| Big Picture: |
Annexin I is a binding protein that serves many functions in the
body. Aberrantly high and low levels of this protein have been associated
with different types of cancer. Evidence of a loss of annexin I protein
in malignant as compared to normal esophageal mucosa suggests that
reduced levels of this protein may be linked to the development of
esophageal squamous cell cancer. To date, studies on annexin I have
examined only protein level changes in cancer, but not the mechanisms
that may be responsible for such changes. |
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| Focus: |
This study attempts to elucidate potential mechanisms underlying
the reported loss of annexin I in esophageal squamous cell cancer
by analyzing allelic loss, DNA mutations, mRNA expression and protein
levels of the annexin I gene in esophageal tumors. This may be
the first published study of annexin I in which mRNA expression
levels are quantified.
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| Findings: |
The investigators found frequent allelic loss of annexin I but
almost no mutations in esophageal tumors. They report that while
46 of 56 (82 percent) of esophageal squamous cell cancer patients
showed loss of an allele, somatic mutation of annexin I was found
in only one case. They also confirmed decreased annexin I protein
levels in esophageal cancer, consistent with reduced mRNA expression.
The loss of protein appeared to be related to tumor grade, with protein
levels reduced in 79 percent of poorly differentiated vs. five percent
of well-differentiated tumor samples. |
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| Conclusions: |
These results indicate that the reduction in annexin 1 protein
levels in esophageal squamous cell cancer is not caused by a “two-hit” combination
of allelic loss and somatic mutation. Nevertheless, reduced mRNA
and protein levels are associated with this type of cancer. |
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| Clinical Relevance: |
These data strongly suggest that the loss of annexin I mRNA expression
in squamous esophageal cancer is unrelated to genomic mutations or
epigenetic events and most likely explained by altered transcription.
Furthermore, the high prevalence of protein loss indicates that annexin
I is a strong candidate for inclusion in a panel of early detection
markers for this type of cancer. |
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| Next Steps: |
Future testing of protein expression with larger numbers of samples,
including biopsies with dysplastic or CIS lesions, should shed additional
light on the role of annexin I in the development of esophageal squamous
cell carcinoma. |
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| Study Team: |
Cancer Prevention Researchers, Center for Cancer Research, National
Cancer Institute
Clinical Researchers, Cancer Institute and Hospital, Chinese Academy of Medical
Sciences, Beijing and Shanxi Cancer Hospital, Taiyuan, Shanxi, People’s
Republic of China
Genetic Epidemiologist, Division of Cancer Epidemiology and Genetics, National
Cancer Institute
Pathologist, Center for Cancer Research, National Cancer Institute
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| Citation: |
Hu, N., Flaig, M.J., Su, H., Shou, J., Roth, M.J., Li, W., Wang,
C., Goldstein, A.M., Li, G., Emmert-Buck, M.R., and Taylor, P.R. “Comprehensive
characterization of annexin I alterations in esophageal squamous
cell carcinoma,” Clinical Cancer Research; Vol. 10, Sept. 15,
2004. |
