Abstract P1-02-09: Results of a worldwide survey on the currently used histopathological diagnostic criteria for invasive lobular breast cancer (ILC)
Authors: De Schepper Maxim , Vincent-Salomon Anne , Christgen Matthias , Van Baelen Karen , Tsuda Hitoshi , Kurozumi Sasagu , Brito Maria Jose , Cserni Gabor , Schnitt Stuart , Larsimont Denis , Kulka Janina , Fernandez Pedro Luis , Rodriguez Paula , Aula Ana , Mendelez Cristina , Van Bockstal Mieke , Kovacs Aniko , Varga Zsuzsanna , Wesseling Jelle , Bhargava Rohit , Boström Pia , Franchet Camille , Zambuko Blessing , Matute Gustavo , Berghian Anca , van Diest Paul , Oesterreich Steffi , Derksen Patrick WB , Floris Giuseppe , Desmedt Christine 
Published: March 2022

Abstract
Background. ILC represents the second most common histological type of breast cancer (BC), accounting for approximately 15% of all invasive BCs. Loss of cell-cell adhesion due to genomic alterations of CDH1,. the gene coding for E-cadherin, is the hallmark of ILC. So far, in the WHO guidelines, it is essential to recognize the dispersed or linear discohesive cells but it is not mandatory to demonstrate E-cadherin loss by immunohistochemistry (IHC) for diagnosing ILC. Recent central pathology revisions of clinical trials have demonstrated overdiagnosis of ILC in local pathological diagnosis, as only ~60% of the locally diagnosed ILCs were confirmed by central pathology. To understand the possible underlying reasons, we undertook a worldwide survey on the currently used histopathological diagnostic criteria for ILC. Materials and Methods. A survey was drafted using the online tool SurveyMonkey by a panel of pathologists and researchers from the European Lobular Breast Cancer Consortium (ELBCC). This survey was circulated to pathologists from December 14, 2020 until July, 1 2021. The main goals were to register the use of E-cadherin as a diagnostic marker for ILC and the systematic reporting of the ILC subtypes. Results. A total of 149 entries were recorded from 34 different countries from 6 continents. Pathologists declared working in a large tertiary (30%, 44/149) or university hospital (56%, 84/149), with an average yearly volume of BC samples &gt;300 in 111/149 (74%) and &gt;500 in 80/149 (54%) respondents. 117/149 (79%) are specialized in breast pathology. About half of the pathologists systematically perform IHC for ILC diagnosis (52%, 77/149), whilst others only perform staining in case of doubt (43%, 64/149) or for differentiating DCIS from LCIS (3%, 4/149). There was no association between the systematic use of IHC, the volume of BC samples, the type of institution (academic, large tertiary, private), and the number of pathologists in the institution. Concerning the use of IHC, 141/145(97%) participants use E-cadherin, 35/145 (24%) use β-catenin and 49/145 (34%) use p120-catenin. The majority (50%, 73/145) uses only E-cadherin, 13% (19/145) use E-cadherin in combination with β-catenin or 23% (33/145) use E-cadherin with p120-catenin, while 11% (16/145) use all 3 antibodies. For E-cadherin, 11 different clones were reported, of which the NCH-38 is the most frequently used (45%, 39/86), followed by Clone 36 (17%, 15/86) and EP700Y (16%, 14/86). Heterogeneity is reported regarding the used concentration per clone. The most frequently used modality of antigen retrieval is the heat induced one. Similar findings were observed for β-catenin and p120-catenin with each 4 different clones reported, again with variable concentrations. Only 4/104 (4%) respondents reported to perform DNA sequencing for CDH1 for diagnosing ILC. Most special lobular types are systematically reported by the vast majority of the pathologists: classic (149/149, 100%), pleomorphic (140/149, 94%), solid (108/149, 72%), histiocytoid/apocrine (90/149, 60%), alveolar (90/149, 60%), trabecular (54/149, 36%), mixed non-classic (54/149, 36%) and mucinous (51/149, 34%). Conclusions. We report the results of the first worldwide survey concerning diagnosis of ILC in pathological practice. The results demonstrate that ~half of the institutions systematically perform E-cadherin IHC to support the diagnosis of ILC. There is a great variability in E-cadherin antibody clones used as well as their concentrations, which might result in differences in staining results and their interpretation. As ILC-specific therapeutic avenues are currently being explored, some of which already in the context of clinical trials, it is of utmost importance to further improve the standardization of ILC diagnosis at the pathology level.
Citation Format: Maxim De Schepper, Anne Vincent-Salomon, Matthias Christgen, Karen Van Baelen, Hitoshi Tsuda, Sasagu Kurozumi, Maria Jose Brito, Gabor Cserni, Stuart Schnitt, Denis Larsimont, Janina Kulka, Pedro Luis Fernandez, Paula Rodriguez, Ana Aula, Cristina Mendelez, Mieke Van Bockstal, Aniko Kovacs, Zsuzsanna Varga, Jelle Wesseling, Rohit Bhargava, Pia Boström, Camille Franchet, Blessing Zambuko, Gustavo Matute, Anca Berghian, Paul van Diest, Steffi Oesterreich, Patrick WB Derksen, Giuseppe Floris, Christine Desmedt. Results of a worldwide survey on the currently used histopathological diagnostic criteria for invasive lobular breast cancer (ILC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-02-09.