Carbonic Anhydrase IX as a Marker for Poor Prognosis in Soft Tissue Sarcoma

Måseide, Kårstein; Kandel, Rita A.; Bell, Robert S.; Catton, Charles; O’Sullivan, Brian; Wunder, Jay S.; Pintilie, Melania; Hedley, David W.; Hill, Richard P.

doi:10.1158/1078-0432.ccr-03-0541

Cited by 77 publications

(69 citation statements)

References 28 publications

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“…There are numerous reports showing that CA IX acts not only as a marker for particular tumors, but its presence also correlates to prognosis in several tumor categories, such as brain tumors, sarcomas, and renal, lung, rectal, bladder, oral, breast, and cervical carcinomas [7,[27][28][29][30][31][32][33][34]. Although studies on CA II and CA XII have been mainly focused on normal tissues, there are a few previous reports, showing their presence in cancer cells and especially in brain tumors where they have shown significant association with prognosis [6,7,25].…”

Section: Discussionmentioning

confidence: 99%

Carbonic anhydrase VII–a potential prognostic marker in gliomas

Bootorabi¹,

Haapasalo²,

Smith³

et al. 2011

Health

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Carbonic anhydrase VII (CA VII) is a cytosolic enzyme expressed in several organs, including the human brain, but it has not been investigated earlier in any tumors. We designed the present study to evaluate CA VII expression in a cohort of human diffuse astrocytomas, mixed oligoastrocytomas and oligodendrogliomas. CA VII immunostaining was correlated to clinicopathologic findings, survival data, and expression of other molecular factors, including Ki-67, p53 protein and epidermal growth factor receptor. CA VII-positive staining was observed in 94% of astrocytomas and 85% of oligodendrogliomas. In the tumor specimens, strong positive areas were often located in close proximity to necrosis. The CA VII immunoreactivity showed positive correlation with tumor malignancy grades of astrocytomas (p = 0.02, chi-square test). In all tumor categories, CA VII-positive staining was often seen in the endothelial cells of neovessels in addition to the tumor cells. CA VII intensity showed no significant association with p53 nor did it correlate with the amplification of epidermal growth factor receptor (analyzed only in astrocytomas) or cell proliferation. Our present results show that CA VII may act as a useful biomarker in histopathologic diagnostics of gliomas. The high expression of CA VII in the tumor cells and endothelium suggests important roles for the enzyme in tumor metabolism. The results also led us to conclude that CA VII might serve as a marker of poor prognosis in diffuse astrocytomas.

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Section: Discussionmentioning

confidence: 99%

Carbonic anhydrase VII–a potential prognostic marker in gliomas

Bootorabi¹,

Haapasalo²,

Smith³

et al. 2011

Health

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“…this is a cancer-associated antigen recognized by antibodies, produced by cervical cancer or renal cell carcinoma cells, and is expressed in normal tissues of gastrointestinal tract membranes, bile ducts (7) and skin (unpublished data). recently, many research groups have reported its expression not only in renal cell carcinoma and cervical cancer, but also in bladder cancer, non-small cell lung cancer, breast cancer, head and neck cancer, esophageal cancer, stomach cancer, large intestine cancer, bile duct cancer, sarcoma and chronic myeloid leukemia (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). yoshikawa et al prepared mousederived renal cell carcinoma cells expressing human cA9 antigen.…”

Section: Introductionmentioning

confidence: 99%

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

Kondo

Yoshikawa

Omura³

et al. 2011

Oncol Rep

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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.

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“…32 CA-9 is a well-known marker of tumor hypoxia identifiable by its intense surface membrane staining, commonly seen in hypoxic tissue. [33][34][35] Recently, Iakovlev et al 36 showed that CA-9 labeling was correlated with direct pO 2 measurements in cervical carcinoma and that there was significant intratumoral heterogeneity. Our study further supports CA-9 as a suitable marker for identifying hypoxia and presents findings showing upregulated expression of a series of metastasis-related genes in sorted CA-9-positive (hypoxic) cells.…”

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Increased expression of metastasis-related genes in hypoxic cells sorted from cervical and lymph nodal xenograft tumors

Chaudary

Hill

2009

Laboratory Investigation

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Solid tumors contain regions of poor oxygenation that relate to the abnormal vascular network. Clinical investigations in cervical carcinoma have shown that positive lymph node status in patients with cervical carcinoma correlates with hypoxia. Earlier, in an orthotopic cervical cancer model, we had shown that exposure to acute hypoxia enhances lymph node metastasis. This study describes a technique for sorting hypoxic cells directly from the cervical xenograft model and reports the expression of 'metastasis-related' genes in hypoxic cells from xenografted cervix and lymph node tumors. Tumor cells were sorted on the basis of DsRed fluorescence and the sub-population of hypoxic cells was sorted on the basis of carbonic anhydrase-9 (CA-9) expression. Quantitative RT-PCR was conducted to measure changes in gene expression in the hypoxic cells sorted from primary cervix tumors and lymph node metastases. Immunohistochemistry was used to track changes in protein expression in sections of the same tumors. Metastasis-related genes, CXCR4, uPAR, VEGFC, Hdm2, and OPN, were observed to be upregulated at gene and protein levels in the primary tumors and nodal metastasis from the orthotopic transplants. In particular, the hypoxic cells sorted from orthotopically transplanted cervix tumors and their lymph node metastases from mice exposed to cyclic (intermittent) hypoxia showed higher levels of expression of these genes. These results are consistent with the hypothesis that these genes may be involved in regulating lymph node metastasis in cervical cancers under hypoxic conditions and provide support to the concept cyclic hypoxia that plays an important role in this process. Our methodological study emphasizes the technique of cell sorting to identify hypoxic cells using CA-9, which may aid in improving prognostic capabilities and in designing rational therapeutic strategies by focusing on hypoxia-specific gene expression profiles of patients. The technique can be applied to identify other potential 'hypoxia-related' genes of interest for tumor growth and metastasis.

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Carbonic Anhydrase IX as a Marker for Poor Prognosis in Soft Tissue Sarcoma

Cited by 77 publications

References 28 publications

Carbonic anhydrase VII–a potential prognostic marker in gliomas

Carbonic anhydrase VII–a potential prognostic marker in gliomas

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

Increased expression of metastasis-related genes in hypoxic cells sorted from cervical and lymph nodal xenograft tumors

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