Prognostic value of intratumoral carbonic anhydrase IX expression in testicular germ cell tumors

Abstract

Testicular germ cell tumors (TGCTs) represent a highly curable malignancy, however a small proportion of patients fails to be cured with cisplatin-based chemotherapy. Carbonic anhydrase IX (CA IX) is upregulated by hypoxia in several cancer types and correlates with a poor prognosis. The present translational study evaluated expression and prognostic value of CA IX in TGCTs. Surgical specimens from 228 patients with TGCTs were processed by the tissue microarray method and subjected to immunohistochemistry with the M75 monoclonal antibody. CA IX expression was evaluated in tumors vs. adjacent normal testicular tissues and correlated with clinicopathological characteristics and clinical outcome. CA IX expression was detected in 62 (30.2%) of TGCTs compared to 0 (0%) of normal tissue adjacent to testicular tumor (P<0.001). The highest frequency of the CA IX expression was detected in teratoma (39.0%), followed by seminoma (22.7%), yolk sac tumor (22.2%), embryonal carcinoma (11.9%) and choriocarcinoma (7.7%). None of germ cell neoplasias in situ (GCNIS) exhibited CA IX expression. Patients without the CA IX tumor expression showed significantly better progression-free survival, but not overall survival, compared to patients with the CA IX expression [hazard ratio (HR), 0.57; 95% CI, 0.32–1.02; P=0.037 and HR, 0.58; 95% CI, 0.29–1.16; P=0.088, respectively]. There was no significant correlation between the CA IX expression and clinicopathological variables. The intratumoral CA IX expression can serve as a prognostic marker in the TGCT patients. These results suggest that activation of the hypoxia-induced pathways may be important in the treatment failure in TGCTs patients.

Transcriptome analysis of human colorectal cancer biopsies reveals extensive expression correlations among genes related to cell proliferation, lipid metabolism, immune response and collagen catabolism

“…In contrast to the above carbonic anhydrase genes which were sharply downregulated in tumors, carbonic anhydrase 9 ( CA9 ), was overexpressed with a 47 fold expression increase in tumor samples. Upregulation of this CA gene is associated with poor prognosis [ 31 ].…”

Inhibition of carbonic anhydrase IX targets primary tumors, metastases, and cancer stem cells: Three for the price of one

“…Finally, a relationship between CA IX overexpression and cancer stem cells has also been evidenced . It is also worth noting that in many tumors high levels of CA IX have been associated with advanced stage or high grade of tumor and with a poor prognosis . In contrast, in renal clear cell carcinoma high levels of CA IX have been found to be associated with an overall good prognosis …”

“…50,72 It is also worth noting that in many tumors high levels of CA IX have been associated with advanced stage or high grade of tumor and with a poor prognosis. 50,[73][74][75] In contrast, in renal clear cell carcinoma high levels of CA IX have been found to be associated with an overall good prognosis. 49 With the exception of renal clear cell carcinoma, the expression of CA IX in tumors is almost always induced by hypoxia through the activation of the transcriptional complex HIF-1.…”

Emerging Prognostic Biomarkers in Testicular Germ Cell Tumors: Looking Beyond Established Practice

“…Levels of this marker of hypoxia and aggressive tumor behavior correlated in plasma and in tumor tissue. High expression in tumor was associated with shorter PFS; however, the clinically more useful utility of plasmatic assessment failed to be prognostic in GCT ( 46 , 47 ). The hepatocyte growth factor (HGF) and its receptor c-MET were investigated by immunohistochemistry in tumors and in cell-line culture.…”

“…Kalavska et al published two studies examining the prognostic value of carbonic anhydrase nine assessed from plasma and from tumor tissue ( 46 , 47 ). Levels of this marker of hypoxia and aggressive tumor behavior correlated in plasma and in tumor tissue.…”