The use of biomarkers to assess cancer risk is based on the model of cancer as a multistep process; such markers are assumed to reflect an early stage in this process. A valid biomarker of risk must therefore show differential expression in normal and high-risk subjects, as well as quantitative correlation with the stage of carcinogenesis. It should also be easy to detect in small tissue specimens and responsive to modulation by chemopreventive agents. Cell proliferation is one of the most widely investigated markers of cancer risk. Case-control studies have shown that epithelial cell proliferation parameters, assessed in rectal mucosal biopsies by means of in vitro autoradiographic or immunohistochemical techniques, can discriminate between populations with normal and high risks for colon cancer. However, we recently reviewed rectal biopsies from 152 subjects (43 controls, 84 with adenomas, 25 resected for colon cancer) processed for in vitro 3H-thymidine autoradiography, and attempted to correlate various proliferative parameters with clinical and pathological variables by means of multiple regression analysis. Elevations of total crypt labeling indices (LIs), particularly upper crypt LIs, were significantly associated with the presence of adenomatous polyps, although subsequent linear discriminant analysis revealed that the accuracy of LIS in discriminating between polyp patients and controls was actually quite low. However, we have also found that upper crypt LIs are reliable predictors of adenomatous polyp recurrence. Repeated evaluations of rectal proliferative indices over a 2-year post-polypectomy follow-up of 40 patients with colonic adenomas revealed substantial stability. We have also shown that, although circadian variation occurs, it is confined to the normal proliferative zone in the lower crypt, with upper crypt proliferation remaining quite stable. These proliferative indices have been shown to respond to chemopreventive agents (dietary and chemical), and we have recently shown that the improvements obtained with ω-3 fatty-acid supplementation persist during long-term treatment. Although definitive validation of the rectal epithelial cell proliferation biomarker has not yet been achieved, recent prospective studies have shown parallel effects by putative chemopreventive agents on cell proliferation and precursor lesions of colorectal cancer.

Reliability of rectal epithelial kinetic patterns as an intermediate biomarker of colon cancer / Anti, M.; Marra, G.; Percesepe, A.; Armelao, F.; Gasbarrini, G.. - In: JOURNAL OF CELLULAR BIOCHEMISTRY. - ISSN 0730-2312. - 56:SUPPL. 19(1994), pp. 68-75.

Reliability of rectal epithelial kinetic patterns as an intermediate biomarker of colon cancer

Percesepe, A.;
1994

Abstract

The use of biomarkers to assess cancer risk is based on the model of cancer as a multistep process; such markers are assumed to reflect an early stage in this process. A valid biomarker of risk must therefore show differential expression in normal and high-risk subjects, as well as quantitative correlation with the stage of carcinogenesis. It should also be easy to detect in small tissue specimens and responsive to modulation by chemopreventive agents. Cell proliferation is one of the most widely investigated markers of cancer risk. Case-control studies have shown that epithelial cell proliferation parameters, assessed in rectal mucosal biopsies by means of in vitro autoradiographic or immunohistochemical techniques, can discriminate between populations with normal and high risks for colon cancer. However, we recently reviewed rectal biopsies from 152 subjects (43 controls, 84 with adenomas, 25 resected for colon cancer) processed for in vitro 3H-thymidine autoradiography, and attempted to correlate various proliferative parameters with clinical and pathological variables by means of multiple regression analysis. Elevations of total crypt labeling indices (LIs), particularly upper crypt LIs, were significantly associated with the presence of adenomatous polyps, although subsequent linear discriminant analysis revealed that the accuracy of LIS in discriminating between polyp patients and controls was actually quite low. However, we have also found that upper crypt LIs are reliable predictors of adenomatous polyp recurrence. Repeated evaluations of rectal proliferative indices over a 2-year post-polypectomy follow-up of 40 patients with colonic adenomas revealed substantial stability. We have also shown that, although circadian variation occurs, it is confined to the normal proliferative zone in the lower crypt, with upper crypt proliferation remaining quite stable. These proliferative indices have been shown to respond to chemopreventive agents (dietary and chemical), and we have recently shown that the improvements obtained with ω-3 fatty-acid supplementation persist during long-term treatment. Although definitive validation of the rectal epithelial cell proliferation biomarker has not yet been achieved, recent prospective studies have shown parallel effects by putative chemopreventive agents on cell proliferation and precursor lesions of colorectal cancer.
Reliability of rectal epithelial kinetic patterns as an intermediate biomarker of colon cancer / Anti, M.; Marra, G.; Percesepe, A.; Armelao, F.; Gasbarrini, G.. - In: JOURNAL OF CELLULAR BIOCHEMISTRY. - ISSN 0730-2312. - 56:SUPPL. 19(1994), pp. 68-75.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2868698
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