© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 18, 1363,
September 19, 2001
© 2001 Oxford University Press
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Studies of differential gene expression in metastatic cells with high versus low invasive activity may help identify genes associated with metastasis. Shih et al. (p. 1392) used microarray technology to select CRMP-1, a gene whose expression is inversely associated with the invasive activity of cancer cells. They found that, when the CRMP-1 gene was transfected into highly invasive cells and then overexpressed, transfected cells had lower invasive activity than untransfected cells. CRMP-1 protein was distributed uniformly in the cytoplasm in interphase cells, but in mitotic cells, CRMP-1 was associated with mitotic spindles and centrosomes. When CRMP-1 expression was assessed in lung cancer specimens, the authors observed that reduced expression was associated with specimens from patients with advanced disease, lymph node metastasis, early postoperative relapse, and a shorter survival. They concluded that CRMP-1 appears to be involved in cancer invasion and metastasis and may be an invasion suppressor gene.
In an accompanying editorial, Steeg (p. 1364) welcomes CRMP-1 as a possible lung cancer invasion suppressor gene and introduces the complex nature of the processes in which CRMP-1 may participate. She challenges cancer scientists to resolve these complexities.
Hip Replacements and Cancer
Some of the materials used to manufacture orthopedic implants and to hold them in place are known or suspected to cause cancer in animals or humans. It is unknown, however, whether patients who undergo hip replacement surgery are consequently at increased risk of cancer. Signorello et al. (p. 1405), in a prospective study of all patients who received hip implants in Sweden from 1965 through 1994, compared rates of cancer incidence at all anatomic sites in these patients with rates in the general population. They found that, overall, there was no excess of cancer in the patients who had hip replacements. However, among these patients, there was a somewhat increased incidence of prostate cancer and melanoma and a decreased incidence of stomach cancer, and longer follow-up revealed an excess of cases of multiple myeloma. The authors conclude that, although they could be due to chance or to bias, the observed elevations of specific types of cancer warrant further investigation.
Measurements of Childhood Brain Tumors
Although there is excellent concordance between the Response Evaluation Criteria in Solid Tumors (RECIST)—one-dimensional measurement—and World Health Organization criteria for measurement of extracranial solid tumors, the RECIST criteria have not been validated for brain tumors. End points, such as tumor response and time to tumor progression for assessing drug activity in brain tumors, are determined by measuring the change in tumor size relative to either a pretreatment or best-response scan by using magnetic resonance imaging. Warren et al. (p. 1401) compared one-dimensional, two-dimensional, and three-dimensional measurements of childhood brain tumors with clinical outcome. They found that concordance for detecting a partial response among all three methods was high, but less concordance was observed for classifying tumors in the minor response and progressive disease categories. They concluded that detection of partial responses was not influenced by the measurement method, but estimating time to disease progression may be method dependent for childhood brain tumors.
EGFR Signaling and the Invasive Phenotype
Many ovarian carcinomas have increased expression of the epidermal growth factor receptor (EGFR). Because EGFR signaling can regulate adhesion, invasion, and migration, Alper et al. (p. 1375) examined the relationship between EGFR and the invasive phenotype. The authors transfected NIH:OVCAR-8 ovarian cancer cells with an EGFR antisense expression vector to decrease EGFR expression. They found that these cells were morphologically distinct from vector control cells and had a selective decrease in adhesion to laminin-1 that was the result of a loss of expression of one of the components of the laminin-1 receptor, the 
6-integrin subunit. The authors also found that, compared with the vector control cells, both matrix metalloproteinase-9 activity and motility decreased in the antisense-transfected cells. The authors conclude that EGFR overexpression results in multiple phenotypic changes that enhance the invasive phenotype in ovarian cancer cells.
Allelic Variation in UGT1A7 and Orolaryngeal Cancer Risk
The enzyme UDP-glucuronosyltransferase 1A7 detoxifies the tobacco carcinogen benzo[a]pyrene (BaP). The gene that encodes it, UGT1A7, has four known alleles that encode isozymes that differ in their activities against BaP. However, it is not known whether allelic variation in UGT1A7 influences risk for cancer. Zheng et al. (p. 1411) measured UGT1A7 expression in normal tissue samples from patients with orolaryngeal cancer. The authors found that UGT1A7 messenger RNA was expressed at similar levels in all orolaryngeal tissues examined. The authors also found that individuals with any of the predicted low-activity UGT1A7 genotypes had an estimated 3.7-fold increased risk of orolaryngeal cancer compared with individuals with the wild-type UGT1A7 genotype. The authors found that this increase in risk was observed in smokers but not in nonsmokers, although the interaction between UGT1A7 genotype and smoking was not statistically significant. The authors conclude that genetic variations that reduce the activity of UGT1A7 may affect smoking-related orolaryngeal cancer risk.
Fluorescence Versus White-Light Bronchoscopy
The ability to detect preneoplastic bronchial lesions in high-risk individuals is of clinical relevance because of the limited number of methods for screening and early detection available. Although the conventional white-light bronchoscopy (WLB) procedure is commonly used to detect preneoplastic lesions, it has a low sensitivity. Laser-induced fluorescence endoscopy (LIFE), which detects tissue autofluorescence when the lung tissue is illuminated with fluorescent light, has been reported to have a greater sensitivity than WLB. To avoid some of the potential methodologic biases of the earlier comparison studies, Hirsch et al. (p. 1385) conducted a randomized trial whereby the order of the bronchoscopy procedures (WLB and LIFE) and the bronchoscopists who performed each procedure (each performed one procedure) were randomly assigned to each patient at high-risk for lung cancer. The authors found that LIFE was more sensitive but less specific than WLB.
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