© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 5, 317,
March 6, 2002
© 2002 Oxford University Press
IN THIS ISSUE |
Neuroblastoma detected in screening programs frequently undergoes spontaneous regression during its natural course. Kitanaka et al. (p. 358) examined the mechanisms of spontaneous regression of neuroblastoma, focusing on the role of Ras as a favorable prognostic marker. They studied tumors from patients detected through a mass-screening program and from clinically detected, advanced-stage patients older than 1 year of age. They evaluated the tumor tissues for cell degeneration, expression of the Ras gene, and indicators of apoptosis. They found that Ras expression was increased in areas of autophagic degeneration that lacked features of apoptosis, e.g., nuclear condensation, DNA fragmentation, and caspase-3 activation. More such areas were seen in tumors from patients detected by mass-screening than in tumors from advanced-stage patients detected clinically. The neuroblastoma cells transfected in vitro with the H-Ras gene also showed similar cell degeneration characteristics. The authors conclude that Ras-mediated nonapoptotic tumor cell death may play a key role in spontaneous regression of neuroblastoma.
In an editorial, Reynolds (p. 319) points out that more work is needed to determine whether apoptosis, non-apoptotic programmed cell death, or both predominate in spontaneous regression of neuroblastoma and whether the predominant mechanism varies from tumor to tumor. He states that the findings of Kitanaka et al. provide evidence that "spontaneous" programmed cell death may occur via a caspase-independent, non-apoptotic mechanism.
Accuracy of Mammography Interpretation
Countries with centralized, high-volume mammography screening programs, such as the United Kingdom, emphasize high specificity and high sensitivity. In contrast, the United States does not have centralized high-volume screening programs, emphasizes high sensitivity, and has lower average rates of biopsy. With the use of the PERFORMS 2 test, the U.K.’s National Health Service Breast Screening Programme teaching and assessment tool, Esserman et al. (p. 369) evaluated 60 U.S. radiologists to determine whether high sensitivity can be achieved in the context of high specificity and whether the number of mammograms read per radiologist (reader volume) drives both the sensitivity and specificity. The authors found that there was a direct, positive relationship between the reader volume and the average sensitivity at a specificity of 90%, with high-volume readers having the highest average sensitivity and low-volume readers having the lowest. The authors conclude that reader volume is an important determinant of mammogram sensitivity and specificity and that high sensitivity can be achieved with high specificity in high-volume centers.
In an accompanying editorial, Elmore and Carney (p. 321) discuss the complexities associated with making comparisons between U.S. and U.K. radiologists’ interpretive practices in routine mammography, including fiscal and medico-legal issues. They also underscore the limitations of using a testing situation for determining routine mammography interpretations in the community setting.
Race, Ethnicity, and Cancer Treatment
To evaluate racial/ethnic disparities in the receipt of cancer treatment, Shavers and Brown (p. 334) reviewed the published literature on the access/use of specific cancer treatment procedures, trends in patterns of use, or survival studies. They found evidence of racial disparities in receipt of definitive primary therapy, conservative therapy, and adjuvant therapy that could not be completely explained by racial/ethnic variation in clinically relevant factors. The treatment differences identified were associated with various adverse health outcomes for these groups. They suggest that reducing the influence of nonclinical factors on the receipt of cancer treatment may reduce the racial/ethnic disparities in health. They recommend that new data resources and improved study methodology be developed to identify and quantify the full spectrum of nonclinical factors contributing to this problem and that new strategies be developed to deliver appropriate cancer care to all patients.
Gastrin-Releasing Peptide and Squamous Cell Carcinoma
Gastrin-releasing peptide (GRP) is a potent mitogen involved in tobacco-mediated lung injury and lung cancer. Effects of GRP are mediated through the GRP receptor (GRPR). Lango et al. (p. 375) studied the expression of these proteins and their involvement in squamous cell carcinoma of the head and neck (SCCHN). They found that both tumor and normal mucosa from SCCHN patients expressed higher levels of GRPR than normal mucosa from non-cancer patients. They also found that GRPR levels in the tumor and adjacent normal mucosa were correlated, suggesting that increased GRPR expression is an early event in the development of SCCHN. GRP stimulated the proliferation of SCCHN cells, and neutralizing GRP antibodies inhibited this proliferation. They conclude that GRP and GRPR appear to participate in an autocrine regulatory pathway in SCCHN, which might be an effective target for therapies for SCCHN.
Receptor Methylation and Prostate Cancer
Prostate cancer is initially steroid hormone dependent, and receptors for estrogen, androgen, and progesterone have been identified in prostate cancers. Sasaki et al. (p. 384) investigated whether the gene promoters for three estrogen receptor-
isoforms, estrogen receptor-
, androgen receptor, and two progesterone receptor isoforms were methylated and thus inactivated in cancerous prostate tissues and cells. They found that certain steroid hormone receptor genes were inactivated by promoter methylation in prostate cancer cell lines. When these cell lines were treated with a demethylating agent, all unexpressed receptor genes were expressed, confirming that methylation was responsible. When normal and cancer prostate tissues were compared, most estrogen receptor promoters were unmethylated in all normal tissues but methylated in most cancer tissues, and the androgen receptor promoter was unmethylated in all normal tissues and almost all cancer tissues. Progesterone receptor promoters were unmethylated in all tissues. Thus, the authors conclude that certain steroid hormone receptor genes appear to be inactivated by methylation in prostate cancer.
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