Clinicopathological significance of carbonic anhydrase 9, glucose transporter-1, Ki-67 and p53 expression in oral squamous cell carcinoma

Abstract

Abstract. carbonic anhydrase 9 (cA9) is a glycoprotein present on the surface of cell membranes. It is expressed in 90% of renal cancer cells, but not in normal kidney tissue. Immunotherapy targeting cA9 is underway, and our group has also conducted a clinical trial using cA9 as a cancer vaccine and confirmed the induction of cytotoxic T lymphocytes, with efficacy in some cases. Expression of CA9 antigen in oral cancer has not been reported in Japan, but our results indicate that immunotherapy targeting cA9 might be possible. We immunohistochemically observed the expression of antigens such as cA9, Ki-67, glucose transporter-1 (glUt-1) and p53 in 107 subjects with oral squamous cell carcinoma, and examined their correlation with clinicopathological parameters. Immunostaining analysis showed expression of cA9 in 98% of oral cancer subjects, and the survival rate was significantly lower in subjects with CA9 antigen expression in 50% or more cells (p<0.05). subjects with poorly differentiated, t4 and lymph node metastasis, or stage IV cancer with high CA9 expression (≥50%) had a worse outcome than those with low cA9 expression. Although glUt-1 expression was observed in 98% of subjects, similarly to cA9 expression, no significant correlation between its expression and the survival rate was seen. However, subjects with lymph node metastasis had significantly higher GLUT-1 expression, demonstrating that glUt-1 could be an indicator of lymph node metastasis. Ki-67 was expressed in 92% of subjects, but no correlation with outcome was observed. expression of p53 was noted in 78% of subjects, and it was found that many oral cancers have p53 genetic abnormalities, but no correlation between p53 and outcome was observed. It was confirmed that CA9 antigen is expressed in most oral cancer subjects, suggesting the possibility of immunotherapy targeting cA9 antigen in oral cancer.

Impacts of CA9 Gene Polymorphisms and Environmental Factors on Oral-Cancer Susceptibility and Clinicopathologic Characteristics in Taiwan

“…It was reported that high expression of CA9 was more frequent with lymph-node metastasis in several kinds of solid tumors including oral cancer [25], [36], [37]. In the present study, a significantly higher distribution frequency of lymph-node metastasis was exhibited in OSCC patients with at least 1 polymorphic G allele of CA9 +201 compared to those with the WT genotype (Table 6).…”

“…The aberrant expression of CA9 was observed in cancer cells themselves or tumor-associated stromal tissues in OSCC patients and correlated with a poor prognosis and nodal metastasis [17], [18], [25]. CA9 catalyzes the reversible hydration of carbon dioxide to carbonic acid.…”

Prognostic value of GLUT-1 expression in oral squamous cell carcinoma

“…Then 29 records were excluded because they lacked necessary information, did not study on OSCC patients, and were duplicate reports on the same patients or reviews. Finally, 13 studies [11–17,22–27] with 1301 subjects were included for meta-analysis. The flowchart of study selection was illustrated in Fig.…”

“…[9] A number of studies reported the direct link between high GLUT-1 levels and malignant conversion process. [11–14,16,17,22,30] The activity of GLUT-1 was regulated by oncogenes and growth factors. [11,31] Changes of GLUT-1 levels can be influenced by growth rate, oxygen supply, and malignant transformation.…”

The prognostic impact of a combined carbonic anhydrase IX and Ki67 signature in oral squamous cell carcinoma

“…It is well recognised that hypoxic tumours are generally associated with poor prognosis (Vaupel and Mayer, 2007; Jubb et al , 2010) and several groups have investigated the role of both hypoxia and proliferation in OSCC and other head and neck cancers (Ljungkvist et al , 2002; Hoogsteen et al , 2005; Kondo et al , 2011). Although a stromal CAIX and tumour Ki67 signature has not been previously explored, there is some support in the existing literature (Hoogsteen et al , 2005) for our combined hypoxia and proliferation-based prognostic signature providing a more biologically relevant definition of hypoxic tumours than sCAIX alone.…”