PROGNOSTIC IMPORTANCE OF P27KIP1 EXPRESSION IN PATIENTS WITH NON-SMALL CELL LUNG CANCER

Introduction: Tumor node metastasis (TNM) staging and histological grading are acceptable classification systems for lung cancer (LC), but not
satisfactory to predict prognosis. p27Kip1 (p27) plays an important role in
cancer cell cycle regulation by inhibiting cyclin–CDK complex activity in
the nucleus. Recent evidence however, suggests that under certain conditions, p27 may function as an oncogene rather than a tumor suppressor gene.
Although most studies in LC patients indicated that loss of p27 protein
expression diminishes chance of survival, some investigators reported opposite findings. We assumed that this discrepancy could be attributed to the
inclusion of different groups of patients, lack of stratification by histological
grade, or non-standardized methodology.
Patients and methods: Ninety-two patients of all stages with previously
untreated non-small cell lung cancer (NSCLC) were included. Tumors
diagnosed as adenocarcinoma were evaluated for grade. The IHC localization of p27 was scored through a semiquantitative method. IHC studies were
also performed for p53, and Pirh2. The association between p27 H-Score
values and time-to-progression (TTP) and overall survival (OS) was analyzed with population-averaged, panel-data models by using generalized
estimation equations (GEE). TTP and OS time were analyzed with Cox
proportional hazards regression models.
Results: The mead H-Score value for p27 was equal to 91.2 83.7. The
relationship between p27 H-Score to TTP or OS time was polynomial for
both. Short TTP in patients with metastasis or whose tumors progressed
during the eight-month period after diagnosis was statistically associated
with overexpression of Pirh2 (P 0.001). In patients whose tumors progressed later, long TTP was associated with LC of the non-adenocarcinoma
type (P 0.027), p27 H-Score (P 0.032), and well-differentiated adenocarcinoma (P 0.047). None of the parameters was found to correlate with
OS time.
Conclusions: The interpretation of p27 H-Score has to be collaborated with
other clinico-pathological parameters which indicate metatasis or may predict TTP. The non-linear relationship may reflect different biological effects
of p27 on cell proliferation.
Disclosure: All authors have declared no conflicts of interest.