Cornulin as a Potential Novel Biomarker for Cutaneous Squamous Cell Carcinoma.

Background This study aimed to evaluate the expression of an epidermal differentiation marker, cornulin, in cutaneous squamous cell carcinoma (cSCC). Cornulin has been found to be downregulated in various squamous cell carcinomas of other tissues; however, its expression in cSCC has never been studied. We predicted that cornulin expression in cSCC is reduced compared to the normal epidermis. Moreover, we hypothesized that an inverse relationship exists between cornulin expression and the loss of differentiation, as defined by histopathological grading of cSCC lesions. Methodology Samples of normal skin and cSCC lesions of variable histopathological grades were stained using immunohistochemistry. High-resolution tissue images were analyzed with Aperio ImageScope (Leica Biosystems) utilizing a positive-pixel-counting algorithm to quantify the staining intensity. Histo-score (H-score) was calculated based on staining intensity and percentage of positive cell staining. Mean H-scores were compared using an unpaired t-test. Results We documented cornulin expression in cSCC for the first time. Cornulin levels were downregulated by more than two-fold in cSCC compared to the normal epidermis. Additionally, we observed a 4.5-fold downregulation in cornulin expression in tumors with high histopathological grades when compared to low histopathological grade tumors. Conclusions Cornulin expression levels measured through immunohistochemistry staining can help distinguish among the different histopathological grades of cSCC. Therefore, we propose that cornulin detection can be an adjunct to pathological examination to evaluate the differentiation status of cSCC specimens. Longitudinal studies are needed to establish the utility of cornulin as a diagnostic and prognostic biomarker for cSCC.

Cornulin as a Prognosticator for Lymph Node Involvement in Cutaneous Squamous Cell Carcinoma.

Background Cornulin is an epidermal differentiation marker and a stress-related protein. Its expression patterns are likely to reflect the multi-step tumorigenesis process of cSCC, given its role as a tumor suppressor. The aim of this study is to evaluate the utility of Cornulin as a prognosticator for cutaneous squamous cell carcinoma (cSCC). Specifically, the correlation between Cornulin expression and the clinicopathological parameter of lymph node involvement (nodal status), which plays a major role in determining cSCC prognosis and recurrence. We predicted that Cornulin expression declines as cSCC tumors metastasize to regional lymph nodes. Methodology Tissue samples of cSCC lesions of variable nodal involvement status were stained using immunohistochemistry, and high-resolution images were acquired. Aperio ImageScope software (Leica Biosystems) equipped with a positive-pixel-counting algorithm was used to quantify the staining intensity. Subsequently, Cornulin immunoreactivity was calculated as a Histo-score (H-score) value, which is based on the staining intensity and the percentage of positively stained cells. Mean H-scores were compared between groups using an unpaired t-test. Results A significant inverse correlation was found between Cornulin expression levels and metastasis to the lymph nodes. Specifically, primary tumors with metastasis to regional lymph nodes (N1) exhibited 9.5-fold decrease in Cornulin immunoreactivity compared to the primary tumor samples without lymph node involvement (N0). Conclusion Cornulin was found to be significantly downregulated in primary tumors with lymph node metastases. Detection assays to measure Cornulin expression in cSCC primary tumors might aid in determining the nodal status in these patients and possibly help determine cases of occult lymph node metastasis or micrometastasis. Future clinical studies are needed to help establish Cornulin's role in enhancing the predictive power of histopathological examination and improving survival rates for patients suffering from this type of skin cancer.