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HER2 status as a potential predictive biomarker for ovarian clear cell carcinoma

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BARTU KENDALL Michaela NEMEJCOVA Kristyna MICHALKOVA Romana STRUZINSKA Ivana HAJKOVA Nikola HOJNY Jan KRKAVCOVA Eva LACO Jan MATEJ Radoslav DROZENOVA Jana MEHES Gabor FABIAN Pavel HAUSNEROVÁ Jitka SVAJDLER Marian SKAPA Petr CIBULA David ZIMA Tomas DUNDR Pavel

Rok publikování 2023
Druh Článek v odborném periodiku
Časopis / Zdroj Virchows Archiv
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www https://link.springer.com/article/10.1007/s00428-023-03640-4
Doi http://dx.doi.org/10.1007/s00428-023-03640-4
Klíčová slova HER2; Ovarian clear cell carcinoma; Immunohistochemistry; Gynecopathology; Ovarian cancer
Popis Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian carcinoma characterized by unique biological features and highly malignant characteristics including low chemosensitivity. Therefore, new therapeutic targets are needed. These could include the downstream pathways of receptor tyrosine kinases, especially the human epidermal growth factor receptor 2 (HER2). Our main objective was to characterize the HER2 status using immunohistochemistry (IHC) and FISH on 118 OCCCs, also considering the novel paradigm of HER2-zero and HER2-low status. Other aims included determination of the association between HER2 status and survival, HER2 gene DNA and RNA NGS analysis, HER2 gene expression analysis, and correlation between IHC and gene expression in HER2-zero and HER2-low cases. Cases with HER2 overexpression/amplification accounted for 5.1% (6/118), with additional 3% harbouring HER2 gene mutation. The remaining 112 (94.9%) cases were HER2-negative. Of these, 75% were classified as HER2-zero and 25% as HER2-low. This percentage of HER2 aberrations is significant concerning their possible therapeutic influence. Cases from the HER2-zero group showed significantly better survival. Although this relationship lost statistical significance in multivariate analysis, the results have potential therapeutic significance. HER2 gene expression analysis showed a significant correlation with HER2 IHC status in the entire cohort (HER2-positive vs. HER2-negative), while in the cohort of only HER2-negative cases, the results did not reach statistical significance, suggesting that gene expression analysis would not be suitable to confirm the subdivision into HER2-low and HER2-zero. Our results also emphasize the need for standardized HER2 testing in OCCC to determine the best predictor of clinical response.

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