Carcinogenesis Pathways of Pleomorphic Lobular Carcinoma
Ihab Lamzabi, Ritu Ghai, Vijaya Reddy, Pincas Bitterman, Rohit Singh, Paolo Gattuso. Rush University Medical Center, Chicago, IL
Background: Pleomorphic lobular carcinoma (PLC) is an aggressive variant of lobular carcinoma. Several studies have compared the clinical and morphologic features of classical lobular carcinoma to that of PLC. However, sparse literature is available regarding the molecular characteristics of PLC. The aim of this study was to investigate the molecular pathways behind the biologic behavior of PLC.
Design: Cases negative for E-Cadherin and with morphologic features of PLC were identified from our surgicsal pathology files for the period 2004 and 2012. Pertinent clinicopathological features were reviewed. A panel of immunostains including estrogen receptors (ER), progesterone receptors (PR), P16, CD117, CK5, vimentin, EGFR, p53, cyclin D1, and BCL-2 and fluorescence in situ hybridization (FISH) for HER-2 NEU were performed in all cases.
Results: A total of 35 cases were identified. The average age was 64 years. Twenty five patients were Caucasian, 9 African-American and 1 Asian. T1, T2, T3, and T4 stages were seen 11, 16, 5, and 3 cases respectively. Twenty one patients (60%) had lymph node metastases and 5 (14%) had distant metastases. HER-2 NEU was amplified by FISH in 4 cases (11%). Positivity for ER was seen in 31 cases (88%), PR in 22 cases (62%), cyclin D1 in 30 cases (85%), P16 in 24 cases (68%), CD117 in 7 cases (20%), vimentin and EGFR in 2 cases (5%) and for BCL-2 in 33 cases (94%) including 7 cases with partial loss of expression. P53 was expressed in 18 cases with strong 3+ positivity in only 7 cases (20%). Four triple negative cases were identified, of which only 2 were positive for EGFR and vimentin, strongly positive for CK5, P53 and CD117, lost BCL-2 expression indicating a basal-like type phenotype. Larger tumor size correlated with loss of BCL-2 (p=0.003), and loss of PR (p=0.01). Lymph node metastasis was associated with lack of expression of CD117 (p=0.08), and larger tumor size (p=0.02). Distant metastases were associated with higher P53 expression (p=0.03), high T stage (p=0.03), loss of PR (p=0.03) and non Caucasian ethnicity (p=0.02). Tumors from non Caucasian patients also showed higher P53 expression (p=0.02).
Conclusions: The carcinogenesis of PLC seems to involve aberrations in different pathways. BCL-2 appears to downregulate tumor growth. P53 mutation, CD117 expression as well as loss of PR seem to promote metastases. Non Caucasian patients seem to have higher risk of distant metastasis. Basal cell type has a distinctive immunoprofile which suggests a distinct carcinogenesis pathway. We also report a lower frequency of HER-2 NEU amplification by FISH in PLC than most published literature.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 31, Wednesday Afternoon