Expression of Carbonic Anhydrase IX in Genitourinary and Adrenal Tumors.
Daniel P Donato, Matthew T Johnson, Ximing J Yang, Debra L Zynger. The Ohio State University Medical Center, Columbus; Northwestern University, Chicago, IL
Background: Carbonic anhydrase IX (CAIX) expression is inducible by hypoxia through HIF 1-alpha, and is involved in cell adhesion, cell proliferation, tumor progression and mitigation of intracellular pH. High expression has been described in malignancies of the genitourinary tract including renal cell carcinoma (RCC), clear cell type. We investigated the expression of CAIX in needle biopsies and resections of the genitourinary tract, including organs with limited prior studies such as prostate, testis and adrenal gland.
Design: Sections from 436 tumors (renal cortex, n=130; bladder/renal pelvis/ureter, n=124; prostate, n=67; testis, n=52; adrenal, n=63) including 34 needle biopsies and 31 types of neoplasms were incubated with CAIX. Immunoreactivity was semi-quantitatively evaluated (0, <5% of cells stained; 1+, 5-10%; 2+, 11-50%; or 3+, >50%) and intensity was graded (0 to 3).
Results: Of the 14 types of renal cortical tumors tested, expression was predominately restricted to clear cell RCC (59/60), papillary RCC (8/10) and clear cell papillary RCC (1/1). Core biopsies of RCC clear cell were positive (25/25) and cores with angiomyolipoma, translocation RCC and oncocytoma were negative (0/5). Approximately half of the cases of urothelial carcinoma were positive (39/81) with expression in squamous, small cell, sarcomatoid and adenomatous differentiation but not signet ring or plasmacytoid variants. Pure urothelial tract adenocarcinoma (2/2), squamous cell carcinoma (6/8) and clear cell adenocarcinoma (3/3) were frequently positive. Only rare cases of prostatic adenocarcinoma expressed CAIX (3/66). Testicular germ cell and sex cord stomal tumors showed variable reactivity (seminoma, 0/10; yolk sac tumor, 0/10; embryonal carcinoma, 2/7; choriocarcinoma, 2/4; teratoma, 2/7; Leydig cell tumor, 0/2; Sertoli cell tumor, 2/3). CAIX was demonstrated in adrenal cortical carcinoma (6/11) and pheochromocytoma (2/11). Adrenal cortical adenoma (3/11) and non-neoplastic adrenal tissue (12/30) showed weak cytoplasmic reactivity, unlike all other tumors positive for CAIX which had membranous expression.
Conclusions: CAIX is a very sensitive marker for clear cell RCC, both in resections and core biopsies. However, CAIX also shows high expression in genitourinary tumors which can have a clear cell appearance such as urothelial and squamous cell carcinoma as well as adrenal cortical carcinoma and Sertoli cell tumor. Although non-neoplastic adrenal and adrenal cortical adenoma had CAIX reactivity, it was typically weak and cytoplasmic, unlike the expression seen in clear cell RCC.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 123, Monday Morning