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Oncology
Laboratory science
Prognostic significance of pigmentation and stem cell markers in Indian population of uveal melanoma
  1. Nikhil Kumar1,
  2. Mithalesh Kumar Singh2,
  3. Lata Singh3,
  4. Jayanti Jha1,1,
  5. Neelam Pushker4,
  6. Neiwete Lomi4,
  7. Rachna Meel4,
  8. Seema Sen1,
  9. Seema Kashyap1
  1. 1 Ocular Pathology, All India Institute of Medical Sciences, New Delhi, India
  2. 2 Dermatology, University of California, Irvine, California, USA
  3. 3 Pediatrics, All India Institute of Medical Sciences, New Delhi, India
  4. 4 Ophthalmology, All India Institute of Medical Sciences, New Delhi, India
  1. Correspondence to Professor Seema Kashyap; seemakashyap65{at}gmail.com; Dr Mithalesh Kumar Singh; mithalesh.aiims{at}gmail.com

Abstract

Background Increased pigmentation has been associated with cancer stem-cell-like behaviour and chemoresistance in uveal melanoma (UM) and cutaneous melanoma. Therefore, our present study determines the correlation between pigmentation and cancer stem cell markers in UM patients.

Methods Expression of PAX3, CD133, ABCG2, TRYP1, TRYP2 and microphthalmia-associated transcription factor (MITF) was assessed by immunohistochemistry along with mRNA expression level of PAX3 using quantitative real-time PCR in 70 prospective UM cases. Kaplan-Meier analysis and Cox-proportional hazards model were used to analyse the correlation of protein expression with clinicopathological parameters and patient outcome.

Results We found significant expression of PAX3, CD133 and ABCG2 proteins in 28/70 (40%), 34/70 (49%) and 31/70 (44%) cases, respectively. There was a positive correlation between nuclear expression of PAX3 and high-risk clinicopathological parameters such as necrosis and scleral invasion (p<0.01). CD133 and ABCG2 expression were positively correlated with distant metastasis (p=0.03 and 0.01). Immunoexpression of PAX3, CD133 and ABCG2 proteins was positively correlated with MITF. TYRP2 expression correlated with PAX3 and ABCG2 immunoexpression. Tumour pigmentation was not correlated with any of the markers. PAX3 mRNA expression was positively correlated with immunoexpression of CD133 (p<0.01), ABCG2 (p=0.01) and distant metastasis (p<0.01). On Kaplan-Meier survival analysis, reduced metastasis-free survival was observed in patients with tumours showing high CD133 and ABCG2 expression. No significant correlation was observed between tumour pigmentation and overall survival.

Conclusion Our study highlights the association between PAX3 expression, pigmentation markers such as MITF and TRYP2 and cancer stem-cell markers in UM progression.

  • Choroid
  • Pathology
  • Prognosis

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable.

https://doi.org/10.1136/bjo-2024-325886

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable.

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    Footnotes

    • MKS and SK contributed equally.

    • NK and LS contributed equally.

    • Correction notice This paper has been corrected since it was first published. Figure 4 has been replaced with the right version.

    • Contributors NK executed the study and data analysis in association with LS and MKS. JJ helped with data analysis. LS and MKS contributed to the design and draft of the manuscript. NL, NP and RM provided the enucleated specimens and follow-up of the patients. SS and SK were responsible for histopathological examination. SK responsible for the overall content as guarantor. The guarantor accepted full responsibility for the work and/or the conduct of the study, had access to the data and controlled the decision to publish. All authors reviewed and agreed to the published version of the manuscript.

    • Funding This research was funded by Indian Council of Medical Research, New Delhi (File no. 5/4/6/3/OPH/2019-NCD-II).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.