Florid lobular carcinoma in situ: molecular profiling and comparison to classic lobular carcinoma in situ and pleomorphic lobular carcinoma in situ

SummaryWe evaluated genomic alterations and biomarker expression in 20 florid lobular carcinomas in situ using array-based comparative genomic hybridization and immunohistochemical analysis. The genetic characteristics of florid lobular carcinoma in situ were compared with 20 classic lobular carcinomas in situ and 21 pleomorphic lobular carcinomas in situ (which included 8 apocrine variants), from our previously published data performed on a similar array-based comparative genomic hybridization platform. All 20 florid lobular carcinoma in situ cases were E-cadherin negative, and 92% were positive for estrogen receptor. Cyclin D1 expression correlated significantly negatively with estrogen receptor expression and was higher in cases with cyclin D1 (CCND1) gene amplification. Compared with classic lobular carcinoma in situ, florid lobular carcinoma in situ displayed significantly more fraction genome alteration (mean, 0.109 versus 0.072; P = .007), fraction genome loss (mean, 0.06 versus 0.03; P = .007), numbers of breakpoints (mean, 11.55 versus 6.95; P = .002), numbers of chromosome with breakpoints (mean, 5.85 versus 3.8; P = .004), and higher numbers of amplifications (mean, 2.10 versus 0.25; P = .03). Interestingly, florid lobular carcinoma in situ had the same genetic complexity as apocrine pleomorphic lobular carcinoma in situ. Our study demonstrated that florid lobular carcinoma in situ shares the cytologic features, E-cadherin loss, and the lobular genetic signature of 1q gain and 16q loss found in classic lobular carcinoma in situ. However, this variant demonstrates more genomic alterations than classic lobular carcinoma in situ and shares the same genetic complexity as apocrine pleomorphic lobular carcinoma in situ. Our data support the conclusion that florid lobular carcinoma in situ is genetically more advanced compared with the indolent phenotype of classic lobular carcinoma in situ. This may explain the greater frequency of concurrent invasive carcinoma in florid lobular carcinoma in situ compared with classic lobular carcinoma in situ.