Prognostic significance of pigmentation and stem cell markers in Indian population of uveal melanoma.

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.