[1761] Collagen Immunohistochemical Stains in the Liver Are Useful in Differentiating Capsular from Septal Fibrosis

Jonathan B Rock, Martha M Yearsley, Adam J Hanje, Wendy L Frankel. The Ohio State University Medical Center, Columbus, OH

Background: Cirrhosis is a significant cause of morbidity and mortality with increasing incidence worldwide. While progress has been made in clinical and radiographic diagnosis of cirrhosis, core needle biopsy (CBx) remains essential. It is not unusual to receive severely fragmented CBx, particularly when significant fibrosis is present. The distinction between capsular/subcapsular (Cap) fibrosis and true septal (Sep) fibrosis can be challenging in fragmented CBx, leading to potential over-staging of fibrosis. Collagens and glycoproteins are natural components of hepatic parenchyma, which accumulate in varying proportions as hepatic fibrosis progresses. We evaluated the utility of staining for collagen types and common glycoproteins in differentiating Cap from Sep fibrosis.
Design: Consecutive explanted cirrhotic livers (15) were identified and whole-sections containing adequate Cap and Sep fibrosis were stained for Vitronectin, Orcein, Laminin, Trichrome and Collagens III, IV, V and VI. Staining was graded as negative (0), weak (1) or strong (2). Statistical analysis was performed using a paired T-test. To attempt to mimic the clinical problem of CBx with fragmentation, CBx were obtained from 5 additional explanted cirrhotic livers with inked capsules using an 18-gauge biopsy needle. These were evaluated as previously described.
Results:

Staining Patterns in Cap and Sep Fibrosis in Whole Sections
  Collagen IIICollagen IVCollagen VCollagen VIVitronectinOrcein
Sep Fibrosisstrong1414015912
 weak110043
 negative0015020
Cap Fibrosisstrong60371315
 weak61010810
 negative352010
p-value 0.0012<0.0001<0.00010.00130.23770.0824


Collagen III, IV and VI showed statistically decreased staining in Cap compared to Sep fibrosis. Collagen V showed statistically increased staining in Cap compared to Sep fibrosis. Orcein and trichrome were strong regardless of location. Laminin was consistently negative in both regions, but was helpful in identifying the layer of mesothelial cells overlying the capsule. Vitronectin showed the greatest degree of heterogeneity. Analysis of 5 CBx showed that decreased Collagen III, IV and VI and increased Collagen V distinguished Cap from Sep fibrosis with at least 2 of these staining patterns noted in each CBx. Collagens IV and V were the most useful discriminators.
Conclusions: Immunohistochemical staining for collagens III, IV, V and VI show distinct staining patterns in Cap and Sep fibrosis, which can be helpful to distinguish these areas even on small fragmented biopsies.
Category: Liver

Wednesday, March 21, 2012 9:30 AM

Poster Session V # 245, Wednesday Morning

 

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