PD‐L1, PARP1, and MMRs as potential therapeutic biomarkers for neuroendocrine cervical cancer
| Autor: | Lei Sui, Han Zhao, Qin Yao, Kejuan Song, Xiaoyu Ji, Teng Lv |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_treatment Poly (ADP-Ribose) Polymerase-1 Uterine Cervical Neoplasms PARP1 B7-H1 Antigen Targeted therapy 0302 clinical medicine Molecular Targeted Therapy Stage (cooking) Immune Checkpoint Inhibitors RC254-282 Mismatch Repair Endonuclease PMS2 Original Research Cervical cancer biology Neoplasms. Tumors. Oncology. Including cancer and carcinogens Middle Aged targeted therapy DNA-Binding Proteins MutS Homolog 2 Protein Treatment Outcome 030220 oncology & carcinogenesis Immunohistochemistry Female Microsatellite Instability immunotherapy MutL Protein Homolog 1 Adult medicine.medical_specialty 03 medical and health sciences PD-L1 Internal medicine Biomarkers Tumor medicine Humans Radiology Nuclear Medicine and imaging Aged Chemotherapy business.industry Clinical Cancer Research Microsatellite instability Immunotherapy medicine.disease mismatch repair proteins neuroendocrine cervical cancer Carcinoma Neuroendocrine 030104 developmental biology PD‐L1 biology.protein Neoplasm Recurrence Local Tumor Suppressor Protein p53 business |
| Zdroj: | Cancer Medicine, Vol 10, Iss 14, Pp 4743-4751 (2021) Cancer Medicine |
| ISSN: | 2045-7634 |
| Popis: | Objective Neuroendocrine cervical cancer (NECC) is a rare cervical cancer with high aggressivity that causes poor prognosis even in the early stage. Given other neuroendocrine carcinomas and other types of cervical cancer have been proved to have expression of programmed cell death protein 1 ligand 1(PD‐L1) and poly ADP‐ribose polymerase‐1(PARP1), we would measure and analyze these proteins in this invasive cancer. The purpose of this study is to investigate the application value of PD‐1/PD‐L1 and PARP1 inhibitors in NECC. Methods The NECC cases in our center with formalin‐fixed paraffin‐embedded tissue blocks were collected, and immunohistochemical (IHC) staining of PD‐L1, PARP1, Mismatch repair proteins (MMRs), and P53 was performed. Chi‐square test was used to analyze associations between various protein expressions. We analyzed the efficacy of immunotherapy in a recent patient with secondary recurrence after two courses of chemotherapy. Results After rigorous screening, 20 cases were finally included. Three cases did not undergo surgical treatment because of their advanced stage. Twelve (60%) developed distant metastases or relapsed within five years, and most of them within two years. The positive rate of PD‐L1 and PARP1 were 70% and 75% respectively. Among all the cases, microsatellite instability (MSI) was seen in six cases (30%) and abnormal p53 expression was in 15 patients (75%). PD‐L1 was associated with PARP1 expression in the MSI subgroup. The patient treated with chemotherapy + VEGF inhibitor (VEGFi) + programmed cell death protein 1(PD‐1) inhibitor had an excellent improvement in clinical symptoms, tumor markers, and mass size. Conclusion The IHC results of PD‐L1, PARP1, and MMRs suggested that NECC was the target of immunotargeted therapy. Our case confirmed that immune checkpoint therapy was effective in patients with PD‐L1 positive and MMRs loss. Considering the clinical practicability, more cases should be collected, and effective biomarkers still need to be further searched. The feasible immunotargeted therapy for cervical neuroendocrine tumors was discussed by studying the expression of PD‐L1, PARP1, 4 kinds of mismatch repair proteins and p53 in cervical cancer and case analysis. |
| Databáze: | OpenAIRE |
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