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).
|BH (n=11)||BA (n=5)||CC (n=8)||PE (n=10)||p-value (CC vs BA+BH)||p-value (CC vs benign)|
|Cases with p53 (2+)||1/11 (09%)||0/5 (0%)||7/8 (88%)||0/10 (10%)||0.0002||<0.0001|