PD-L1, Mismatch Repair Protein, and NTRK Immunohistochemical Expression in Cervical Small Cell Neuroendocrine
Longyun Chen1, Fan Yang1, Ting Feng1
1Department of Pathology, State Key Laboratory of Complex Severe and Rare Disease, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
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.
Insights
PD-L1 expression may be a therapeutic target in cervical small cell neuroendocrine carcinoma (SCNC). This study found SCNC tumors are MMR-stable and lack NTRK gene fusions, suggesting IHC is unreliable for detecting these fusions.
Area of Science:
- Oncology
- Pathology
- Genetics
Background:
- Cervical small cell neuroendocrine carcinoma (SCNC) is a rare, aggressive cancer with limited treatment options.
- Programmed Death-Ligand 1 (PD-L1) inhibitors and neurotrophin receptor tyrosine kinase (NTRK) inhibitors are potential pan-cancer therapies.
Purpose of the Study:
- To investigate PD-L1 expression and NTRK gene fusions in cervical SCNC.
- To evaluate the potential of PD-L1 as a therapeutic target and the reliability of immunohistochemistry (IHC) for NTRK fusion detection.
Main Methods:
- Immunohistochemistry (IHC) was used to detect PD-L1 and pan-Trk expression.
- Fluorescence in situ hybridization (FISH) and real-time polymerase chain reaction (RT-PCR) were used to confirm NTRK gene fusions in IHC-positive cases.
Main Results:
- PD-L1 expression was detected in 51.16% of patients, associated with higher proliferation but not improved survival in initial analysis.
- All tested cases were microsatellite instability-stable (MMR-stable) and lacked NTRK gene fusions.
- While 32.56% of cases showed pan-Trk expression by IHC, FISH and RT-PCR did not confirm NTRK gene fusions.
Conclusions:
- PD-L1 may represent a viable therapeutic target for cervical SCNC.
- Cervical SCNC is characterized by MMR-stable status and absence of NTRK gene fusions.
- IHC is not a reliable method for detecting NTRK gene fusions in cervical SCNC.
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