Tumor-infiltrating lymphocytes are the key determinants of pathological features associated with pathogenic BRCA variants in high-grade serous ovarian carcinoma Article Swipe
Dang H Nguyen-Phan
,
Thao Dang
,
Anh Kim Dang
,
Lynn Huynh
,
Phuong Anh Nguyen
,
Vu Tran
,
Hanh Thi Tuyet Ngo
,
Thao Doan
,
Tu Anh Thai
,
Chien‐Chin Chen
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3389/fmed.2025.1555883
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3389/fmed.2025.1555883
Background High-grade serous ovarian carcinoma (HGSOC), an aggressive cancer associated with pathogenic BRCA variants, causes genomic instability and sensitivity to poly (ADP-ribose) polymerase inhibitors. Identifying pathogenic BRCA variants is crucial for the treatment of HGSOC; however, genetic testing is expensive and time-consuming. This study aimed to explore pathological features, particularly the presence of tumor-infiltrating lymphocytes (TILs), as potential surrogates to streamline patient selection for genetic testing. Methods We retrospectively analyzed 58 cases of HGSOC with known BRCA variant profiles. Tumors were categorized as TIL-positive or TIL-negative based on the presence of > 40 or ≤ 40 intraepithelial lymphocytes in a single high-power field (HPF), respectively. Key pathological features, including solid, endometrioid, and transitional (SET) architecture patterns; necrosis; and mitotic activity, were evaluated within these subgroups. Statistical analyses were used to determine the associations between these features and BRCA variant status. Results In TIL-negative HGSOCs, SET patterns were strongly associated with pathogenic or likely pathogenic BRCA variants ( p = 0.028), emerging as the most reliable morphological marker in this group. In TIL-positive HGSOCs, low mitotic activity (≤7 mitotic figure per 10 HPFs) was significantly correlated with pathogenic BRCA variants ( p = 0.0002), underscoring its diagnostic significance. Necrosis and mitotic activity in TIL-negative cases and SET patterns in TIL-positive cases were not significantly associated with pathogenic BRCA variants. Combined analysis of both TIL subgroups diluted these associations, underscoring the significance of stratifying cases by the immune context. Discussion The presence of TILs affects the diagnostic value of pathological features for BRCA variant status in HGSOC. Regarding pathogenic BRCA variants, SET patterns and low mitotic activity were identified as critical markers in TIL-negative tumors and TIL-positive tumors, respectively. These associations likely stem from interactions among genomic instability, immune response, and tumor growth. Our framework leverages these insights to prioritize high-risk cases for genetic testing, thereby optimizing resource allocation. Conclusion The presence of TILs is critical for understanding the association between pathological features and pathogenic BRCA variants in HGSOC. To improve pathogenic BRCA variant prediction, optimize genetic testing, and guide tailored intervention, our framework integrates immune context and morphological markers. This approach is especially useful in resource-limited settings and can enhance diagnostic efficiency and clinical decision-making.
Related Topics
Concepts
Serous fluid
Pathological
Ovarian carcinoma
Serous carcinoma
Carcinoma
Medicine
Cancer research
Oncology
Pathology
Biology
Ovarian cancer
Internal medicine
Cancer
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fmed.2025.1555883
- https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1555883/pdf
- OA Status
- gold
- References
- 41
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4410994229
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4410994229Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3389/fmed.2025.1555883Digital Object Identifier
- Title
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Tumor-infiltrating lymphocytes are the key determinants of pathological features associated with pathogenic BRCA variants in high-grade serous ovarian carcinomaWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-06-03Full publication date if available
- Authors
-
Dang H Nguyen-Phan, Thao Dang, Anh Kim Dang, Lynn Huynh, Phuong Anh Nguyen, Vu Tran, Hanh Thi Tuyet Ngo, Thao Doan, Tu Anh Thai, Chien‐Chin ChenList of authors in order
- Landing page
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https://doi.org/10.3389/fmed.2025.1555883Publisher landing page
- PDF URL
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https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1555883/pdfDirect link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
- OA URL
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https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1555883/pdfDirect OA link when available
- Concepts
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Serous fluid, Pathological, Ovarian carcinoma, Serous carcinoma, Carcinoma, Medicine, Cancer research, Oncology, Pathology, Biology, Ovarian cancer, Internal medicine, CancerTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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41Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.sensitivity | 18 |
| abstract_inverted_index.stratifying | 231 |
| abstract_inverted_index.(ADP-ribose) | 21 |
| abstract_inverted_index.TIL-negative | 85, 142, 202, 271 |
| abstract_inverted_index.TIL-positive | 83, 171, 208, 274 |
| abstract_inverted_index.architecture | 114 |
| abstract_inverted_index.associations | 132, 278 |
| abstract_inverted_index.instability, | 285 |
| abstract_inverted_index.interactions | 282 |
| abstract_inverted_index.particularly | 49 |
| abstract_inverted_index.pathological | 47, 106, 247, 319 |
| abstract_inverted_index.significance | 229 |
| abstract_inverted_index.transitional | 112 |
| abstract_inverted_index.underscoring | 193, 227 |
| abstract_inverted_index.associations, | 226 |
| abstract_inverted_index.endometrioid, | 110 |
| abstract_inverted_index.intervention, | 339 |
| abstract_inverted_index.morphological | 165, 346 |
| abstract_inverted_index.respectively. | 104, 276 |
| abstract_inverted_index.significance. | 196 |
| abstract_inverted_index.significantly | 183, 212 |
| abstract_inverted_index.understanding | 315 |
| abstract_inverted_index.intraepithelial | 96 |
| abstract_inverted_index.retrospectively | 68 |
| abstract_inverted_index.time-consuming. | 41 |
| abstract_inverted_index.decision-making. | 363 |
| abstract_inverted_index.resource-limited | 354 |
| abstract_inverted_index.tumor-infiltrating | 53 |
| cited_by_percentile_year | |
| countries_distinct_count | 2 |
| institutions_distinct_count | 10 |
| citation_normalized_percentile.value | 0.2673251 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |