Loss of p27Kip1 expression is a strong independent prognostic factor of reduced survival in N0 gastric carcinomas.
BACKGROUND
p27KiP1 is a cyclin-dependent kinase inhibitor and is a potential tumor suppressor gene. Reduced expression of p27Kip1 is a powerful negative prognostic marker in primary lung, breast, colon, bladder, and prostate carcinomas. In the current study, the prognostic value of p27Kip1 in gastric cancer was evaluated and compared with other histopathologic parameters and p53 expression.


METHODS
p27Kip1 and p53 protein expression were determined by immunohistochemistry in 96 gastric carcinomas. The tumors were from a low incidence population and were selected for the absence of lymph node involvement.


RESULTS
Reduced expression of p27KiP1 (< or = 50% positive cells) and nuclear p53 accumulation (> 30% positive cells) were observed in 67 (69.8%) and 9 (9%) tumors, respectively, and were not related to either the pT category or tumor histology. Kaplan-Meier analyses revealed a significant impact on survival by p27Kip1 (P = 0.0001 by log rank test), p53 (P < 0.0001) expression, and the pT category (P < 0.0001). On multivariate analysis, reduced p27Kip1 protein expression was the strongest independent predictor of reduced survival (P = 0.005; relative risk = 3.348) out weighing the pT category (P = 0.010; relative risk = 2.257) and p53 overexpression (P = 0.016; relative risk = 2.618).


CONCLUSIONS
These data indicated that immunohistochemical detection of p27Kip1 could help to identify gastric carcinoma patients who are at high risk of death, even in the absence of lymph node involvement, and who might benefit from an adjuvant treatment following surgery.
Sgambato
A
A
Centro di Ricerche Oncologiche, Giovanni XXIII, Institute of General Pathology, Catholic University, Rome, Italy. crogxxiii@rm.unicatt.it
Migaldi
M
M
Leocata
P
P
Ventura
L
L
Criscuolo
M
M
Di Giacomo
C
C
Capelli
G
G
Cittadini
A
A
De Gaetani
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27