Overexpression of carbonic anhydrase IX (CAIX) in vulvar cancer is associated with tumor progression and development of locoregional lymph node metastases

Abstract

Carbonic anhydrase IX (CAIX) is a strictly membranous expressed metalloenzyme involved in cell adhesion, pH homeostasis, and cancer progression. The protein is specifically overexpressed in a wide variety of malignant tumors. This study was designed to assess the role of CAIX in primary vulvar cancer. One hundred forty-two well-characterized primary vulvar carcinomas were analyzed on a tissue microarray (TMA). Three tissue cores were sampled from each tumor. CAIX expression was determined by immunohistochemistry, using a four-step scoring system. To determine CAIX expression in benign vulvar tissue, we constructed a TMA with 120 samples of normal mucosa and non-neoplastic diseases. CAIX expression was found in 77/135 (57%) of all assessable vulvar cancer specimens and 48 (35.5%) exhibited a moderate or strong expression. CAIX expression in vulvar carcinomas was significantly stronger compared to non-neoplastic vulvar tissue (p < 0.001). High levels of CAIX expression were related to pT stage (p < 0.01), tumor size (p < 0.01), depth of invasion (p < 0.05), as well as inguinal lymph node metastases (p < 0.05). There was also a trend towards shorter recurrence-free patient survival in CAIX-positive compared to CAIX-negative vulvar cancers. CAIX staining results in different tissue cores from the same tumor were homogeneous, raising the possibility of a hypoxia-independent expression. In conclusion, CAIX is overexpressed in the majority of vulvar carcinomas with relationships to advanced tumor stages and development of lymph node metastases. Our data support the potential therapeutic benefit of newly developed targeting antibodies in advanced vulvar cancer.