Guillaume Bataillon1, Laetitia Fuhrmann1, Elodie Girard1, Emanuelle Menet2, Marick Laé1, Mathieu Capovilla3, Isabelle Treilleux4, Laurent Arnould5, Frederique Penault-Llorca6, Roman Rouzier7, Caterina Marchiò1,8, Ivan Bieche1, Anne Vincent-Salomon1. 1. Institut Curie, Paris Sciences Lettres Research University, Pôle de médecine diagnostique et théranostique, Paris, France. 2. Institut Curie, Versailles Saint Quentin University, Pôle de médecine diagnostique et théranostique, Saint-Cloud, France. 3. Department of Pathology, Centre François Baclesse, Caen, France. 4. Department of Pathology, Centre Léon-Bérard, Lyon, France. 5. Department of Pathology, Centre Georges François Leclerc, Dijon, France. 6. Department of Pathology, Centre Jean Perrin, Clermont-Ferrand, France. 7. Institut Curie, Versailles Saint Quentin University, Surgery Department, Saint-Cloud, France. 8. Department of Medical Sciences, University of Turin, Turin, Italy.
Abstract
AIMS: Low-grade adenosquamous carcinoma of the breast (LGASC) is a rare variant of metaplastic carcinoma characterised by a favourable outcome and histologically composed of glandular and squamous elements in a spindle cell background typically associated with a lymphocytic stromal reaction. Because of its rarity, the immunophenotypic and genetic profile of LGASC has not been sufficiently characterised. The aim of this study was to gain insights into the molecular and phenotypic characteristics of LGASC. METHODS AND RESULTS: We reviewed the clinical and morphological features and detailed the immunohistochemical characteristics of a retrospective series of 13 LGASCs. Targeted sequencing of 50 genes was performed in 10 of 13 cases. Identified mutations were further assessed by Sanger sequencing in a validation series of 11 additional cases. All tumours showed a triple-negative immunophenotype, expressed 'basal' keratins, showed variable levels of epidermal growth factor receptor expression, and did not express androgen receptor. Sequencing analysis of the screening set of LGASCs revealed a high rate (seven of 10 cases) of PIK3CA mutations, whereas no TP53 mutations were found. All PIK3CA mutations were missense mutations located either in exon 20 (n = 6) or in exon 9 (n = 1). The global PIK3CA mutation rate, including the validation series, was 52% (11 of 21 cases). No disease recurrences were observed. [Correction added on 11 June 2018, after first online publication: The percentage of mutation rate was corrected to 52%] CONCLUSIONS: Our results indicate that LGASC of the breast is a low-grade triple-negative breast cancer that harbours a basal-like phenotype with no androgen receptor expression, and shows a high rate of PIK3CA mutations but no TP53 mutations.
AIMS: Low-grade adenosquamous carcinoma of the breast (LGASC) is a rare variant of metaplastic carcinoma characterised by a favourable outcome and histologically composed of glandular and squamous elements in a spindle cell background typically associated with a lymphocytic stromal reaction. Because of its rarity, the immunophenotypic and genetic profile of LGASC has not been sufficiently characterised. The aim of this study was to gain insights into the molecular and phenotypic characteristics of LGASC. METHODS AND RESULTS: We reviewed the clinical and morphological features and detailed the immunohistochemical characteristics of a retrospective series of 13 LGASCs. Targeted sequencing of 50 genes was performed in 10 of 13 cases. Identified mutations were further assessed by Sanger sequencing in a validation series of 11 additional cases. All tumours showed a triple-negative immunophenotype, expressed 'basal' keratins, showed variable levels of epidermal growth factor receptor expression, and did not express androgen receptor. Sequencing analysis of the screening set of LGASCs revealed a high rate (seven of 10 cases) of PIK3CA mutations, whereas no TP53 mutations were found. All PIK3CA mutations were missense mutations located either in exon 20 (n = 6) or in exon 9 (n = 1). The global PIK3CA mutation rate, including the validation series, was 52% (11 of 21 cases). No disease recurrences were observed. [Correction added on 11 June 2018, after first online publication: The percentage of mutation rate was corrected to 52%] CONCLUSIONS: Our results indicate that LGASC of the breast is a low-grade triple-negative breast cancer that harbours a basal-like phenotype with no androgen receptor expression, and shows a high rate of PIK3CA mutations but no TP53 mutations.
Authors: Willard Wong; Edi Brogi; Jorge S Reis-Filho; George Plitas; Mark Robson; Larry Norton; Monica Morrow; Hannah Y Wen Journal: NPJ Breast Cancer Date: 2021-07-22
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