[1738] Ki-67 and p53 Expression as an Immunohistochemical Tool in the Differential Diagnosis of Benign and Malignant Biliary Lesions

Gregor Krings, Linda Ferrell, Ryan Gill. Univ Calif, San Francisco

Background: Benign biliary lesions may morphologically and immunophenotypically mimic well-differentiated cholangiocarcinoma (CC), leading to diagnostic dilemmas, especially in small biopsies. High proliferative index (PI) as determined by Ki-67 staining and p53 expression are often considered as evidence in support of malignancy in various diagnostic settings. However, systematic assessment of the expression of these markers and evidence-based evaluation of their potential utility in differentiating benign from malignant biliary lesions has not been reported.
Design: Immunostains for Ki-67 and p53 were performed on resection and biopsy specimens of CC (n=8), biliary hamartoma (BH; n=11), biliary adenoma (BA; n=5), and parenchymal extinction (PE; n=10). PI and p53 staining was calculated by quantifying the highest percentage of positive tumor nuclei per section. Staining intensity was scored as 0 (negative), 1+ (weak), or 2+ (strong).
Results: The PI as determined by Ki-67 staining ranged from 10.1-39.9% with a mean of 19.4 ± 9.7% in CC, which was significantly increased compared to BH (1.0±1.5%), BA (0.7±1.0%) and PE (0.4±0.3%). All CC but no benign lesions demonstrated a PI exceeding 10%. Total p53 expression (5.9±5.4%) varied from 0.2-17.7% in CC and was significantly increased with respect to BH (1.2±1.9%), BA (0.0±0.1%) and PE (2.9±5.2%). Strong (2+) p53 staining was present in 7 (88%) of 8 CC cases but only 1 (4%) of 26 benign lesions (p<0.0001).

Ki-67 and p53 staining in biliary lesions
 BH (n=11)BA (n=5)CC (n=8)PE (n=10)p-value (CC vs BA+BH)p-value (CC vs benign)
Ki-67 (%)1.0±1.50.7±1.019.4±9.70.4±0.3<0.0001<0.0001
p53 (%)1.2±1.90.0±0.15.9±5.42.9±5.20.0020.008
Cases with p53 (2+)1/11 (09%)0/5 (0%)7/8 (88%)0/10 (10%)0.0002<0.0001



Conclusions: CC display a significantly increased proliferative index in contrast to BA, BH, and PE, and a threshold of 10% positive Ki-67 nuclei differentiated CC from benign lesions. Similarly, p53 expression is significantly increased in CC versus benign lesions, and strong p53 staining may be seen in nearly all CC cases but only rarely in benign lesions and can be used as a specific marker for malignancy in this context. Addition of Ki-67 and p53 to the immunohistochemical panel may therefore facilitate distinction of CC from benign biliary lesions.
Category: Liver

Tuesday, March 20, 2012 1:00 PM

Poster Session IV # 235, Tuesday Afternoon

 

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