CD10 (MME) Upregulation Is Commonly Associated with Hepatocellular Carcinoma Related to Hepatitis C Virus Infection and Chemoembolization
Lili Lee, Umut Sarpel, Martin Ligr, Cristina Hajdu, Margaret Cho, Max Xiangtian Kong, Qinghu Ren, Peng Lee, Ruliang Xu. New York University School of Medicine, New York
Background: Downregulation of CD10, also known as membrane metalloendopeptidase (MME), has been shown to be associated with liver metastasis and accelerated tumor growth in colorectal cancer. However, CD10 dysregulation may differ in subsets of hepatocellular carcinoma (HCC) due to the genetic heterogeneity related to variable etiologies and treatments of HCC. This study investigates CD10 expression in HCC and assesses whether rates of expression are affected by viral etiology (HBV and HCV) or chemoembolization (CE).
Design: A total of 86 liver explants and resection specimens for HCC were collected from NYU Langone Medical Center and Bellevue Hospital Center. The cases were categorized based on the type of associated viral infection (HBV vs. HCV), presurgical treatment (with or without CE), tumor focality, size, differentiation, the presence or absence of necrosis, vascular invasion, and patient gender and age. Neoplastic and paired non-neoplastic liver tissue was microdissected and total RNA was extracted from formalin-fixed, paraffin-embedded tissue. The rate of expression of CD10 was measured by quantitative RT-PCR using primers for the CD10 gene. Fischer's exact test was used for statistical analysis.
Results: Downregulation of CD10 expression was observed in 63% (54/86) of HCC cases, and upregulation was seen in only 24% (17/86) of HCC cases. In HCCs without presurgical treatment, there was a high percentage of downregulation (87.2%; 34/39) and a low percentage of upregulation (12.8%; 5/39). However, after CE, there was a significant decrease in the percentage of cases with downregulation (62.5%; 20/32) and an increase in those with upregulation (37.5%; 12/32) (p<0.05). Independently, compared to HBV-related HCCs, HCV-related HCCs had a significantly lower percentage of downregulation (57.1%; 12/21 vs. 85.1%; 23/27, respectively) and a higher percentage of upregulation (42.9%; 9/21 vs. 14.8%; 4/27, respectively) (p<0.05). No statistical difference was observed in CD10 expression when compared by tumor focality, tumor size, differentiation, necrosis, vascular invasion, or in gender and age.
Conclusions: Chemoembolization appears to upregulate CD10 expression in a subset of HCCs. HCV-related HCCs are less likely to have downregulation of CD10 as opposed to those related to HBV. The findings suggest that chemoembolization may change HCC's biologic behavior by upregulation of CD10 and also demonstrate a molecular difference between HCV and HBV-related HCCs.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 244, Tuesday Morning