Florid Lobular Carcinoma In-Situ (FLCIS): Molecular Profiling and Comparison to Classic LCIS (CLCIS) and Pleomorphic LCIS (PLCIS)
SJ Shin, PP Rosen, A Lal, S DeVries, J Suzuki, R Roy, E Hwang, SJ Schnitt, F Waldman, YY Chen. Weill Cornell Med College, NY, NY; UCSF, San Francisco, CA; Beth Israel Deaconess Med Ctr, Boston, MA
Background: Lobular carcinoma in-situ (LCIS) shows a range of morphologic variants including CLCIS, PLCIS and apocrine (apo) PLCIS. Classification & management for these subtypes remain problematic. Molecular profiling of LCIS subtypes may reveal relationships of these subtypes within the lobular neoplastic pathway. FLCIS is a distinct subtype characterized by classic type LCIS cells with direct involvement/marked expansion of ducts, central necrosis, calcifications, and increased frequency of concurrent invasive carcinoma (invca). Although the morphologic and immunohistochemical features of FLCIS have been described, its molecular profile has not yet been reported.
Design: Genomic alterations were evaluated on 20 cases of FLCIS using array-based comparative genomic hybridization (aCGH) with BAC arrays. Biomarker expression was examined by immunostaining for E-cadherin (E-cad), ER and cyclin D1. The genetic characteristics of FLCIS were compared to those of 20 CLCIS and 21 PLCIS (including 8 apo) from our previously published data performed on a similar aCGH platform.
Results: Similar to CLCIS and PLCIS, FLCIS was characterized by 1q gain (80%) and 16q loss (100%). Other recurrent genomic alterations observed in FLCIS included loss of 11q (50%), 17p (40%) and 8p (25%), and amplification including the cyclin D1 gene at 11q13.3 (25%). All 20 cases were E-cad negative and 19 (95%) were strongly positive for ER. Cyclin D1 expression was higher in cases with cyclin D1 gene amplification. Compared to CLCIS, FLCIS displayed significantly more fraction genome loss (4.6% v. 2.2%, p=0.007), more chromosomal breakpoints (11.6 v. 5.9, p=0.002) and higher numbers of amplifications (2.10 v. 0.15, p=0.03). FLCIS cases also showed significantly more chromosome breakage than PLCIS (p=0.04), and similar genetic complexity as seen in apo PLCIS.
Conclusions: FLCIS shares the cytologic features, E-cad loss and the lobular genetic signature of 1q gain and 16q loss found in CLCIS. However, these lesions demonstrate more genomic alterations than CLCIS. Our data support the conclusion that FLCIS is a genetically more advanced lesion than CLCIS. This may explain the greater frequency of concurrent invca in FLCIS than in CLCIS. These alternations also lend support for clinically managing this variant of LCIS more like DCIS than CLCIS.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 43, Tuesday Morning