Hypoxia-Inducible Gene 2 (HIG2) Protein – Novel Hypoxia Marker for Primary and Metastatic Renal Cell Carcinoma
M Tretiakova, M Hall, T Smertenko, E Hyjek, H Al-Ahmadie. University of Chicago, Chicago; Leica, Newcastle, United Kingdom; Memorial Sloan-Kettering Cancer Center, New York
Background: Tumor viability and progression is partly dependant on its response and adaptation to hypoxic conditions resulting from tumor growth. Clear cell renal cell carcinoma (CCRCC) is characterized by rich vascularity induced via hypoxia-inducible factor/mTOR pathways. Successes in treating CCRCC are largely attributed to molecular targeting of factors in these pathways, which is also being tried in other subtypes of RCC. HIG2 is a recently identified hypoxia-inducible growth factor that has not been well studied in renal tumors, and may be an option for targeted therapy in these tumors. Here we examined HIG2 expression in a large set of primary and metastatic RCC using a novel monoclonal antibody.
Design: Tissue microarray sections of 155 primary and 57 metastatic CCRCC (including 18 matched pairs), 76 papillary (PRCC) and 53 chromophobe (ChRCC) renal carcinomas, 24 oncocytomas (ONC) and 41 normal tissues from different organs were stained with HIG2 antibody (clone HX34Y, Leica). Reactivity with >5% of cells was considered positive. IHC intensity was scored as weak (1+), moderate (2+) or strong (3+).
Results: Detailed HIG2 expression is shown in Table 1. In primary CCRCC and PRCC 92% and 67% of cases expressed HIG2 with mean intensity of 2.14 and 1.49, respectively (p<0.01). In ChRCC and ONC, HIG2 was expressed in only 8% and 4% of cases with mean intensity of 0.11 and 0.08, respectively. In metastatic CCRCC, HIG2 was expressed in 91% of cases with mean intensity of 2.05. In 18 cases of matched primary and metastatic CCRCC, HIG2 was expressed in both sites in 14 cases with similar pattern and intensity, negative in both sites in 3 cases and positive in the metastasis only in 1 case.
|CCRCC primary (n=155)||12 (8%)||30 (19%)||44 (28%)||69 (45%)|
|CCRCC met (n=57)||5 (9%)||11 (19%)||16 (28%)||25 (44%)|
|PRCC (n=76)||25 (33%)||10 (13%)||20 (26%)||21 (28%)|
|ChRCC (n=53)||49 (92%)||2 (4%)||2 (4%)||0|
|ONC (n=24)||23 (96%)||0||1 (4%)||0|