Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma
Most ovarian carcinomas (OC) are characterized by poor prognosis, particularly the most frequent type high-grade serous carcinoma. Besides PARP inhibitors, target-based therapeutic strategies are not well established. We asked the question which other therapeutic targets could be of potential value and, therefore, analyzed a large cohort of OC for several predictive factors. Two hundred eighty-eight (288) cases of OC including the major histological types were analyzed by immunohistochemistry for PD-L1HER2, ALK, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. HER2 amplification and ALK/EML4 fusion were assessed by fluorescence in situ hybridization. The most frequent finding was PD-L1 expression ≥ 1% in 19.5% of the cases, which correlated with a significantly better overall survival in multivariate analysis (p < 0.001). HER2 amplification was detected in 11 cases (4%), all high-grade serous carcinomas. Amplification of HER2 did not correlate with patients’ survival. ALK/EML4 fusion was found in two cases (0.74%): one high-grade serous and one endometrioid carcinoma. MMR deficiency was only present in one case of stage IV high-grade serous carcinoma. Subsets of high-grade serous carcinomas show PD-L1 expression and HER2 amplification, respectively, and, therefore, could qualify for immune checkpoint inhibitor therapy or anti HER2 therapy. PD-L1 is also of prognostic impact. ALK/EML4 fusion is very rare in OC and not a putative therapeutic target.
KeywordsOvarian carcinoma HER2 ALK/EML4 PD-L1 Mismatch repair deficiency Microsatellite instability
Doris Mayr designed the study. Elisa Schmoeckel designed the study and wrote the first draft of the manuscript. Elisa Schmoeckel, Sophie Hofmann, Daniel Fromberger, and Beate Luthardt carried out the research work and analyzed the data. Miriam Rottmann supported the statistical analyses. Doris Mayr, Alexander Burges, Udo Jeschke, Miriam Rottmann, Thomas Kirchner, and Sigurd F. Lax reviewed and edited the manuscript. All authors gave final approval for publication.
Elisa Schmoeckel takes full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.
Compliance with ethical standards
All patients’ data were fully anonymized, and the study was performed according to the standards set in the Declaration of Helsinki 1975. The current study was approved in writing by the Ethics Committee of the Ludwig-Maximilians-University, Munich, Germany (approval number 18-130).
Conflict of interest
There are no business relationships that might lead to a conflict of interest.
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