Relationship between histologic features, DNA flow cytometry, and clinical behavior of squamous cell carcinomas of the larynx

Article Abstract:

Some cancers are associated with specific chromosome abnormalities. In other cancers, there is evidence that with the continued growth of the cancer, cells accumulate possessing abnormal numbers of chromosomes. Normally, somatic cells possess 23 pairs of chromosomes, a condition known as diploidy. Exactly double this chromosome complement is called tetraploidy, and cells in which a smattering of chromosomes are either duplicated or deleted are called aneuploid. There is considerable evidence that for many types of cancer, patients with diploid cancer cells enjoy a better prognosis than do patients whose cancers involve tetraploid or aneuploid cells. Traditionally, the chromosome complement of cells was directly observed through karyotyping. This slow, laborious, and expensive technique requires special skill and is not suitable for routine use. However, the advent of flow cytometry provides a quick and inexpensive method for estimating the ploidy of a set of tumor cells. By measuring the DNA content of fluorescently labelled cells one at a time, a profile of DNA can be generated. While the ploidy of a cell is not measured directly, it may be inferred from the resulting DNA histograms. Using this method, researchers examined the DNA content of 133 primary squamous cell carcinomas of the larynx. Fifty-seven were found to be diploid in DNA content. While it was found that high-grade undifferentiated cancers were more likely not to be diploid, ploidy was also found to provide independent prognostic information. When only low-grade cancers were considered, the four-year survival was 42 percent among those with diploid tumors and only 28 percent among those with aneuploid or tetraploid tumors. When only early stage cancers were considered, the four-year survival was 82 percent among those with diploid cancer and 49 percent among those with other chromosomal arrangements. The results confirm that in the case of squamous cell carcinoma of the larynx, ploidy as determined by flow cytometry may provide useful prognostic information. Furthermore, the prognostic value of ploidy may become significant early in the development of a particular case before other prognostic factors become available. (Consumer Summary produced by Reliance Medical Information, Inc.)

Methods, Squamous cell carcinoma, Laryngeal cancer

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Flow cytometric analysis of nuclear DNA content in advanced gastric cancer and its relationship with prognosis

Article Abstract:

The flow cytometer provides a method for analyzing the DNA content of cells on a cell-by-cell basis. In this way, it is possible to determine how many cells in a tumor have normal amounts of DNA and how many have abnormal amounts. Often, the abnormal amounts reflect an abnormal number of chromosomes, a condition called aneuploidy. In a number of different cancers, but by no means all, aneuploid cells in a cancer are associated with a poorer prognosis than tumors which contain predominantly normal diploid cells. The authors used flow cytometry to evaluate the DNA content of advanced stomach cancer in 270 patients. The study was conducted in Japan, where gastric cancer is proportionately more serious than in the United States. Aneuploid cells were identified in samples of 150 tumors, or 55.6 percent; statistical analysis revealed that the patients with aneuploid tumors had a worse outcome, on the average, than did the patients with diploid cells in their tumors. The five-year survival rate for patients with diploid tumors was 62.9 percent while the five-year survival of patients with aneuploid tumors was only 22.7 percent. The two most important predictors of the outcome of stomach cancer are the existence of cancerous spread to the peritoneal (abdominal) cavity and the presence of metastatic disease within the liver. Despite strong correlations between aneuploidy and peritoneal dissemination and liver metastases, cell aneuploidy was found to predict prognosis independently as well. Indeed, analysis of the various predictors revealed that the ploidy of the cancer cells was the third most significant predictor of outcome. The DNA index, which is a measure of the rate that cells are synthesizing DNA, and thus a measure of the rate of proliferation of the cells, is in general not as robust a predictor of cancer outcome as ploidy. However, the authors found that when only the patients with aneuploid tumors were considered, there was a strong association between DNA index and survival. In the aneuploid group, unusually high or unusually low rates of DNA synthesis were found to be associated with decreased median survival time. (Consumer Summary produced by Reliance Medical Information, Inc.)

Abnormalities, Cell proliferation, Stomach cancer

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A prospective evaluation of the effect of tumor cell DNA content on recurrence in colorectal cancer

Article Abstract:

Patients with early stage colorectal cancer have a better prognosis than patients with advanced metastatic disease. However, between the two extremes there are many patients for whom the prognosis is uncertain. One way in which a firmer prognosis might be established is by examining the DNA content of tumor cells using the automated flow cytometry technique. Previous research using archival tissue specimens has retrospectively compared case outcome with DNA content and found that abnormal DNA profiles are associated with a poor outcome. Researchers have now evaluated flow cytometry as a prognostic tool in a prospective study involving 320 colorectal cancer patients. The DNA profiles of the patients were determined, and each patient was then followed-up for a minimum of two years. No correlation was found between aneuploidy, or having an abnormal number of chromosomes in some tumor cells, and other potential prognostic factors such as patient age or tumor stage or grade. Of the 320 patients, 236 had surgery which was potentially curative. Among these patients, those with aneuploid tumors were twice as likely to have a local recurrence in the colon or rectum and three times more likely to develop distant metastatic disease than patients with diploid (with a normal number of chromosomes) tumors. However, this finding was not quite statistically significant when the entire group of patients was considered as a whole. Most of the prognostic influence of DNA ploidy was exerted in the patients with Stage B cancer. For patients with earlier or more advanced stages of colorectal cancer, DNA ploidy did not exert much influence on the case outcome. The authors suggest that DNA ploidy might be useful in determining which patients might benefit most from adjuvant chemotherapy in addition to their surgery. Also, studies of the effectiveness of treatment might benefit from analyzing data according to DNA ploidy as well as according to the more traditional stages and grades. (Consumer Summary produced by Reliance Medical Information, Inc.)

Colorectal cancer

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