Immunohistochemical expression of cytochrome P4A11 (CYP4A11), carbonic anhydrase 9 (CAIX) and Ki67 in renal cell carcinoma; diagnostic relevance and relations to clinicopathological parameters.

ABSTRACT

BACKGROUND: Cytochrome P4A11 (CYP4A11) is a member of cytochrome p450 family, which is involved in arachidonic acid metabolism that participates in promoting malignant cell proliferation, progression, and angiogenetic capacity. Carbonic Anhydrase 9 (CAIX) is a transmembrane protein that plays an integral part in regulating hypoxia which affects cancer cell metabolism, proliferation and promotes metastasis. The aim of this study was to evaluate the immunohistochemical expression of CYP4A11, CAIX and ki67 in RCC subtypes in relation to clinicopathological parameters and to evaluate the diagnostic significance of CYP4A11 and CAIX in differentiating renal cell carcinoma (RCC) subtypes. MATERIALS AND METHODS: one hundred primary RCC cases, collected from Pathology Department, Faculty of Medicine, Tanta University and from private laboratories, were evaluated for immunohistochemical expression of CYP4A11, CAIX and ki67. RESULTS: CYP4A11 was expressed in 59% of RCC; with 91.7% sensitivity and 90% specificity in differentiating clear cell and non-clear cell subtypes. CAIX was expressed in 50% of RCC; with 95% sensitivity, 80% specificity. High expression of CYP4A11 was statistically positively associated with higher tumor grade, high expression of CAIX was statistically positively associated with lower tumor grade and absence of necrosis and high ki67 labeling index was significantly associated with clear cell subtype, larger tumor sizes, higher tumor grade, advanced tumor stage, fat invasion and vascular invasion. CONCLUSIONS: CYP4A11 and CAIX can be used as diagnostic markers to differentiate clear cell RCC from other subtypes. CYP4A11 is more diagnostically accurate and specific than CAIX. High expression of CYP4A11, low CAIX expression and high ki67 labeling index were related to features of aggressive tumor behavior.