PD-L1, Mismatch Repair Protein, and NTRK Immunohistochemical Expression in Cervical Small Cell Neuroendocrine Carcinoma

Abstract

Background Cervical small cell neuroendocrine carcinoma (SCNC) is a rare and aggressive disease that lacks a standard treatment strategy or effective methods of targeted therapy. PD-L1 inhibitors for DNA mismatch repair system-deficient (dMMR) tumors and neurotrophin receptor tyrosine kinase (NTRK) inhibitors offer potential pan-cancer treatments. Methods Immunohistochemistry was employed as the main detection method, and any NTRK positive cases, identified by immunohistochemistry, were further submitted for evaluation by fluorescence in situ hybridization (FISH) and real-time polymerase chain reaction (RT-PCR) methods. Results Forty-six patients were enrolled. Positive PD-L1 expression was seen in 22 of the 43 patients (51.16%) with an average combined positive score of 6.82. PD-L1-positive patients were more likely to have a higher proliferation rate in the tumor, and they experienced less recurrence and death (p = 0.048 and 0.033, respectively) compared with the patients with negative PD-L1 expression. However, in the multivariate analysis, none of the clinical parameters was associated with the expression of PD-L1. There was no association between PD-L1 expression and disease recurrence or overall survival in the Kaplan-Meier analysis. All cases were found to be MMR-stable and lacked NTRK gene fusion. However, pan-Trk expressed in 14 (32.56%) of the 43 tested cases, but FISH and RT-PCR failed to confirm any positive fusion signals in IHC-positive cases. Conclusions PD-L1 may be an effective therapeutic target for cervical SCNC. Cervical SCNC is a MMR-stable tumor and lacks NTRK gene fusion. IHC isn’t a reliable method in the detection of NTRK gene fusion in cervical SCNC.