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Expression of palladin is associated with disease progression in metastatic high-grade serous carcinoma
Ben Davidson1,2, Annika Jøntvedt Bock1, Arild Holth1
1Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.
Objective:
To analyse the expression and clinical role of the actin-associated molecule palladin in serous effusions.
Methods:
PALLD mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction in 83 high-grade serous carcinoma (HGSC) effusions. Fifteen malignant mesothelioma (MM) effusions and 18 surgical HGSC specimens from the ovary were studied for comparative purposes. Palladin protein expression by immunohistochemistry was analysed in another series consisting of 261 HGSC effusions.
Results:
PALLD mRNA was significantly overexpressed in HGSC compared to MM effusions (P < .001). Palladin expression by immunohistochemistry was found in HGSC cells in 106/261 (41%) effusions, most commonly focally (<5% of cells). PALLD expression was additionally higher in ovarian HGSC specimens compared to HGSC effusions (P < .001). However, immunohistochemistry showed only stromal expression of this protein in surgical specimens. PALLD mRNA expression in HGSC effusions was unrelated to clinicopathological parameters, chemotherapy response or survival. Palladin protein expression was higher in post-chemotherapy, mainly disease recurrence, specimens compared to chemo-naïve effusions tapped at diagnosis (P = .018), although it was unrelated to other clinicopathological parameters or survival.
Conclusion:
PALLD mRNA is overexpressed in HGSC compared to MM effusions, and its protein product is overexpressed in post-chemotherapy compared to pre-chemotherapy HGSC effusions, suggesting upregulation along tumour progression. The presence of this molecule in HGSC effusions, at the mRNA or the protein level, is unrelated to disease outcome.
Insights
Palladin mRNA is overexpressed in high-grade serous carcinoma (HGSC) effusions compared to malignant mesothelioma (MM). Palladin protein is higher in post-chemotherapy HGSC effusions but does not impact patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Palladin is an actin-associated molecule implicated in cellular processes.
- Understanding its role in gynecological cancers is crucial for therapeutic development.
Purpose of the Study:
- To investigate the expression of palladin in high-grade serous carcinoma (HGSC) effusions.
- To determine the clinical significance of palladin in HGSC.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (RT-qPCR) for PALLD mRNA analysis.
- Immunohistochemistry for palladin protein expression.
- Analysis of HGSC and malignant mesothelioma (MM) effusions and surgical specimens.
Main Results:
- PALLD mRNA was significantly overexpressed in HGSC effusions versus MM effusions.
- Palladin protein expression was detected in 41% of HGSC effusions, often focally.
- Palladin protein was higher in post-chemotherapy HGSC effusions compared to chemo-naïve effusions.
Conclusions:
- PALLD mRNA is overexpressed in HGSC compared to MM.
- Palladin protein expression increases in HGSC effusions after chemotherapy.
- Palladin expression levels in effusions do not correlate with clinicopathological parameters or survival.
