Use of neuroendocrine markers, p53, and HER2 to predict response to chemotherapy in patients with stage III non-small cell lung cancer: a Cancer and Leukemia Group B study

Several studies have suggested that non-small Cell lung cancer (NSCLC) pati ents whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of p53 and HER2 may conf er relative chemotherapy resistance and shortened survival. The Cancer and Leukemia Group B performed a series of studies involving sequential chemoth erapy followed by radiation for patients with unresectable stage Ill NSCLC. The objectives of this study were to analyze pathological specimens using immunohistochemistry for NE markers, p53 and HER2 to determine if there was a correlation between marker expression and response or survival. Of 160 e ligible patients, 28 (18%) were not evaluable because of inadequate materia l. The percentage of specimens positive for markers was as follows: neuron- specific enolase 38%, Leu-7 2%, chromogranin A 0%, synaptophysin 5%, greate r than or equal to 2 + NE markers 3%, p53 61%, and HER2 65%. There was no s tatistically significant correlation between any individual marker and resp onse to induction chemotherapy or response to combined chemotherapy/radiati on except for synaptophysin. Six of 6 (100%) synaptophysin positive tumors responded by the completion of all therapy compared with 69/125 (55%) synap tophysin negative tumors (P = 0.04). None of the individual markers had a s ignificant effect on survival in univariate analysis. Neuron-specific enola se was marginally significant in multivariate analysis (P = 0.08). In concl usion, this study did not demonstrate that expression of NE markers, p53 an d HER2 were predictive of response to chemotherapy, combined chemotherapy/r adiation or for survival in this group of patients with stage III NSCLC. Fu ture studies must employ either different markers or be performed on more a dequate surgical specimens. (C) 2001 Elsevier Science Ireland Ltd. All righ ts reserved.