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Schmoeckel, E; Hofmann, S; Fromberger, D; Rottmann, M; Luthardt, B; Burges, A; Jeschke, U; Kirchner, T; Lax, SF; Mayr, D.
Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma.
Virchows Arch. 2019; 474(5):599-608
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Abstract:
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.
Find related publications in this database (using NLM MeSH Indexing)
Anaplastic Lymphoma Kinase - metabolism
B7-H1 Antigen - metabolism
Biomarkers, Tumor - metabolism
Carcinoma, Endometrioid - diagnosis
Carcinoma, Endometrioid - pathology
Cell Cycle Proteins - metabolism
DNA Mismatch Repair - genetics
Endometrial Neoplasms - pathology
Female -
Humans -
Immunohistochemistry - methods
Microtubule-Associated Proteins - metabolism
Ovarian Neoplasms - diagnosis
Ovarian Neoplasms - pathology
Prognosis -
Receptor, ErbB-2 - metabolism
Serine Endopeptidases - metabolism

Find related publications in this database (Keywords)
Ovarian carcinoma
HER2
ALK
EML4
PD-L1
Mismatch repair deficiency
Microsatellite instability
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