Does the expression of cyclin E, pRb, and p21 correlate with prognosis in gastric adenocarcinoma?
BACKGROUND
Cyclin E is a protein that plays a key role in the G1 --> S transition of the normal cell cycle. The product of retinoblastoma gene (pRb) is the master regulator of entry into the cell cycle and p21 protein is a cyclin-dependent kinase inhibitor that disturbs the progression through the cell cycle. The expression of these proteins, among many others, is being deregulated in tumorogenesis. The aim of this study was to investigate whether cyclin E, pRb, and p21 can be used as prognostic indicators in gastric cancer.


METHODS
Fifty-six patients with gastric adenocarcinoma, who underwent curative resection, constituted the group of our study. The immunohistochemical expression of cyclin E, pRb, and p21 proteins was examined and correlated with clinical-pathological parameters and survival.


RESULTS
Positive cyclin E immunostaining was observed in 23 tumors (41.1%). It was associated with intestinal Lauren classification (P=0.003), nodal infiltration (P=0.0025), size of the tumor >5 cm (P=0.032), and lymphatic (P=0.042) and vascular invasion (P= 0.0029). Nevertheless, the survival of patients with positive cyclin E tumors was not significantly shorter than that of negative patients. Positive pRb immunostaining was found in 24 (42.9%) cases and it was associated with the absence of Helicobacter pylori (P=0.044), whereas positive p21 immunostaining was found in 21 tumors (37.5%) and it was associated with less depth of gastric wall infiltration (P=0.001), the absence of lymphatic (P=0.019) and vascular infiltration (P=0.024), and the absence of liver metastasis (P=0.044). Cyclin E expression was associated with pRb expression (P=0.023), but was correlated inversely with p21 expression (P=0.009). The survival of patients with pRb-positive tumors and the survival of patients with p21-positive tumors were significantly longer than that of negative patients (P= 0.0044 and P<0.001, respectively).


CONCLUSIONS
The expression of cyclin E could not predict the survival in this series of patients with gastric cancer, whereas the expression of pRb and p21 was associated with a favorable prognosis.
Kouraklis
Gregory
G
2nd Department of Propedeutic Surgery, Medical School University of Athens, Athens, Greece. gkouraklis@hotmail.com
Katsoulis
Iraklis E
IE
Theocharis
Stamatios
S
Tsourouflis
Gerasimos
G
Xipolitas
Nikos
N
Glinavou
Andromahi
A
Sioka
Chrysa
C
Kostakis
Alkiviadis
A
D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D019927:Cyclin E / Q000032:analysis*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis*; D005260:Female; D005743:Gastrectomy; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000032:analysis*; D010766:Phosphorylation; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D016160:Retinoblastoma Protein / Q000032:analysis*; D018570:Risk Assessment; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; C475820:CCNE1 protein, human; C493956:CDKN1A protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015513:Oncogene Proteins; D016160:Retinoblastoma Protein