[1771] Immunohistochemical Analysis of Six1 in Hepatocellular Carcinoma: Correlation with Proliferation, Prognostic Parameters, and Outcome

Jason Wang, Diane Lawson, Cynthia Cohen. Emory University, Atlanta

Background: The incidence of hepatocellular carcinoma (HCC) is increasing, both in the U.S. and worldwide. Homeobox genes encode transcription factors which act as regulators of development. Six1 is one such homeobox gene and is overexpressed in breast, ovarian, hepatocellular, and cervical cancers. Increased Six1 protein expression, detected by Western blot, has been shown to be significantly correlated with pTNM stage, vascular invasion, and poor overall survival.
Design: 135 HCCs in 3 tissue microarrays with 2 1mm cores of each tumor were assessed for Six1 expression by immunohistochemistry (IHC). Stains, scored as intensity 0-3+ and nuclear vs cytoplasmic labeling, were compared to proliferation (mitoses/10HPF, MIB-1 visual mean and high, phosphohistone-3[PPH3] visual mean and high), prognostic parameters (size, grade, stage, vascular invasion, metastases, focality), and outcome (recurrence, survival).
Results: Of the 135 HCCs, 108 (77%) had 2-3+ nuclear Six1 expression, 62 (44%) had 3+ nuclear Six1 expression, 78 (56%) had 2-3+ cytoplasmic Six1 expression, and 30 (21%) had 3+ cytoplasmic Six1 expression.
Significant correlations are summarized below:

Significant Correlations
 Direct Significancep-value
Six1 nuclear (2-3+)Mitoses0.001
Six1 nuclear (3+)Size0.01
 MIB Visual High0.001
 MIB Visual Mean0.001
 PPH3 Visual High0.003
 PPH3 Visual Mean<0.001
 Nuclear Grade0.05
 pT Stage0.02
 Vascular Invasion0.03
 Recurrencesee Figure 1
Six1 cytoplasmic (2-3+)Nuclear Grade0.04
 Distant Metastasis0.03
 Recurrencesee Figure 2
Six1 cytoplasmic (3+)Size0.002
 MIB Visual High0.03
 Histologic Grade<0.001
 Nuclear Grade<0.001

Figure 1:

Figure 2:

Conclusions: We demonstrate that strong Six1 positivity by IHC is significantly correlated with increased proliferation, worse prognosis (larger tumor size, higher nuclear grade, histologic grade, and pT stage, and increased vascular invasion and distant metastases), and increased recurrence.
Category: Liver

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 245, Tuesday Morning


Close Window