Non-small cell lung cancer (NSCLC) is the leading cause of cancer morality
in men and women in the United States, and the overall long-term survial is
less than 15%. Pathologic stage I makes up 25-35% of NSCLC cases and has
a good prognosis. However, cancer relapse and death rate in this subset is
35 to 50% by 5 years. Chemotherapy is beneficial for the treatment of
several localized solid tumors after resection and may prove to be useful
in the treatment of patients with stage I NSCLC. Thr purpose of this
project is to define tissue and serum tumor markers in patients with stage
I NSCLC which predict for early cancer recurrence. Pathologic stage I
NSCLC was chosen for study to eliminate the significant influence of
positive lymph nodes and distant metastases on survival.
Immunohistochemical staining will identify potential tissue tumor markers
and radioimmunoassay (RIA) or enzyme-link immunosorbent assay (ELISA) will
identify potential serum tumor markers.
Specific aim #1 will examine a set of twelve tissue tumor markers in a
retrospective cohort of 275 stage I NSCLC patients. Markers are
categorized by hypothetical method of action: molecular genetic markers
(Kras, erbB-1, erbB-2, rb, p53, bcl-2), markers of metastatic propensity
(angiogenesis factor viii), proliferation markers (K1-67) and markers of
cellular differentiation (Blood group A, H/LeV/LeB, NCAM, CD44). Results
will be used to develop a prediction rule for recurrence in stage I NSCLC
using Cox proportional hazards regression analysis and an artificial neural
Specific aim #2 will examine a set of eight serum tumor markers in a
retrospective cohort of 250 patients with stage I to IV NSCLC. These
markers are categorized as molecular genetic markers (anti-p53), markers of
metastatic propensity (angiogenesis bFGF), somatamedins (growth factor IGF-
1) and markers of cellular differentiation (CEA, CA-125, CA 15-3, CYFRA21-
1, CD44). The purpose of this aim is to identify any correlations between
titers of serum markers and tumor histology, stage or mass. One hundred
patients in this cohort had a second serum collection after tumor
resection. This subgroup of serum will allow analyses of titters before
and after cyto-reduction. Significant correlates with tumor stage and mass
will be evaluated in a prospective cohort of patients with stage I NSCLC.
In specific aim #3, paraffin-embedded and fresh-frozen tumor tissue will be
collected from a prospective cohort of 330 patients with stage I NSCLC to
validate the prediction rule developed in specific aim #1. In these same
patients, serial serum specimens will be collected for a minimum of 2.0
years after resection (specific aim #4). The significant markers
identified in specific aim #2 will be analyzed in this cohort to describe
correlations with tumor recurrence. Tissue and serum markers identified by
the model can be used to select high risk patients for a prospective,
multi-institutional chemotherapy trial for stage I NSCLC.
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