MOLECULAR CYTOGENETIC ANALYSIS OF CYTOKERATIN 20-LABELED CELLS IN PRIMARY TUMORS AND BONE-MARROW ASPIRATES FROM COLORECTAL-CARCINOMA PATIENTS

BACKGROUND. Low frequency epithelial cells in bone marrow from colorec tal carcinoma patients are associated with an increased risk of recurr ence and decreased survival. Current immunohistochemical approaches to detect epithelial cells in bone marrow aspirates rely on antibodies a gainst cytokeratin 18 (CK18). The predictive value of CK18-based detec tion strategies is limited by false-positives that occur in approximat ely 30% of cases. Cross-reactivity of anti-CK18 antibodies with nontum or cells may contribute to the false-positive rate. Cytokeratin 20 (CK 20) shows more restricted expression than CK18 and labels cells in col orectal tumors. METHODS, Immunofluorescence assays were used to quanti fy CK20-labeled cells in bone marrow aspirates and tumors from 18 Duke s stage C and D colorectal carcinoma patients to determine whether CK2 0 is useful in detecting micrometastases. Fluorescent in situ hybridiz ation was used to determine whether CK-labeled subpopulations carried genomic aberrations associated with colorectal carcinoma. RESULTS, CK2 0-labeled cells occurred at frequencies similar to 5 x 10(-5) in contr ol bone marrow aspirates from patients without colorectal carcinomas. Approximately 10(-4) CK20-labeled cells were present in 4 of 11 bone m arrow aspirates (45%) from patients with Dukes stage D colon carcinoma . The mean frequency (5 x 10(-5)) of CK20-labeled cells in Dukes stage C and D rectal carcinoma patients was statistically similar to contro l values. CONCLUSIONS. A subset of CK20-labeled cells in primary tumor s and hepatic metastases are aneusomic. CK20-labeled cells in bone mar row aspirates are cytogenetically normal. These data demonstrate that CK20 cells in solid tumors may be cytogenetically aberrant, but sugges t caution in the use of CE;20 to detect micrometastases in bone marrow aspirates. (C) 1997 American Cancer Society.