[1520] Increased FLK-1, PDGFR-α, and BRAF Expression in Hepatocellular Carcinoma: An Immunohistochemical Molecular Mediator Survey.

Maria A Delgado, Xiaosong Li, Sameer H Patel, Peter J Kneuertz, N Volkan Adsay, Cynthia Cohen, Shishir K Maithel, Alton B Farris. Emory University Hospital, Atlanta, GA

Background: Hepatocellular carcinoma (HCC) pathogenesis is thought to be related to a number of molecular mediators, many of which are involved in vascular neogenesis. FLK-1, a vascular endothelial growth factor receptor, and platelet derived growth factor receptors (PDGFR)-α and -β activate signal transduction pathways that stimulate angiogenesis. BRAF is a serine/threonine protein kinase that regulates cellular growth, proliferation and survival. We hypothesized that HCC would exhibit overexpression of these molecular mediators compared to normal liver.
Design: Patients without prior treatment for HCC, who underwent resection from 8/00-3/08, were identified in our clinical and pathology databases. Routinely stained sections were reviewed; and histologic features of the tumor were analyzed, including tumor grade and histologic type. Sections with HCC in relation to non-neoplastic liver were selected. Slides were immunohistochemically stained for FLK-1, PDGFR-α, PDGFR-β, and BRAF. Staining intensities of the tumor and non-neoplastic liver were separately graded on a 5-tier scale from 0-4. The difference in staining expression was analyzed by a matched-pair T-test, with a P-value <0.05 considered significant.
Results: Fifty-seven cases were available for review. Mean patient age was 62.3 ± 11.8 years old (± standard deviation); 65% were male. Tumors exhibited a variety of grades (Grade 1, 2, 3 and 4: 0, 46, 47 and 7 % of cases, respectively) and histologic subtypes (predominantly trabecular, with a minority of other types). There was significantly higher expression of FLK-1, PDGFR-α, and BRAF compared to surrounding non-neoplastic liver [Table]. There was not a statistically significant difference in expression between different tumor grades or histologic subtypes.

Expression of Molecular Mediators in HCC

	Tumoral expression (Mean ± S.D.)	Non-neoplastic tissue expression (Mean ± S.D.)	P-value
Flk-1	2.8±0.9	2.1±0.7	<0.0001
PDGFR-α	2.4±0.8	1.9±0.7	0.0005
PDGFR-β	1.5±0.9	1.5±0.6	0.5
BRAF	0.9±0.6	0.2±0.4	<0.0001

S.D.: standard deviation


Conclusions: FLK-1, PDGFR-a, and BRAF expression are significantly increased in HCC compared to surrounding non-neoplastic liver, suggesting that the expression of these molecules is altered in hepatocellular carcinogenesis. These findings may help to select patients who would benefit from targeted inhibitor therapy.
Category: Liver & Pancreas

Monday, February 28, 2011 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 198, Monday Morning