Purpose: Minichromosome maintenance protein 2 (MCM2) is a component of the
prereplicative complex. It is essential for eukaryotic DNA replication and
is only expressed in proliferating cells. The prognostic utility of MCM2 co
mpared with Ki-67, another marker of proliferating cells, on survival of pa
tients with non-small-cell lung cancer (NSCLC) was studied.
Patients and Methods: We examined the immunohistochemical expression of MCM
2 and Ki-67 in primary pathologic tumor specimens from 221 NSCLC patients.
For each marker, the fraction of tumor cells with positive staining was ass
essed as a percentage and categorized into four groups: 0% to 24%, 25% to 4
9%,50% to 74%, and greater than or equal to 75%. MCM2 and Ki-67 immunoreact
ivities were compared with each other, and associations with pathologic and
clinical parameters predictive of survival were analyzed with the x(2) tes
t. Cox regression models were used to assess associations between MCM2 and
Ki-67 and survival while controlling for confounders.
Results: Independent variables significantly associated with survival were
tumor stage, performance status, and staining category. Patients with less
than 25% MCM2 immunoreactivity had a longer median survival time than patie
nts with greater than or equal to 25% MCM2 immunoreactivity (46 v31 months;
P = .039) and a lower relative risk (RR) of death (RR, 0.55, 95% confidenc
e interval, 0.34 to 0.88). There was no significant association between sur
vival and Ki-67 expression.
Conclusion: Immunostaining of tumor cells for MCM2 is an independent progno
stic parameter of survival for patients with NSCLC. Interpretable results c
an be obtained on more than 96% of paraffin-embedded specimens, and approxi
mately 35% will be in the favorable subgroup, with less than 25% positively
stained tumor cells. Whether MCM2 is predictive of response to therapy nee
ds to be studied.