Expression of cell cycle control proteins in primary colorectal tumors does not always predict expression in lymph node metastases

Analysis of tumor markers focuses on expression in primary tumors with the assumption that this is representative of metastatic tumor, against which t reatment is targeted. Few studies have compared the expression of such mark ers in primary and secondary tumors, In this study, several key genes invol ved in cell cycle regulation were investigated in colorectal tumors and cor responding lymph node metastases, The cell cycle regulators p53, cyclin D1, p21, p27, retinoblastoma protein (Rb), and proliferating cell nuclear anti gen (PCNA) were examined in a series of 42 paired samples of primary colore ctal and secondary lymph node tumors by immunohistochemistry. Expression of p53, p27, and Rb was similar in virtually all paired samples (p53, 38 of 4 2; p27, 39 of 42; Rb, 40 of 42), indicating that the pattern of these prote ins in colorectal tumors may be used to predict that in lymph node tumors. It also suggests a lack of direct involvement in the metastatic process. A lower concordance for p21 and cyclin D1 staining was observed between prima ry and secondary tumors (p21, 19 of 42; cyclin D1, 22 of 42), p21 expressio n was more often observed in primary colorectal cancers, whereas cyclin D1 expression was more frequently seen in lymph node metastases, in keeping wi th the contrasting roles of these proteins as a cell cycle inhibitor (p21) and activator (cyclin D1). The PCNA-labeling index was found to vary consid erably in a number of cases, thus limiting the ability to predict expressio n of this protein in lymph node metastases from the primary tumor. In addit ion, PCNA-labeling indices between paired samples were neither consistently higher nor lower, suggesting that the proliferative capacity of tumor cell s is not directly related to their ability to metastasize.