title: Topoisomerase I protein expression in primary colorectal cancer and lymph node metastases.
abstract: Topoisomerase I (topo I) is an important target for the treatment of malignant disease, especially colorectal cancer. Because there is little information on the expression of topo I in colorectal tumors, this study evaluated and characterized topo I protein expression in primary colorectal cancer and lymph node metastases and studied the association between topo I protein expression and clinicopathologic data, p53 status, and proliferating cell nuclear antigen (PCNA) status. Immunohistochemistry assay was performed for topo I protein expression in 249 primary human colorectal cancer and 42 paired lymph node metastasis samples. Topo I expression was described as the percentage of cells staining positive for topo I, along with the intensity and localization of the staining. Clinicopathologic data (sex, age, Dukes' stage, differentiation grade, survival status), p53 status, and PCNA status were statistically analyzed for association with topo I protein expression. Topo I expression in paired primary lymph node metastases were studied for concordance. Topo I protein expression was detected in 127 (51%) samples, including 24.4% with >50% positive tumor cells. The majority had nuclear (70.1%) or nuclear and cytoplasmic staining (17.3%). A higher percentage of cells expressing topo I in primary colorectal cancer was significantly associated with advanced age (P =.040). Patients with rectal cancer had greater topo I expression than those with colon tumors (P =.029). No significant correlation was found between topo I protein expression and sex, Dukes' stage, differentiation grade, survival status, p53 status, and PCNA status. Concordance in topo I staining between primary and lymph node metastases was observed in 33 of 42 cases (P =.029). This suggests that the activity of topo I inhibitors will not differ across various tumor stages, pathology, and patient gender. p53 and PCNA status do not appear to influence topo I expression, and topo I has no apparent association with the acquisition of a metastatic phenotype. Topo I expression now needs to be evaluated in patients undergoing topo I-inhibitor therapy, to better define the role of this protein as a predictive marker.
authors.affiliation: Department of Medicine & Therapeutics and Pathology, University of Aberdeen Institute of Medical Sciences, Aberdeen, Scotland, UK.
authors.forename: Attasit
authors.initials: A
authors.lastname: Boonsong
authors.forename: Stephanie
authors.initials: S
authors.lastname: Curran
authors.forename: Judith A
authors.initials: JA
authors.lastname: McKay
authors.forename: James
authors.initials: J
authors.lastname: Cassidy
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Murray
authors.forename: Howard L
authors.initials: HL
authors.lastname: McLeod
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002452:Cell Count; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000201:enzymology* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D004264:DNA Topoisomerases, Type I