S-phase fractions of colorectal carcinomas related to pathologic and clinical features

Abstract

The S-phase fractions (SPFs) of epithelial cells in 100 resected colorectal carcinomas were measured by in vitro exposure to tritiated thymidine and autoradiography. The frequency distribution of SPFs was gaussian with a median of 17.8 per hundred in 90 unirradiated carcinomas, whereas in ten carcinomas given radiation therapy preoperatively, it was positively skewed with a median of 6.9. Analysis of the unirradiated carcinomas showed no relationship between SPF and various clinical and morphologic features that included age, race, sex, site, size, Dukes' stage, histologic grade of the tumor, number of metastasis-bearing regional lymph nodes, presence of adenomas of the large bowel, survival or relapse-free survival of the patient, or SPF or adjacent normal colorectal crypts. The results show no evidence that colorectal carcinomas can be divided into kinetic subsets. The spatial orientation of labeled cells in autoradiographs indicated presence of a nonproliferative fraction of cells in many tumors that may modulate response to radiation therapy and chemotherapy.

p53 and PCNA expression in advanced colorectal cancer: Response to chemotherapy and long-term prognosis

“…These findings are in agreement with the results of Meyer and Prioleau (1981) and Faranda et al (1994), who utilized 3H-thymidine autoradiographic assay and flow-cytometry, respectively, to characterize the cell kinetics of very small series of chemotherapeutically treated advanced-colorectal-cancer patients. Also, in operable colorectal cancer, Neoptolemos et al (1995) reported that in younger patients (<70 years) a significantly worse prognosis was found for tumors with the lowest PCNA expression; finally, Johnston et al (1994), measuring tumor-cell kinetics by thymidylate-synthase expression, found that the benefit from adjuvant chemotherapy was evident only in fast proliferating tumors.…”

Implications of disaggregation procedures on biological representation of human solid tumours

“…In fact, as consistently described (Chavaudra, Richard &Malaise, 1979;Kerr, Robertson & Lamb, 1983) the scoringof labelled cells is performed not only in the highly labelled areas but along all the peripheral areas of many fragments picked up from different areas to overcome the intralesional variability peculiar to solid tumours. Again, a high potential proliferative activity (Meyer & Prioleau, 1981) and a prolonged volume doubling time, as reported for colorectal tumours (Welin e l al., 1963), are not necessarily contradictory results and could be explained by a high cell loss, as may occur in a tumour derived from a tissue characterized by a high exfoliation process, such as the colorectum.…”

Cell Kinetic Study of Human Carcinomas Using Bromodeoxyuridine

“…BrdU is a pyrimidine analogue of thymidine which is incorporated into DNA, and has been widely used as a radiosensitizer for cancer treatment; the method of immunohistochemistry by BrdU is also thought to be useful for studying cell proliferation patterns of human carcinomas. Several reports are available on the cell kinetics of human malignant tumours using [3H]thymidine autoradiography in uiuo (Hoffman & Joseph, 1967) and in uitro (Meyer & Prioleau, 1981 ;Ota & Drewinko, 1985). Because heterogeneity of the distribution of stained cells was observed in these tumours, it was suggested that investigation of DNA-synthesizing cells at the histological level was necessary to clarify the cell proliferation pattern of human tumours.…”