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. 2020 Jul;33(7):1287-1297.
doi: 10.1038/s41379-020-0459-6. Epub 2020 Jan 13.

Genomic profiling of pleomorphic and florid lobular carcinoma in situ reveals highly recurrent ERBB2 and ERRB3 alterations

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Free article

Genomic profiling of pleomorphic and florid lobular carcinoma in situ reveals highly recurrent ERBB2 and ERRB3 alterations

Beth T Harrison et al. Mod Pathol. 2020 Jul.
Free article

Abstract

Pleomorphic LCIS (P-LCIS) and florid LCIS (F-LCIS) are morphologic variants distinguished from classic LCIS by marked nuclear pleomorphism and/or an expansile growth pattern with or without necrosis. Given the rarity of these LCIS variants, little data exist regarding their molecular pathogenesis, natural history, and optimal management. The purpose of this study was to genomically profile LCIS variants to gain further insight into their biology. Nineteen cases of pure LCIS variants (17 P-LCIS, 2 F-LCIS) diagnosed on core needle biopsy at our institution from 2006 to 2017 were included, five of which were upgraded to invasive cancer at excision. Macrodissected lesions were analyzed by a hybrid-capture next generation sequencing assay that surveyed exonic sequences of 447 genes for mutations and copy number variations (CNVs) and 191 regions across 60 genes for structural rearrangements. LCIS variants were all confirmed as E-cadherin negative by immunohistochemistry. Receptor profiles among the 17 P-LCIS cases included HR+/HER2- (nine cases), HR+/HER2+ (three cases), HR-/HER2+ (two cases), and HR-/HER2- (three cases). The two F-LCIS cases were HR+/HER2- and HR+/HER2+. All LCIS variants had genetic alterations consistent with a lobular phenotype including 1q gain (16 cases), 16q loss (18 cases), and CDH1 mutations (18 cases). Highly recurrent ERBB2 alterations were noted including mutations (13 cases) and amplifications (six cases). Other significant alterations included mutations in PIK3CA (six cases), RUNX1 (four cases), ERBB3 (four cases), and CBFB (three cases), as well as amplification of CCND1 (five cases). A TP53 mutation was identified in one case of HR-/HER2+ P-LCIS with signet ring cell features that lacked 1q gain and 16q loss. P-LCIS and F-LCIS contain genetic alterations characteristic of lobular neoplasia; however, these LCIS variants are distinguished from classical LCIS reported in the literature by their highly recurrent ERBB2 alterations.

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References

    1. Foote FW, Stewart FW. Lobular carcinoma in situ: a rare form of mammary cancer. Am J Pathol. 1941;17:491–6.3. - PubMed - PMC
    1. Haagensen CD, Lane N, Lattes R, Bodian C. Lobular neoplasia (so-called lobular carcinoma in situ) of the breast. Cancer. 1978;42:737–69. - PubMed
    1. Dabbs DJ, Schnitt SJ, Geyer FC, Weigelt B, Baehner FL, Decker T, et al. Lobular neoplasia of the breast revisited with emphasis on the role of E-cadherin immunohistochemistry. Am J Surg Pathol. 2013;37:e1–11. - PubMed
    1. Canas-Marques R, Schnitt SJ. E-cadherin immunohistochemistry in breast pathology: uses and pitfalls. Histopathology. 2016;68:57–69. - PubMed
    1. National Comprehensive Cancer Network (US) Clinical practice guidelines in oncology, breast cancer (version 3.2019). Fort Washington, PA: National Comprehensive Cancer Network (US); 2019. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf . Accessed on 11/02/2019.

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