[166] Lobular Carcinoma Progression Model: Immunohistochemical Analysis on Tissue Microarray

F Chen, J Cangiarella, L Chiriboga, F Darvishian. NYU-Langone Medical Center, New York, NY

Background: Lobular carcinoma in situ (LCIS) is generally considered a marker for higher risk. However, there is evidence to show the progression of LCIS to invasive lobular carcinoma (ILC) as the two share some similar genomic alterations including chromosome 16q loss and 1q gain. In this pilot study, our objective was to seek the role of several carcinogenic markers in the evolution and progression of the lobular carcinoma of the breast.
Design: We generated a tissue microarray (TMA) including cores from normal lobules, LCIS and ILC in each case. Immunohistochemical (IHC) antibodies for E-cadherin, β-catenin, IGF1, IGF2, EGFR, ER, PR, her2, BRCA1, BRCA2, MLH1, MSH2, p53, bcl-2 and cyclin D1 were applied to the sections made from the TMA paraffin blocks. We scored each of the three components (i.e. normal lobule, LCIS, ILC) in every core separately by adding the score for distribution (0-4) to the score for intensity (0-3) with a maximum score of 7. Scoring of her2 was performed according to the Dako scoring system.
Results: We randomly identified 39 cases diagnosed as ILC (mean age: 62.4 years). In all cases, the LCIS and ILC were completely negative for E-cadherin. Membranous β-catenin staining was observed in 79% of normal lobules, 12.8% of LCIS and 20.5% of ILCs. Cytoplasmic (Golgi pattern) β-catenin staining was observed in 0% of normal lobules, 18% of LCIS and 38% of ILCs. See table 1 for IHC analysis.

Immunohistochemical Scores

	Normal Lobules (mean)	LCIS (mean)	ILC (mean)
IGF1	4.6	5.2	5.4
IGF2	5.0	5.5	5.6
EGFR	0.4	0	0
BRCA1	5.2	5.4	5.4
BRCA2	2.9	1.8	2.4
MLH1	3.2	3.9	3.8
MSH2	5.4	5.3	5.8
p53	0	0	0.3
cyclin D1	0	0.2	0.2
ER	2.2	3.7	3.6
PR	1.7	2.2	2.5
her2	0	0.1	0.1
bcl2	3.7	4.0	4.2

Maximum score=7; her2 score: 0-3

See table 2 for the clinicopathologic data.

Clinicopathologic Data

Laterality	Left	Right
	21 (53%)	18 (47%)
Subtype	Classical ILC	Pleomorphic ILC
	34 (87%)	5 (13%)
pT	T1	T2	T3
	20 (51%)	16 (41%)	3 (8%)
pN	N0	N1	N2	N3
	21 (53%)	12 (31%)	3 (8%)	3 (8%)
LVI	Present	Absent
	8 (20%)	31 (80%)

ILC: Invasive lobular carcinoma; LVI: Lymphovascular invasion


Conclusions: BRCA1, BRCA2, MLH1 and MSH2 are intact in lobular carcinoma. No diffuse overexpression of p53, EGFR, her2 or cyclin D1 is noted in lobular carcinoma. ER and PR are more frequently expressed in LCIS and ILC than normal lobules. IGF1, IGF2 and bcl-2 show slight incremental values from normal lobules to ILC. Incremental abnormal β-catenin staining was observed in LCIS and ILC.
Category: Breast

Tuesday, March 23, 2010 9:30 AM

Poster Session III # 42, Tuesday Morning