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Diagnostic utility of immunohistochemistry in concordance with mRNA analysis of PRAME in the stratification of high-risk uveal melanoma patients

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Abstract

Existing clinical indicators for metastatic risk classification and patient treatment of uveal melanoma (UM) in the Asian population are limited. Preferentially expressed antigen in melanoma (PRAME) has gained attention in the prognosis of cancers and considered as a potential biomarker in many tumors including UM. Therefore, this study investigated the expression of PRAME and its association with loss of nuclear BAP1 (nBAP1) as well as its correlation with clinicopathological parameters and patient outcome. Immunohistochemical expression of PRAME and BAP1 proteins were assessed in 66 prospective cases of UM. mRNA expression level was measured by quantitative real-time PCR. Kaplan–Meier curves and Cox proportional hazard models were used to analyze the correlation of protein expression with clinicopathological parameters, metastasis-free survival and overall survival. Nuclear PRAME (nPRAME) expression and loss of nBAP1 were observed in 24 and 62% cases, respectively. PRAME mRNA expression level was found to be upregulated in 64% (7/11) of metastatic patients. mRNA and immunoexpression of nPRAME were statistically significant with many clinicopathological high-risk factors. On univariate and multivariate analyses, high mitotic activity, extraocular invasion and presence of nPRAME expression were statistically significant (p < 0.05). On Kaplan–Meier survival analysis, patients expressing PRAME had significantly reduced metastasis-free survival (MFS) and overall survival (OS). MFS and OS were also reduced in patients expressing PRAME along with loss of nBAP1. Our data show that nPRAME expression, in combination with loss of nBAP1, could be a useful predictive biomarker in the therapeutic management of UM patients at high risk.

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Acknowledgements

Nikhil Kumar is thankful to the Indian Council of Medical Research for providing Junior Research Fellowship.

Funding

This research was funded by Indian Council of Medical Research (F. No. 5/4/6/3/OPH/2019-NCD-II).

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Contributions

MKS and SK were responsible for the conception and design of the work. NK, LS and MKS contributed to the acquisition, analysis, and interpretation of data for the work. NL and RM provided the enucleated specimens. SS and SK helped in reviewing the histopathology slides. All the authors reviewed and approved the final version of the manuscript.

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Correspondence to Lata Singh or Seema Kashyap.

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Ethical approval was obtained from the Institute’s Ethical Committee, All India Institute of Medical Sciences (Ref. No. IEC-189/05–04-2019).

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Written informed consent was obtained from all the patients before participation in this study.

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Kumar, N., Singh, M.K., Singh, L. et al. Diagnostic utility of immunohistochemistry in concordance with mRNA analysis of PRAME in the stratification of high-risk uveal melanoma patients. Human Cell 36, 342–352 (2023). https://doi.org/10.1007/s13577-022-00808-z

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