Significance of Clq-binding Macromolecules within the Head and Neck Cancer Patient

Elevated levels of macromolecules, within the peripheral blood of head and neck cancer patients, capable of binding the first component of complement (ClqBM) in vitro have prognostic implication. Namely, elevated levels of ClqBM have been associated with nonresponse to induction chemotherapy. In this investigation, a series of in vitro studies regarding the biological properties of ClqBM were combined with a longitudinal analysis of 112 previously untreated head and neck cancer patients. Our purpose was to shed light on the biological significance of this circulating macromolecule, a substance composed, in part, of IgG and IgM. A potential confounding influence of ClqBM with induction chemotherapy, which could contribute to observed prognostic findings, was negated by two in vitro observations: the macromolecule failed both to bind the chemotherapeutic agents cisplatin, bleomycin, and 5-fluo-rouracil and to impede the cytotoxic effect of these same drugs on a cultured human head and neck cancer cell line. The clinical relevance of ClqBM was reinforced by the observation that elevated levels predicted a high probability of death with disease (P = 0.005 by Cox's proportional hazards model). The prognostic implication was independent of the use of induction chemotherapy, i.e., patients with high ClqBM levels treated with multimodality therapy not composed of anticancer drugs did equally poorly. Thus, the prognostic significance of ClqBM in patients undergoing induction chemotherapy appears independent of drug effect and appears reflective of tumors that are more rapidly progressive and potentially less responsive to therapeutic intervention, including combinations of surgery, radiation, and/or chemotherapy.