision of tumors at palpebral margins, which was an efficacy and well-tolerated therapy with lower complications and recurrence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Songjiao Zhao et al.)

Purpose: Eyelid sebaceous gland carcinoma (SGC) is an aggressive but rare malignancy of ocular region. Over-expression of PD-L1 and PD-1 has been demonstrated in a variety of solid tumors including conjunctival melanoma. PD-L1 is an immunoinhibitory molecule that suppresses the effective T cells response against tumor antigen leading to the progression of tumors. Inhibitors of the interaction of PD-L1 and PD-1 are associated with good clinical response various carcinomas. The prognostic value of the PD-1/PD-L1 axis in SGC remains unexplored. The purpose of this study was to evaluate expressions of PD-1 and its ligand PD-L1 in SGC and correlate its expression with clinicopathological features and patients survival., Methods: The immunohistochemical expression of PD-L1 and PD-1 was evaluated in 30 SGC cases., Results: PD-L1 immunopositivity was detected in 41.9% of the SGC cases. PD-1 expression in tumor infiltrative lymphocytes (TILs) was observed in 53.3% samples. Tumor PD-L1 positivity, PD-1 expression in TILs and tumor size (>10 mm) was associated with reduced disease-free survival. On multivariate analysis only tumor size (>10 mm) and a combined positivity of PD-L1 in tumor cells and PD-1 in TILs with an odds ratio of 5.212 (95% confidence interval 1.449-18.737) continued to be significantly associated with SGC recurrence., Conclusion: PD-L1 is overexpressed in 50% of SGC cases. The combined tumor PD-L1 positivity and TILs showing PD-1 expression within the same SGC patient's samples predict high-risk SGC, suggesting that the up-regulation of PD-L1 in tumor cells and PD-1 positivity within the same SGC patient may aggravate tumor recurrence., Competing Interests: None

Competing Interests: There are no conflicts of interest.

Adenoid cystic carcinoma (ACC) is a rarely seen malignant epithelial tumor of the eyelids. We present a rare case of primary ACC arising from the tarsal plate of the lower lid that clinically resembled a chalazion. A 66-year-old female presented with a recurring nodule in her left lower lid. She gave history of surgery for chalazion removal from the same site twice earlier. An initial diagnosis of a recurrent chalazion was made, and incision and curettage was done. Light microscopy showed a solid tumor composed predominantly of sheet-like and nested pattern of basaloid to low-columnar cells with intervening fibrovascular septa and lacking an obvious cribriform or tubular architecture. The tumor cells were positive for pan-cytokeratin and CD117 and negative for adipophilin, HMB45, and BerEP4. A diagnosis of solid variant of ACC of the eyelid was made. Wide excision was performed and eyelid defect was reconstructed., Competing Interests: There are no conflicts of interest

Sweat gland neoplasms are rare adnexal tumors that pose a diagnostic challenge for both, ophthalmologists and pathologists. Endocrine, mucin producing sweat gland carcinoma (EMPSGC), considered to be analogous to the solid papillary mammary carcinoma is one such tumor. It usually affects elderly, is more frequent in women and has a predilection for skin of the eyelid. Although it has an indolent clinical course, EMPSGC is believed to be a precursor of the invasive mucinous carcinoma and has a potential for local recurrence. We report a series of 10 biopsy-proven EMPSGCs with their immunohistochemical features and review the literature., Competing Interests: There are no conflicts of interest

Purpose: A limited number of therapies are available for patients with metastatic eyelid sebaceous carcinoma (SC). Programmed death receptor Ligand 1 (PD-L1) expression and its clinical significance in sebaceous cell carcinoma are presently unknown. This study aimed to evaluate the expression level of PD-L1 in SC., Methods: This single centre, retrospective, and comparative study was conducted at the Ninth People's Hospital between August 1, 2013 and September 1, 2016. Twenty primary, 11 recurrent, and 10 lymph node metastatic eyelid SCs of 41 consecutive patients and paired control eyelid samples were enrolled in the study. Immunohistochemical staining of PD-L1 was performed on slides containing SC embedded in paraffin wax. Patient clinical characteristics and PD-L1 expression related to SC prognostic values were evaluated., Results: Of the 41 patients with eyelid SCs, 58.5% (24/41) were female, and 41.5% (17/41) were male. A total of 43.9% (18/41) were left-sided, and 56.1% (23/41) were right-sided. A total of 2.4% (1/41) of the SCs were located at the canthus, 51.2% (21/41) were located at the upper eyelid, 41.5% (17/41) were located at the lower eyelids, and 2.4% (1/41) invaded the lacrimal sac. A total of 24.4% of the SCs were metastatic (10/41), 48.8% (20/41) were primary tumours, and 26.8% (11/41) resulted from recurrence. A total of 48.8% (20/41) were moderately graded and 51.2% (21/41) were poorly graded. Programmed death receptor Ligand 1 (PD-L1) positive expression was found in 20 (48.8%) cases. Programmed death receptor Ligand 1 (PD-L1) expression was observed on the tumour cell membrane. Higher expression of PD-L1 was correlated with metastatic cases when compared with primary cases (F = 6.69, p = 0.001). There was a higher expression of PD-L1 in the poorly differentiated group compared with the moderately graded group (57.1% poorly graded versus 45.0% moderately graded)., Conclusion and Relevance: Inhibition of PD-L1 expression may be a therapeutic option for metastatic eyelid SCs, although this hypothesis needs to be tested in future clinical trials., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To report the clinical and histopathologic features of two cases of eyelids metastases from uveal melanoma diagnosed in a metachronous and synchronous fashion., Methods: Monocentric retrospective case series of histopathologically proven eyelids metastases from uveal melanoma at our institution., Results: Two patients were presented to our hospital for upper eyelids pigmented and firm lesions. Patient 1 had an history of left uveal melanoma treated conservatively with proton beam therapy 5 years earlier. Examination revealed bilateral upper eyelids lesions. Patient 2 had no malignancy history but was incidentally diagnosed with a cerebral nodule few months earlier. Examination revealed a right upper eyelid nodule and a previously unknown right uveal melanoma. Excisional biopsy was performed for both patients. Pathological assessment allowed the presence of melanoma cells. The lack of BAP1 nuclear expression on immunohistochemistry as well as the absence of cutaneous or mucosal melanoma were consistent with an uveal origin. Diffuse metastatic spread was noted for both patients. Systemic therapies were prescribed. Patient 1 died from metastatic spread (62 months and 4 months after uveal melanoma diagnosis and eyelids metastases removal, respectively) whereas patient 2 was still alive (14 months follow up)., Conclusions: Eyelids metastases from uveal melanoma is an exceptional finding. Excisional biopsy and pathological assessment are of main importance to confirm the diagnosis and to identify genetic mutations for further targeted therapies. Currently, prognosis remains poor.

Primary mucinous adenocarcinoma (PMA) of the eyelid is an exceptionally rare clinical entity. Often, it mimics with benign lesions on clinical examination and with metastatic mucinous adenocarcinoma on histological examinations. We report a case of PMA in a 60-year- old male patient who came with a slow-growing, painless swelling near the lower lid of the left eye. Excisional biopsy from the mass revealed a mucinous adenocarcinoma. To differentiate it from a metastatic mucinous adenocarcinoma, a wide range of immunohistochemistry panel was run. The tumor cells showed strong positivity for cytokeratin7, cytokeratin5/6, P63, estrogen receptor, progesterone receptor and negativity for cytokeratin20. Moreover, extensive metastatic work-up did not show any primary malignancy elsewhere, hence a final diagnosis of PMA was made. We believe that, this is the second reported case from the Middle East and the first in the Madinah region of Saudi Arabia.

Background: Bcl-2-associated athanogene 3 (BAG3), a co-chaperone of heat shock protein 70 (HSP70), has been shown to play a role in anti-apoptosis of various malignant tumors. In this study, the expression of BAG3 was examined in human sebaceous gland carcinoma of the eyelid., Materials and Methods: The expression of BAG3 was evaluated by immunohistochemistry of surgical samples from 5 patients with sebaceous gland carcinoma in the eyelid., Results: BAG3 was positive diffusely in the cytoplasm in all patients. The average positive rate of BAG3 was 73.0±26.0% in tumor cells of all patients., Conclusion: BAG3 was highly expressed in sebaceous gland carcinoma of the eyelid. BAG3 may play an important role in the pathogenesis and progression of sebaceous gland carcinoma of the eyelid., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Eyelid sebaceous carcinoma (SC) remains a common diagnostic pitfall for both the clinician and histopathologist. The aim of this study was to describe perforin as a new marker in the immunohistochemistry panel for SC., Methods: A total of 29 cases were retrieved from the Pathology archives, including 11 sebaceous neoplasms (nine SC; two sebaceomas), 10 squamous cell carcinomas (SCC) and eight basal cell carcinomas (BCC). These were stained using the monoclonal antibody for perforin, epithelial membrane antigen (EMA), Ber-EP4 and adipophilin (ADP). Sensitivity and specificity of perforin as an immunohistologic marker for sebaceous tumours were compared to EMA, ADP and Ber-EP4., Results: Perforin stained strongly 9/11 (81%) of the sebaceous neoplasms (SN), 7/9 SC and 2/2 of sebaceomas (2/2), similar to ADP. Epithelial membrane antigen (EMA) stained 8/9 SC and was negative (1/2) or only very weakly expressed (1/2) in sebaceomas. The specificity of perforin in identifying SN versus SCC and BCC was 100% (95% CI 69-100), while EMA specificity in identifying SN varied according the comparison group (SCC: 50%, 95% CI 18-81, 100% (95% CI 63-100). Perforin better highlighted the intraepithelial spread of SC than EMA. Ber-EP4 was strongly expressed in six of nine SC, but was consistently negative in sebaceomas., Conclusions: The expression pattern of perforin in sebaceous neoplasms enables us to recommend the use of perforin as a new immunohistochemical marker for sebaceous neoplasms., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

A tumor represents an abnormal tissue growth that can arise from any ocular structure, such as eyelids, muscles or the optic nerve. At the eyelids, there are two main tumor types: basal cell carcinoma and squamous cell carcinoma. Angiogenesis plays a crucial role in growth, invasion and metastasis processes of any tumor. It is well known the fact that without new vessels formation tumors cannot exceed 1-2 mm diameter. Immunohistochemical analysis has been performed on 43 cases of primary carcinomas of the eyelid, diagnosed between 2010 and 2014 in the Laboratory of Pathological Anatomy of the University Emergency County Hospital of Craiova, Romania. Biological material was represented by surgical resection samples, coming from the Clinic of Ophthalmology the anteriorly named Hospital. Within the immunohistochemical study, we have evaluated epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) expression in a group of 43 cutaneous carcinomas of the eyelid, depending on the type and differentiation grade of the tumor. Of the 43 samples, 23 came from patients with eyelid basal cell carcinoma and 20 came from patients with eyelid squamous cell carcinoma. In our study, EGFR and VEGF immunoexpression was superior for squamous cell carcinomas, compared to basal cell carcinomas, fact that was statistically significant. Regarding squamous cell carcinomas, the immunoexpression of these two markers was superior in moderate÷poor differentiated forms, compared to well differentiated forms, fact that was statistically significant. The markers used in this study were found to be associated with the acquisition of aggression and angiogenic phenotypes by analyzed carcinomas.

Background: Sebaceous cell carcinoma of the eyelid is a malignant tumor. However, the pathoetiology of sebaceous cell carcinoma is not clear. Retinoic acid (RA) signaling is essential for skin epidermal differentiation including the eyelids. In this study, we investigate the expression of β-catenin, RA-binding proteins and RA receptors in sebaceous cell carcinoma of the eyelid and try to estimate their influence on its pathoetiology., Methods: Retrospective, noncomparative, consecutive interventional case series. Sixteen cases of eyelid sebaceous gland carcinoma who received tumor excision at our hospital between 2001 and 2011 were included. Immunohistochemical staining for β-catenin, cellular retinoic acid binding protein 1 (CRABP1), cellular retinoic acid binding protein 2 (CRABP2), fatty acid-binding protein 5 (FABP5), retinoic acid receptors (RAR-α, -β, -γ), and retinoid X receptors (RXR-α, -β, -γ) was performed on tissue samples obtained from tumor excision., Results: Of the 16 sebaceous cell carcinoma cases reviewed, six were male and 10 female. The mean follow-up period was 6.7 ± 3.66 years (range, 0.3-13 years). Of these 16 cases, the expression of β-catenin was significantly increased in sebaceous cell carcinoma cases. CRABP1 was similarly expressed in the sebaceous cell carcinoma and control groups. CRABP2 and FABP5 were expressed in hair follicles of lid skin in both groups, whereas the CRABP2 and FABP5 were aberrantly expressed in the tumor cells of the sebaceous glands. Notably, the expression of retinoic acid receptor (RAR-β) and retinoid X receptors (RXR-β, -γ) was significantly upregulated in sebaceous cell carcinoma of the eyelids., Conclusions: Our findings indicate that retinoic acid signaling is related to the pathogenesis of sebaceous cell carcinoma of the eyelids.

Purpose: To investigate the expression of cancer stem cell (CSC) marker proteins in eyelid sebaceous gland carcinoma and evaluate the clinical significance., Methods: Archival tissue blocks from 50 cases of eyelid sebaceous gland carcinoma were tested via immunohistochemistry for 16 putative CSC markers. Levels of protein expression were analyzed alongside various clinicopathologic parameters such as metastasis-free survival time., Results: Ten patients (20%) showed nodal or distant metastasis during the follow-up period (median, 35.2 months; range, 1-128 months) without any mortality in our series. Among the 16 markers, ALDH1, CD44, CD133, ABCG2, Sox4, Sox9, and slug were selected for candidates of CSC markers because they were frequently and predominantly found in the tumor cells compared with control tarsus cells, which showed negative or very low expression. Univariate analysis revealed that ALDH1, CD133, and ABCG2 were significantly associated with metastasis; patients with ALDH1- or CD133-positive tumors developed metastasis more frequently than patients with tumors that were negative for these markers (log-rank test, P = 0.014, P = 0.013, respectively), and diffuse expression of ABCG2 was associated with significantly shorter metastasis-free survival (log-rank test, P = 0.010). Multivariate Cox proportional hazard model revealed that ALDH1 (hazard ratio [HR] = 5.682, P = 0.038) was significantly associated with metastasis., Conclusions: Development of metastasis in eyelid sebaceous gland carcinoma might be attributed to increased number of CSCs or acquisition of dedifferentiated phenotype. Our findings suggest that CSCs are involved in the disease progression of eyelid sebaceous gland carcinoma, and in particular, expression of ALDH1 is a predictor of a poor outcome., (Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose: The study aimed at evaluating the expression of androgen receptor (AR) and nuclear survivin (NS) in periocular sebaceous gland carcinoma (SGC) and to determine whether this expression is associated with histopathological features, markers of apoptosis and proliferation and with clinical outcomes., Methods: This was a retrospective, comparative case series which included 56 patients with a biopsy-proven periocular SGC. Immunohistochemical staining for AR, survivin, p53 and Ki-67 was analysed in all cases., Results: All patients expressed AR, p53 and Ki-67 in the nucleus of tumour cells. Twenty-four patients (42.8%) had a high AR score, and 32 patients (57.2%) had a low AR score. Twenty-four (42.8%) patients expressed survivin in the nucleus of tumour cells. Nine (37.5%) had a high NS score, and 15 (62.5%) had a low NS score. Patients with a high AR score had a greater recurrence (p < 0.005), higher expression of Ki-67 (p < 0.0001) and a lower p53 expression (p < 0.005). Nuclear expression of survivin correlated with a high Ki-67 labelling index (0.0001) and low p53 expression (<0.005). Neither nuclear expression of survivin nor the NS score correlated with any clinicopathological features., Conclusion: Expression of AR significantly impacts prognosis and is thus promising prognostic marker in periocular SGC., (© 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: The purpose of this study was to detect mutation of the p53 gene, to assess its relationship with p53 or p21(WAF1/CIP1) expression, and to evaluate the correlation between p53 mutation or p21(WAF1/CIP1) expression and clinicopathologic findings in sebaceous carcinoma of the eyelid., Methods: Fifteen conventional paraffin-embedded samples of sebaceous carcinoma of the eyelid were analyzed. Using the single-strand conformation polymorphism technique, the authors sequenced coding exons 5-8 of the p53 gene. The expression of p53 and p21(WAF1/CIP1) protein was analyzed by immunohistochemistry., Results: In 10 of the 15 cases (66.7%), point mutations were detected in the p53 gene. CC to TT double-base changes (tandem mutations), which are known to be induced only by UV, were not detected in any of the mutations. Correlations between p53 mutation and expression were found to be statistically significant (P = 0.007). There was no significant correlation between p53 mutation and clinicopathologic findings or p21(WAF1/CIP1) expression. However, there was a significant inverse correlation between p21(WAF1/CIP1) expression and presence of lymph node metastasis (P = 0.007)., Conclusions: Among human cancers, sebaceous carcinoma of the eyelid may be one of those showing most frequent mutation of the p53 gene, which may not be caused by exposure to UV. p21(WAF1/CIP1) downregulation may be associated with lymph node metastasis.

Purpose: Crystallins are molecular chaperones that protect various cells from apoptosis. This study used immunohistochemistry to examine the expression of alphaA-crystallin and alphaB-crystallin in human sebaceous carcinoma tissues., Methods: Nine patients with sebaceous carcinoma of the eyelid underwent excision of the eyelid or orbital exenteration. Formalin-fixed, paraffin-embedded tissue sections were submitted for hematoxylin-eosin staining and immunohistochemistry with anti-alphaA- and alphaB-crystallin antibodies., Results: In the noncancerous eyelid, crystallins were weakly and homogeneously expressed in the Meibomian gland lobules. In eyelids with sebaceous carcinoma, alphaA-crystallin and alphaB-crystallin were highly expressed in 4 cases, where the cytoplasmic immunoreactivity was heterogeneously detected in the tumor cells. Three and 2 cases were shown to express low levels of alphaA-crystallin and alphaB-crystallin, respectively. A statistically significant correlation was observed between expression levels of alphaA-crystallin and alphaB-crystallin in sebaceous carcinomas (p=0.012). All sebaceous carcinoma tissues contained mitotic tumor cells, which showed predominantly perinuclear immunoreactivity of alphaB-crystallin. The mitotic rate of tumor cells was 5.85+/-1.76 and 10.72+/-1.64 in high and moderate/low alphaB-crystallin-expressing cases, respectively. The number of mitotic cells was significantly higher in moderate/low alphaB-crystallin-positive than in high-positive cases (p<0.01)., Conclusions: Crystallins are expressed in human sebaceous carcinomas including mitotic cells. Expression of alphaB-crystallin correlated with low number of mitotic tumor cells, suggesting that alphaB-crystallin may play a potential role in the regulation of tumor cell proliferation.

Schwannoma, also referred to as neurilemmoma, is a benign tumor of peripheral nerve arising from Schwann cells that form the neural sheath. Schwannoma of ophthalmic interest is rare although it has been reported in relation with the orbit, and less frequently with the uveal tract and conjunctiva. Isolated eyelid schwannoma is extremely uncommon. Up until now, only eight cases have been reported in literature. Herein, we report two cases of eyelid schwannoma.

Meibomian cell carcinoma (MCC) is a malignant tumor of the meibomian glands located in the eyelids. No information exists on the cytogenetic and genetic aspects of MCC. There is no report on the gene expression profile of MCC. Thus there is a need, for both scientific and clinical reasons, to identify genes and pathways that are involved in the development and progression of MCC. We analyzed the gene expression profile of MCC by the microarray technique. Forty-four genes were upregulated and 149 genes were downregulated in MCC. Differential expression data were confirmed for 5 genes by semiquantitative RT-PCR in MCC tumors: GTF2H4, RBM12, UBE2D3, DDX17, and LZTS1. We found dysregulation of two major pathways in MCC: MAPK and JAK/STAT. Clusters of genes on chromosomes 1, 12, and 19 were dysregulated in MCC. The data presented here will facilitate the identification of specific markers and therapeutic targets for the treatment of MCC patients.

Background: Merkel cell carcinoma (MCC) of the eyelid is a rare malignant solid tumor of the elderly, which demonstrates a large, firm, reddish nodule mimicking an angiomatous lesion. The expression of erythropoietin (Epo) and Epo receptor (EpoR), as well as vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR) and basic fibroblast growth factor (bFGF) were examined in human MCC tissues., Materials and Methods: Three patients diagnosed with MCC of the eyelid underwent surgical excision. Isolated tissues were fixed by 4% paraformaldehyde and then were examined using immunohistochemistry., Results: The carcinoma cells consisted of irregular tumor nests with linear stroma and showed hypercellularity indicated by small round nuclei with several mitoses. While immunoreactivity of Epo was undetectable, an increased expression of EpoR was noted in the carcinoma cells. Cytoplasmic immunoreactivity for EpoR was detected in a variety of carcinoma cells, including mitotic cells. VEGF, VEGFR, and bFGF, other angiogenic factors were not expressed in the MCC tissues., Conclusion: EpoR was highly expressed in MCC of the eyelid, suggesting that the Epo-EpoR pathway plays an important role in the formation of MCC.

Human papilloma virus (HPV) infection and loss of P53 function have been identified as frequent events in various human tumors. The aim of this study was to evaluate P53 protein expression and to detect HPV in the tissue samples of 45 benign (papillomas) and 38 malignant conjunctival and eyelid lesions (27 basal cell carcinomas and 11 squamous cell carcinomas). We also looked for eventual relationships between P53 expression and clinicopathological features such as age, histological type of tumor, grading and staging. HPV infection was detected using the PCR-RFLP method. Specific primers were engaged and PCR products of HPV 16, 18, and 33, underwent enzymatic digestion at 37 degrees C. We revealed P53 protein expression in 30 out of 45 (66.6%) squamous cell papillomas. In the SCC and BCC groups, P53 was present in 31 out of 38 carcinomas and there was a statistically significant correlation between histological type of tumor and P53 protein expression. Malignant type HPV 16 and 18 were detected in three squamous cell papillomas, two BCCs and one SCC. However, we observed P53 protein expression in only two HPV-positive papillomas and one infiltrative type of BCC. P53 is probably involved in the development of conjunctival and eyelid tumors due to its high rate of presence in both benign and malignant neoplasms of these organs. HPV seems to occur rarely. In some cases its role in the pathogenesis of conjunctival and eyelid tumorigenesis should be considered as auxiliary.

The aim of this work was to analyse the distribution pattern of S-100-immunoreactive elements in the upper eyelid of the sheep. This pattern may be of importance regarding the diagnosis and prognosis of eyelid tumours that are linked to deregulation of S-100 gene expression. Thirty upper eyelids taken from 15 adult male Ovis aries were studied by means of the peroxidase-antiperoxidase method for light microscopy. S-100-immunopositive cells were found in the eyelid edge. S-100-immunopositive steams and thinner fibres were found throughout the eyelid. These nerve processes typically were denser around glands, hair follicles and blood vessels. S-100-immunopositive elements may play a role as neuromodulator and also in the development of the vegetative innervation of the epithelium and its derivatives.

The aim of our study was an evaluation of the expression of cell proliferation markers (PCNA and Ki-67) in conjunctival and eyelid papillomas and squamous and basal cell cancers. A series of 9 cases of squamous cell cancer (SCC), 15 cases of basal cell cancer (BCC) and 43 cases of squamous cell papilloma (SCP) were assessed using the immunohistochemical method with monoclonal antibodies. PCNA overexpression was observed in 100% of SCP, in 88.8% of SCC and in 100% of BCC cases. Ki-67 overexpression was seen in 32.5% of cases of SCP, in 22.2% of SCC and in 66.6% of BCC. The results showed that an evaluation of Ki-67 expression is the most valuable cell proliferation marker.

Ocular sebaceous carcinoma (OSC) is an uncommon malignancy with a potential to recur and metastasize. Some characteristics of sebaceous carcinoma, such as female preponderance, shown in the present series during 11-year period at Korea Cancer Center Hospital, led us to study their hormone receptors and c-erbB-2 expression. c-erbB-2 overexpression was very common (83%) in OSC, and was not associated with pathologic findings or clinical outcome. Interestingly, estrogen and progesterone receptor was detected in 4 and 2 cases, respectively, suggesting a role of hormonal influence on this neoplasm. Immunohistochemical and clinicopathologic features of 18 cases of OSC in Korea are presented.

Purpose: To determine the effect of adenovirus-mediated gene transfer of a soluble receptor of vascular endothelial growth factor (VEGF) on the growth of experimental eyelid malignant melanoma., Methods: An adenovirus vector encoding a soluble VEGF receptor/flt-1 (Adflt-ExR) was constructed. The bovine retinal endothelial cells (ECs) were incubated in a culture medium of 293E1 cells infected by means of an adenovirus vector or uninfected (control), which contained human recombinant VEGF, and the [3H]thymidine uptake was tested. The experimental eyelid malignant melanoma was induced by the injection of B16 melanoma cells (4 x 10(6) cells) into the right upper eyelid of BALB/c nu/nu mice, and the size of the tumor was recorded for 3 weeks after tumor cell injection. The effect of Adflt-ExR was examined in three ways. Model 1: B16 cells were infected by Adflt-ExR beforehand (at a multiplicity of infection [MOI] of 10) and injected into the eyelid. Model 2: Adflt-ExR was injected into pre-established B16 cell-induced eyelid malignant melanoma. Model 3: Adflt-ExR was injected into the femoral muscle of mice before B16 cell injection into the eyelid, and the remote effect was evaluated. An adenovirus vector bearing the LacZ gene (AdLacZ) or phosphate-buffered saline was used as a control. The amount of VEGF and the flt-ExR protein was measured by sandwich enzyme-linked immunosorbent assay (ELISA). Vascularization was evaluated by counting the number and the size of the vessels., Results: The supernatant of Adflt-ExR-transfected cells clearly inhibited VEGF-induced bovine retinal EC proliferation in vitro. In models 1 and 2, the tumor growth in Adflt-ExR-treated mice was significantly lower than that of controls (P < 0.05). In model 3, no significant difference was found (P = 0.14). The molar ratio of VEGF/flt-ExR protein was clearly low in the tumors of Adflt-ExR-treated mice in models 1 and 2 (P < 0.01) but not in model 3 (P > 0.05). In vessel density, the tumors in Adflt-ExR-treated mice had fewer vessels than tumors in control animals in models 1 and 2 (P < 0.05)., Conclusions: Adenovirus-mediated gene transfer of a soluble form of VEGF receptor (flt-1) gene inhibited the growth of the experimental eyelid malignant melanoma. This method may be useful as an antiangiogenic therapy for eyelid malignant melanoma.