Expression of PRAME in high-grade serous carcinoma is associated with higher residual disease volume and Occludin expression

Background

Patients with high-grade serous carcinoma (HGSC) are commonly diagnosed at late disease stages and after primary tumors have disseminated in the peritoneum. The overexpression of tight junction proteins has been associated with poor prognosis in this setting, potentially reflecting the tumor´s adaptive changes in the disease cascade.

Methods

By performing immunohistochemistry in a large single-center cohort of a total of 705 HGSC, we test the hypothesis that the protein expression of PReferentially expressed Antigen of MElanoma (PRAME) contains prognostic, predictive or clinically translatable information. We further examine its co-expression with tight junction proteins.

Results

We confirmed the nuclear expression of PRAME in 442 (63 %) of specimens with comparable expression levels in peritoneal and pleural effusions (p = 0.72), and in effusions versus surgical specimens (p = 0.339). In effusions, any degree of expression of PRAME was significantly associated with suboptimal debulking surgery during primary treatment (p = 0.034). In surgical specimens, higher expression of PRAME was significantly linked to more advanced FIGO stage (p = 0.021). PRAME expression was not associated with other clinico-pathologic factors as age, CA125 levels, chemoresistance or survival, but correlated with PRAME mRNA levels. Significant correlation was found between expression levels of PRAME and the tight junction protein Occludin (p = 0.002).

Conclusion

Taken together, our study confirms PRAME to be expressed in the majority of HGSC effusions and surgical samples. The association of high levels of PRAME expression with incomplete surgical resection status and advanced stage disease may suggest PRAME expression as adaptative mechanism during disease dissemination. This finding warrants confirmation in independent series.