title: Genetic and phenotypic characteristics of pleomorphic lobular carcinoma in situ of the breast.
abstract: The clinical, pathologic, and molecular features of pleomorphic lobular carcinoma in situ (PLCIS) and the relationship of PLCIS to classic LCIS (CLCIS) are poorly defined. In this study, we analyzed 31 cases of PLCIS (13 apocrine and 18 nonapocrine subtypes) and compared the clinical, pathologic, immunophenotypic, and genetic characteristics of these cases with those of 24 cases of CLCIS. Biomarker expression was examined using immunostaining for E-cadherin, gross cystic disease fluid protein-15, estrogen, progesterone, androgen receptor, human epidermal growth factor receptor2, CK5/6, and Ki67. Array-based comparative genomic hybridization to assess the genomic alterations was performed using microdissected formalin-fixed paraffin-embedded samples. Patients with PLCIS presented with mammographic abnormalities. Histologically, the tumor cells were dyshesive and showed pleomorphic nuclei, and there was often associated necrosis and microcalcifications. All lesions were E-cadherin negative. Compared with CLCIS, PLCIS showed significantly higher Ki67 index, lower estrogen receptor and progesterone receptor expression, and higher incidence of HER2 gene amplification. The majority of PLCIS and CLCIS demonstrated loss of 16q and gain of 1q. Apocrine PLCIS had significantly more genomic alterations than CLCIS and nonapocrine PLCIS. Although lack of E-cadherin expression and the 16q loss and 1q gain-array-based comparative genomic hybridization pattern support a relationship to CLCIS, PLCIS has clinical, mammographic, histologic, immunophenotypic, and genetic features that distinguish it from CLCIS. The histologic features, biomarker profile, and genomic instability observed in PLCIS suggest a more aggressive phenotype than CLCIS. However, clinical follow-up studies will be required to define the natural history and most appropriate management of these lesions.
authors.affiliation: Department of Pathology, University of California San Francisco, California 94143, USA. yunn-yi.chen@ucsf.edu
authors.forename: Yunn-Yi
authors.initials: YY
authors.lastname: Chen
authors.forename: Eun-Sil Shelley
authors.initials: ES
authors.lastname: Hwang
authors.forename: Ritu
authors.initials: R
authors.lastname: Roy
authors.forename: Sandy
authors.initials: S
authors.lastname: DeVries
authors.forename: Joseph
authors.initials: J
authors.lastname: Anderson
authors.forename: Chrystal
authors.initials: C
authors.lastname: Wa
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Fitzgibbons
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Jacobs
authors.forename: Gaetan
authors.initials: G
authors.lastname: MacGrogan
authors.forename: Hans
authors.initials: H
authors.lastname: Peterse
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent-Salomon
authors.forename: Taku
authors.initials: T
authors.lastname: Tokuyasu
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Schnitt
authors.forename: Frederic M
authors.initials: FM
authors.lastname: Waldman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D016130:Immunophenotyping; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
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