[1550] Dysplastic Biliary Lesions in Primary Sclerosing Cholangitis Harbor Cytogenetic Abnormalities Similar to Cholangiocarcinoma.

Sarah E Kerr, Emily G Barr Fritcher, Michael B Campion, Benjamin R Kipp, Jesse S Voss, Susan C Abraham, Kevin C Halling, Jason T Lewis. Mayo Clinic, Rochester, MN; The University of Texas MD Anderson Cancer Center, Houston

Background: Grading criteria for biliary dysplasia (biliary intraepithelial neoplasia, BilIN) have been recently described. This literature suggests a dysplasia-carcinoma sequence in which dysplasia is associated with concurrent or future cholangiocarcinoma (CCA), especially in primary sclerosing cholangitis (PSC). If so, cytogenetic abnormalities similar to those seen in CCA may be present in BilIN.
Design: Nine PSC liver explants in which a previous multi-section gross protocol had identified BilIN grade 3 were selected. One or two formalin fixed, paraffin embedded blocks from each patient represented the following lesions of interest: normal/reactive (N/R) biliary epithelium, intestinal metaplasia without dysplasia (IM), BilIN 1-2 (low grade dysplasia), BilIN 3 (high grade dysplasia), and CCA. Areas of interest were chosen by consensus of two pathologists and circled on H&E stained slides as a template for UroVysion^® fluorescence in situ hybridization (FISH probes to 9p21 and centromeres 3, 7, and 17). A cytotechnologist scored 50 consecutive well-visualized epithelial cells per lesion.
Results: Mean (range) % of cells with abnormality on a per lesion basis.

		FISH
HISTOLOGY	Lesions Counted	Hemiz. 9p21 Loss	Homoz. 9p21 Loss	Homoz. 9p21 Loss Only*	Single Locus Gain	Polysomy
N/R	7	14 (4-28)	3 (0-6)	3 (0-6)	5 (0-16)	0 (0-2)
IM	4	20 (6-26)	3 (2-4)	3 (2-24)	11 (0-36)	0 (0-0)
BilIN 1-2	11	32 (0-14)	15 (0-100)	5 (0-14)	5 (0-12)	15 (0-86)
BilIN 3	10	33 (0-56)	35 (0-100)	14 (0-62)	21 (2-38)	34 (0-70)
CCA	1	0 (0)	100 (100)	16 (16)	22 (22)	62 (62)

*Homozygous 9p21 loss as the only abnormality in the counted cell (i.e., not seen in combination with other gains or losses)
Conclusions: Polysomy, a finding strongly associated with CCA, is also detected in some PSC associated BilIN. Homozygous 9p21 loss is seen in some BilIN 3 and CCA. The percentage of abnormal cells is on average higher as the degree of histologic abnormality increases, supporting a dysplasia-carcinoma sequence. Furthermore, cases histologically interpreted as BilIN 1-2 may harbor worrisome cytogenetic abnormalities, while some lesions interpreted as BilIN 3 may not. Although the gold standard is not yet clear, these findings could have important implications for the interpretation of biliary cytology-based FISH.
Category: Liver & Pancreas

Wednesday, March 2, 2011 9:30 AM

Poster Session V # 197, Wednesday Morning