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Application of precision medicine based on next-generation sequencing and immunohistochemistry in ovarian cancer: a
Yoo-Na Kim1, Yun Soo Chung1, Ji Hyun Lee1
1Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Objective:
To evaluate the landscape of gene alterations and immunohistochemistry (IHC) profiles of patients with ovarian cancer for targeted therapy and investigate the real-world experience of applying precision medicine.
Methods:
Patients diagnosed with ovarian cancer between January 2015 and May 2021 at Severance Hospital and who underwent tumor next-generation sequencing (NGS) were reviewed. Data on germline mutation, IHC markers for mismatch repair deficiency (MMRd), programmed death ligand 1 (PD-L1) expression, and human epidermal growth factor receptor 2 (HER2) expression were acquired. The use of matched therapy and its clinical outcomes were evaluated.
Results:
Of the 512 patients who underwent tumor NGS, 403 underwent panel-based germline testing. In patients who underwent both tests, tumor NGS identified 39 patients (9.7%) with BRCA mutations and 16 patients (4.0%) with other homologous recombination repair (HRR)-associated gene mutations, which were not found in germline testing. The most common single nucleotide variants were TP53 (82.2%), ARID1A (10.4%), PIK3CA (9.7%), and KRAS (8.4%). Copy number aberrations were found in 122 patients. MMRd was found in 3.2% of patients, high PD-L1 expression in 10.1%, and HER2 overexpression in 6.5%. Subsequently, 75 patients (14.6%) received a poly (ADP-ribose) polymerase inhibitor based on BRCA mutation and 11 patients (2.1%) based on other HRR-associated gene mutations. Six patients (1.2%) with MMRd underwent immunotherapy. Twenty-eight patients (5.5%) received other matched therapies targeting HER2, fibroblast growth factor receptor, folate receptor alpha, RAS, and PIK3CA.
Conclusion:
A comprehensive review of germline mutation, IHC, and tumor NGS helped identify candidates for precision therapy in patients with ovarian cancer, a proportion of whom received matched therapy.
Insights
This study analyzed gene alterations and immunohistochemistry profiles in ovarian cancer patients to guide targeted therapy. Precision medicine application identified candidates for matched therapies, improving treatment strategies.
Area of Science:
- Oncology
- Genetics
- Precision Medicine
Background:
- Ovarian cancer treatment can be advanced by understanding gene alterations and immunohistochemistry (IHC) profiles.
- Precision medicine offers tailored therapeutic strategies based on individual patient molecular characteristics.
Approach:
- Retrospective review of 512 ovarian cancer patients undergoing tumor next-generation sequencing (NGS) and germline testing.
- Analysis of gene mutations (e.g., BRCA, HRR-associated genes, TP53), IHC markers (MMRd, PD-L1, HER2), and matched therapy outcomes.
Key Points:
- Tumor NGS identified BRCA mutations in 9.7% and other HRR-associated mutations in 4.0% of patients, with TP53, ARID1A, PIK3CA, and KRAS as common variants.
- Mismatch repair deficiency (MMRd) was observed in 3.2%, high PD-L1 in 10.1%, and HER2 overexpression in 6.5% of patients.
- 14.6% received PARP inhibitors for BRCA/HRR mutations, 1.2% received immunotherapy for MMRd, and 5.5% received other targeted therapies.
Conclusions:
- Integrating germline, IHC, and tumor NGS data is crucial for identifying ovarian cancer patients eligible for precision therapy.
- A significant proportion of patients received matched therapies based on molecular profiling, demonstrating the real-world application of precision medicine.
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