Eosinophilic Cells as a Distinct Morphological Feature in <i>BRAF<sup>V600E</sup></i>-Mutated Ovarian Serous Borderline Tumors
<b>Background/Objectives</b>: According to recent reports, the <i>BRAF<sup>V600E</sup></i> mutation in serous borderline tumors (SBTs) plays a protective role against progression to low-grade serous carcinoma through oncogene-induced senescence. One consequence of...
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2025-06-01
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| author | Alina Badlaeva Anna Tregubova Aleksandra Asaturova Gennady Sukhikh |
| author_facet | Alina Badlaeva Anna Tregubova Aleksandra Asaturova Gennady Sukhikh |
| author_sort | Alina Badlaeva |
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| description | <b>Background/Objectives</b>: According to recent reports, the <i>BRAF<sup>V600E</sup></i> mutation in serous borderline tumors (SBTs) plays a protective role against progression to low-grade serous carcinoma through oncogene-induced senescence. One consequence of this is the appearance of eosinophilic cells (ECs). The aim of the current study was to determine the interobserver reproducibility of ECs and their predictive significance for the detection of the <i>BRAF<sup>V600E</sup></i> mutation in SBTs. <b>Methods</b>: The study was conducted using 63 cases of ovarian SBTs. Three gynecological pathologists, blinded to each tumor’s mutation status, assessed the presence of ECs. Immunohistochemical staining with p16 and Ki-67 was performed to validate ECs. Mutational analysis was carried out using targeted NGS. <b>Results</b>: Genetic analysis revealed 30 <i>BRAF</i>-mutated, 1 <i>NRAS</i>-mutated, and 9 <i>KRAS</i>-mutated SBTs. ECs were identified by the majority of pathologists (two or three) in 78% of the <i>BRAF<sup>V600E</sup></i>-mutated and 11% of the wild-type tumors with other mutations (<i>p</i> < 0.0001). The interobserver reproducibility of the presence of ECs was substantial (κ = 0.66). ECs validated with p16/Ki-67 were identified in 92.6% of the <i>BRAF<sup>V600E</sup></i>-mutated and in 13.8% of the wild-type tumors with other mutations (<i>p</i> < 0.0001). For the ECs identified by the majority of pathologists, the sensitivity and specificity when predicting the <i>BRAF<sup>V600E</sup></i> mutation were 77.8% and 88.9%, respectively. For the ECs validated with p16/Ki-67, the sensitivity and specificity when predicting the <i>BRAF<sup>V600E</sup></i> mutation were 95.3% and 90.5%, respectively. <b>Conclusions</b>: Overall, these results suggest that ECs in SBTs have potential association with the <i>BRAF<sup>V600E</sup></i> mutation. |
| format | Article |
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| spelling | doaj-art-2b148da3b0bf4ee4a93d4ef2cca9b2632025-08-20T02:24:38ZengMDPI AGDiagnostics2075-44182025-06-011512147910.3390/diagnostics15121479Eosinophilic Cells as a Distinct Morphological Feature in <i>BRAF<sup>V600E</sup></i>-Mutated Ovarian Serous Borderline TumorsAlina Badlaeva0Anna Tregubova1Aleksandra Asaturova2Gennady Sukhikh3National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of the Ministry of Health of Russia, Bldg. 4, Oparina Street, 117513 Moscow, RussiaNational Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of the Ministry of Health of Russia, Bldg. 4, Oparina Street, 117513 Moscow, RussiaNational Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of the Ministry of Health of Russia, Bldg. 4, Oparina Street, 117513 Moscow, RussiaNational Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of the Ministry of Health of Russia, Bldg. 4, Oparina Street, 117513 Moscow, Russia<b>Background/Objectives</b>: According to recent reports, the <i>BRAF<sup>V600E</sup></i> mutation in serous borderline tumors (SBTs) plays a protective role against progression to low-grade serous carcinoma through oncogene-induced senescence. One consequence of this is the appearance of eosinophilic cells (ECs). The aim of the current study was to determine the interobserver reproducibility of ECs and their predictive significance for the detection of the <i>BRAF<sup>V600E</sup></i> mutation in SBTs. <b>Methods</b>: The study was conducted using 63 cases of ovarian SBTs. Three gynecological pathologists, blinded to each tumor’s mutation status, assessed the presence of ECs. Immunohistochemical staining with p16 and Ki-67 was performed to validate ECs. Mutational analysis was carried out using targeted NGS. <b>Results</b>: Genetic analysis revealed 30 <i>BRAF</i>-mutated, 1 <i>NRAS</i>-mutated, and 9 <i>KRAS</i>-mutated SBTs. ECs were identified by the majority of pathologists (two or three) in 78% of the <i>BRAF<sup>V600E</sup></i>-mutated and 11% of the wild-type tumors with other mutations (<i>p</i> < 0.0001). The interobserver reproducibility of the presence of ECs was substantial (κ = 0.66). ECs validated with p16/Ki-67 were identified in 92.6% of the <i>BRAF<sup>V600E</sup></i>-mutated and in 13.8% of the wild-type tumors with other mutations (<i>p</i> < 0.0001). For the ECs identified by the majority of pathologists, the sensitivity and specificity when predicting the <i>BRAF<sup>V600E</sup></i> mutation were 77.8% and 88.9%, respectively. For the ECs validated with p16/Ki-67, the sensitivity and specificity when predicting the <i>BRAF<sup>V600E</sup></i> mutation were 95.3% and 90.5%, respectively. <b>Conclusions</b>: Overall, these results suggest that ECs in SBTs have potential association with the <i>BRAF<sup>V600E</sup></i> mutation.https://www.mdpi.com/2075-4418/15/12/1479serous borderline tumorBRAFKRASNRASeosinophilic cellsoncogene-induced senescence |
| spellingShingle | Alina Badlaeva Anna Tregubova Aleksandra Asaturova Gennady Sukhikh Eosinophilic Cells as a Distinct Morphological Feature in <i>BRAF<sup>V600E</sup></i>-Mutated Ovarian Serous Borderline Tumors Diagnostics serous borderline tumor BRAF KRAS NRAS eosinophilic cells oncogene-induced senescence |
| title | Eosinophilic Cells as a Distinct Morphological Feature in <i>BRAF<sup>V600E</sup></i>-Mutated Ovarian Serous Borderline Tumors |
| title_full | Eosinophilic Cells as a Distinct Morphological Feature in <i>BRAF<sup>V600E</sup></i>-Mutated Ovarian Serous Borderline Tumors |
| title_fullStr | Eosinophilic Cells as a Distinct Morphological Feature in <i>BRAF<sup>V600E</sup></i>-Mutated Ovarian Serous Borderline Tumors |
| title_full_unstemmed | Eosinophilic Cells as a Distinct Morphological Feature in <i>BRAF<sup>V600E</sup></i>-Mutated Ovarian Serous Borderline Tumors |
| title_short | Eosinophilic Cells as a Distinct Morphological Feature in <i>BRAF<sup>V600E</sup></i>-Mutated Ovarian Serous Borderline Tumors |
| title_sort | eosinophilic cells as a distinct morphological feature in i braf sup v600e sup i mutated ovarian serous borderline tumors |
| topic | serous borderline tumor BRAF KRAS NRAS eosinophilic cells oncogene-induced senescence |
| url | https://www.mdpi.com/2075-4418/15/12/1479 |
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