The phosphatase PTPN1/PTP1B is a candidate marker of better chemotherapy response in metastatic high-grade serous carcinoma

Objective: To analyze the expression and clinical role of the phosphatase PTPN1 (PTP1B) in serous effusions.

Methods: PTPN1 mRNA expression by quantitative RT-PCR was analyzed in 83 high-grade serous carcinoma (HGSC) and 15 malignant mesothelioma (MM) effusions. PTP1B and phospho-PTP1B (pPTP1B) protein expression by immunohistochemistry was analyzed in 62 HGSC and 44 MM effusions.

Results: PTPN1 mRNA (p=0.048), PTP1B protein (p=0.047) and pPTP1B protein (p<0.001) were overexpressed in HGSC compared to MM effusions. PTPN1 mRNA was additionally overexpressed in post-chemotherapy HGSC effusions compared to chemo-naïve effusions (p=0.005). However, pPTP1B protein expression was higher in effusions from patients with FIGO stage III compared to stage IV disease (p=0.006), and higher expression of both PTPN1 mRNA (p=0.041) and PTP1B protein (p=0.035) in HGSC effusions was associated with better (complete) chemotherapy response at diagnosis. PTPN1 RNA and protein expression was unrelated to survival in HGSC, whereas a trend for shorter overall survival (p=0.06) was found for MM patients whose tumors expressed pPTP1B protein.

Conclusion: PTPN1 is overexpressed in HGSC compared to MM effusions, and may be a marker of better chemotherapy response in the former. Whether PTPN1 activation is informative of adverse outcome in MM merits further investigation.

Keywords: PTPN1; effusion; high-grade serous carcinoma; malignant mesothelioma.