Image analysis of proliferating cell nuclear antigen expression and immunohistochemical profiles in renal cell carcinoma associated with acquired cystic kidney disease: comparison with classic renal cell carcinoma

Abstract

Renal cell carcinoma (RCC) arising in acquired cystic kidney disease (ACKD) is considered to be a tumor of low malignant potential, compared with classic RCC. The aim of the present study was to identify any significant differences in the antigenic profiles or tumor cell proliferative activity of ACKD-associated RCC and classic RCC that might be responsible for differences in their biologic behavior. We studied the immunohistochemical profiles and proliferative activity of 12 classic RCCs and 5 ACKD-associated RCCs with markers of proximal tubules (Leu M1, alpha-1 antitrypsin, CAM 5.2), markers of distal tubules (Arachis hypogaea lectin, AE1/AE3, epithelial membrane antigen [EMAJ, CAM 5.2), vimentin, and proliferating cell nuclear antigen (PCNA). We performed proliferation analysis with the CAS 200 image analysis system. For each case, 8 to 20 fields of tumor tissue in the areas of maximal PCNA staining were quantitated, and the percentage of PCNA-positive nuclear area for each individual tumor was calculated. All of the five ACKD-associated RCCs expressed AE1/AE3, EMA, and CAM 5.2 in more than 50% of the tumor cells. Arachis hypogaea lectin was significantly expressed in three of the five ACKD-associated RCCs. Leu M1 and alpha-1 antitrypsin reacted with fewer than 10% of the tumor cells in all of the five ACKD-associated RCCs. In contrast, the 12 classic RCCs showed expression of CAM 5.2 in 11 cases, alpha-1 antitrypsin in 10 cases, Leu M1 in 9, EMA in 8, and AE1/AE3 in 3 cases in more than 50% of the tumor cells and a totally negative reaction with Arachis hypogaea lectin in 8 cases, EMA in 4, AE1/AE3 in 4, and vimentin in 5 cases. Although coexpression of proximal and distal tubule markers was seen in some cases of RCC in either category, there was uniform and strong staining for distal tubule markers in ACKD-associated RCC and for proximal tubule markers in classic RCC. The mean percentage of PCNA-positive nuclear area for the ACKD-associated RCCs (2.41%) was significantly (P < .05) less than that of the classic RCCs (21.42%). The differences in expression of proximal and distal tubule markers and proliferative activity might be responsible for the differences in the biologic behavior of ACKD-associated RCC and classic RCC.