[1760] Comparison of Hepatocellular Markers for Diagnosis of Poorly-Differentiated Hepatocellular Carcinoma: High Sensitivity with Combined Use of Arginase-1 and Glypican-3

Daniel GK Phillips, Dhanpat Jain, Michael Torbenson, Tsung-Teh Wu, Matthew MC Yeh, Sanjay Kakar. University of California, San Francisco, San Francisco, CA; Yale-New Haven Hospital, New Haven, CT; The Johns Hopkins Hospital, Baltimore, MD; Mayo Clinic, Rochester, MN; University of Washington, Seattle, WA

Background: Evidence-based use of immunohistochemistry is important in poorly-differentiated liver tumors,especially when limited tissue is available. Commonly used hepatocellular markers like Hep Par 1(Hep) and polyclonal carcinoembryonic antigen(pCEA) have low sensitivity for poorly differentiated HCC(PD-HCC). This study compares the efficacy of four hepatocellular markers in HCC.
Design: Immunohistochemistry for Hep,pCEA, glypican-3(GPC) and arginase-1(Arg) was done on well-(WD),moderately- differentiated(MD) and PD-HCC cases (n=75). In 13 cases,there was >1 differentiation pattern,which were scored separately yielding 88 observations. Staining intensity of 2+ or 3+ (scale 0-3) in >5% of tumor cells was considered positive.
Results: Arg and Hep had the highest sensitivity for WD-HCC,while Arg and GPC had the highest sensitivity for PD-HCC. When staining of >50% of tumor was considered positive,Arg was the most sensitive marker for all differentiations. The addition of Hep or pCEA to Arg did not lead to increased sensitivity. Combined use of Arg and GPC yielded 100% sensitivity for PD-HCC. When staining of >50% of tumor was considered positive,the sensitivity of combined Arg and GPC was 94%.

Table 1

	Arginase-1	Glypican-3	HepPar-1	pCEA
Well-differentiated (n=13)	100/100	61/15	100/100	92/77
Moderately-differentiated (n=40)	100/98	82/60	98/83	88/65
Poorly-differentiated (n=35)	97/80	85/74	63/31	60/17

Numbers stated as a/b reflect percentages; a-positivity in >5% of tumor, b-positivity in ≥ 50% of tumor

Table 2

	Hep+GPC	Hep+Arg	GPC+Arg
Well-differentiated (n=13)	100/100	100/100	100/100
Moderately-differentiated (n=40)	100/98	100/98	100/100
Poorly-differentiated (n=35)	97/85	97/80	100/94

Numbers stated as a/b reflect percentages; a-positivity for at least one marker in >5% of tumor, b-positivity for at least one marker in ≥ 50% of tumor


Conclusions: Arg is the most sensitive marker for all differentiations of HCC. For WD and MD-HCC, addition of other hepatocellular markers to Arg does not significantly improve sensitivity. GPC is of limited value in WD and MD-HCC, but has high sensitivity for PD-HCC. Its combined use with Arg identified all cases of PD-HCC with >50% staining in tumor cells in nearly all cases, indicating that this combination will be helpful in needle biopsies.
Category: Liver

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 249, Tuesday Morning