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Histological patterns and intra-tumor heterogeneity as prognostication tools in high grade serous ovarian cancers

  • Eros Azzalini
    Affiliations
    DSM- Department of Medical Sciences, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy

    IRCCS CRO Aviano-National Cancer Institute, Via Gallini 2, 33081 Aviano, Italy
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  • Renzo Barbazza
    Affiliations
    DSM- Department of Medical Sciences, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy
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  • Giorgio Stanta
    Affiliations
    DSM- Department of Medical Sciences, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy
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  • Giorgio Giorda
    Affiliations
    IRCCS CRO Aviano-National Cancer Institute, Via Gallini 2, 33081 Aviano, Italy
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  • Lucia Bortot
    Affiliations
    Unit of Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, PN, Italy

    DAME - Department of Medicine, University of Udine, Via Colugna 50, 33100 Udine, Italy
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  • Michele Bartoletti
    Affiliations
    Unit of Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, PN, Italy

    DAME - Department of Medicine, University of Udine, Via Colugna 50, 33100 Udine, Italy
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  • Fabio Puglisi
    Affiliations
    Unit of Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, PN, Italy

    DAME - Department of Medicine, University of Udine, Via Colugna 50, 33100 Udine, Italy
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  • Vincenzo Canzonieri
    Correspondence
    Corresponding author at: DSM- Department of Medical Sciences, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy.
    Affiliations
    Pathology Unit, IRCCS CRO Aviano-National Cancer Institute, Via Gallini 2, 33081 Aviano, Italy

    DSM- Department of Medical Sciences, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy
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  • Serena Bonin
    Correspondence
    Corresponding author at: DSM- Department of Medical Sciences, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy.
    Affiliations
    DSM- Department of Medical Sciences, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy
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Published:September 30, 2021DOI:https://doi.org/10.1016/j.ygyno.2021.09.012

      Highlights

      • In HGSOCs the definition of morphological architectural patterns and intratumor heterogeneity are useful in prognosis.
      • HGSOCs with SET features had longer overall and progression free survival
      • The Shannon diversity index (SDI) is a proposed method to measure intratumor heterogeneity.
      • In HGSOCs higher intratumor heterogeneity by SDI was a negative independent prognostic factor in patients treated with NACT.

      Abstract

      Objective

      High grade serous ovarian carcinoma (HGSOC) is the most common type of malignant ovarian neoplasm and the main cause of ovarian cancer related deaths worldwide. Although novel biomarkers such as homologous recombination deficiency testing have been implemented into the clinical decision-making algorithm since diagnosis, morphological classification and immunohistochemistry analysis are essential for diagnostic purpose. This study aims at identifying histologic and clinical features that can be predictive of patients' prognosis.

      Methods

      Morphological and architectural characterization including SET (Solid-Endometroid-Transitional)/Classic features was carried out in a cohort of 234 patients analyzing 695 slides. From each slide tumor infiltrating lymphocyte (TILs), the presence of necrosis, the number of mitoses, the presence of psammoma bodies, giant cells and atypical mitoses were recorded. Morphological heterogeneity was quantified by the Shannon's diversity index (SDI) considering the percentage of each architectural pattern per patient's slide.

      Results

      The frequency of architectural patterns and morphological variables varied with respect of the surgical strategy (primary debulking surgery vs interval surgery after neoadjuvant chemotherapy). HGSOCs exhibiting SET features had a longer overall as well as progression free survival. Among SET features, pseudo-endometrioid and transitional like patterns had the best outcome, while it was heterogenous for solid pattern, that had better outcome for BRCA 1 negative and less heterogeneous tumors. In patients submitted to neoadjuvant chemotherapy a higher intratumor heterogeneity as defined by SDI was a negative independent prognostic factor.

      Conclusions

      A comprehensive histological examination considering architectural patterns and their heterogeneity can help in prognostication of HGSOCs.

      Keywords

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