Characterization of CD34 Expression in Nonalcoholic Steatohepatitis
RM Gill, NM Bass, LD Ferrell. Univ Calif, San Francisco; Univ Calif, SF
Background: Non-alcoholic steatoheptitis (NASH) is increasing in incidence and is among the most prevalent liver diseases in the developed world. Correct classification of NASH liver biopsies is of critical importance and relies on correct orientation to microscopic liver architecture. Centrizonal arteries in NASH cases represent a potential source of diagnostic error and so, to better characterize this previously reported finding, we evaluated CD34 expression in NASH liver biopsies.
Design: 100 biopsies, with NASH fibrosis stage >1a, from NASH Clinical Research Network participants (2/05 - 8/06) were randomly selected, H&E stained slides were reviewed, and adjacent unstained sections were immunostained for CD34. Prevalence of CD34+ centrizonal microvessels was graded as 0 (none in central zones), 1 (1-2 central zones with microvessels), 2 (<50% of central zones with microvessels), or 3 (>50% of central zones with microvessels). Pericentral sinusoid CD34 immunostaining was also graded (0, 1, and 2) and lobular microvessels (MV) were quantified.
Results: Microvessels were present in portal tracts and lobular parenchyma in all cases and in central zones in 73/100 biopsies (in comparison, centrizonal arteries were identified in 40% of cases on H&E stained sections). Higher stage lesions demonstrated more prevalent central zone involvement by CD34+ microvessels (grades 2+3) [stage 1: 5/19 (26%); stage 2: 8/34 (24%); stage 3: 24/36 (67%); stage 4: 9/11 (82%)], with increasing prevalence correlating directly with more advanced disease (p < 0.001). Evaluation of pericentral sinusoid CD34 immunostaining (grades 1+2) revealed a similar significant association with higher stage lesions [stage 1: 13/19 (68%); stage 2: 26/34 (77%); stage 3: 32/36 (89%); stage 4: 10/11 (91%)] (p<0.001). Microvessel density in lobular parenchyma (stage 1: 1.5 +/- 0.23 MV/mm2; stage 2: 1.2 +/- 0.12 MV/mm2; stage 3: 2.2 +/- 0.2 MV/mm2; stage 4: 3.3 +/- 0.51 MV/mm2) was also significantly increased in advanced disease (p < 0.001).
Conclusions: Centrizonal arteries/microvessels are common in NASH and, along with sinusoidal capillarization, are notably increased in patients with higher NASH fibrosis stage. Pathologists should be aware of the possible finding of CD34+ centrizonal arteries/microvessels in higher stage cases and not fail to diagnose NASH. The finding of increased centrizonal arteries and sinusoidal capillarization in advanced stage NASH support an etiologic role for angiogenesis and/or vascular remodeling in NASH progression to cirrhosis.
Category: Liver & Pancreas
Monday, March 22, 2010 1:30 PM
Platform Session: Section D, Monday Afternoon