Functional estrogen receptor signaling pathway activity in high-grade serous ovarian carcinoma as compared to estrogen receptor protein expression by immunohistochemistry
| Autor: | Jurgen M.J. Piek, Phyllis van der Ploeg, Laura A.M. van Lieshout, Marjolein H.F.M. Lentjes-Beer, Ruud L.M. Bekkers, Steven L. Bosch, Anja van de Stolpe |
|---|---|
| Přispěvatelé: | Obstetrie & Gynaecologie, RS: GROW - R2 - Basic and Translational Cancer Biology |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adult Cancer Research Short Communication High-grade serous ovarian carcinoma Estrogen receptor Biology 03 medical and health sciences 0302 clinical medicine Estrogen receptor signaling pathway Ovarian carcinoma Biomarkers Tumor Humans RNA Messenger Gene Aged Retrospective Studies Aged 80 and over Ovarian Neoplasms Messenger RNA Reverse Transcriptase Polymerase Chain Reaction Estrogen Receptor alpha General Medicine Middle Aged Immunohistochemistry Cystadenocarcinoma Serous Serous fluid 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Molecular Medicine Female Signal transduction Neoplasm Grading Signal Transduction Signaling pathway activity |
| Zdroj: | Cellular Oncology (Dordrecht) Cellular oncology, 44(4), 951-957. Springer |
| ISSN: | 2211-3428 |
| DOI: | 10.1007/s13402-021-00600-5 |
| Popis: | Purpose Anti-estrogen therapy may be used as a palliative treatment option in high-grade serous ovarian carcinomas (HGSC). However, clinical implementation is limited as the use of estrogen receptor (ER) protein expression by immunohistochemistry remains insufficient in predicting therapy response. To determine the accuracy of ER protein expression as a marker for ER signaling pathway activity, we aimed to correlate ER protein expression to functional ER signaling pathway activity in HGSC. Methods Immunohistochemical ER protein expression was visually scored using total percentages of stained tumor cells and histoscores. Subsequently, mRNA was extracted, and RT-qPCR analysis was performed. Functional ER pathway activity was assessed by a computational Bayesian model inferring ER signaling pathway activity from mRNA levels of ER-specific target genes. Results Our analysis of 29 HGSCs shows that neither total percentage of ER protein expression, nor ER histoscores are significantly correlated to ER signaling pathway activity (respectively, p = 0.473 and p = 0.606). Classification of HGSC into three groups based on ER histoscores 0–100 (n = 6), 101–200 (n = 15) and 201–300 (n = 8) resulted in comparable mean ER signaling pathway activity among the groups (p = 0.356). Several samples in the higher ER histoscore groups had low ER signaling pathway activity, indicating that nuclear ER protein expression is not sufficient to describe transcriptional ER activation. Conclusion Positive immunohistochemical ER staining is not always indicative of an active ER signaling pathway and is, therefore, a poor predictor of anti-estrogen response. Further research is needed to prove the predictive value of ER signaling pathway activity regarding anti-estrogen sensitivity in HGSC patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink