Immunohistochemical analysis of cell cycle-related molecules in gastric carcinoma: prognostic significance, correlation with clinicopathological parameters, proliferation and apoptosis.

OBJECTIVE We aimed to investigate the biological significance of cell cycle regulators in gastric carcinoma. METHODS Immunohistochemistry and TUNEL staining were performed on tissue array slides containing 293 gastric carcinoma specimens. The relationship between the protein expression of each of the cell cycle regulators and prognosis, clinicopathological features, proliferation, or apoptosis was evaluated. RESULTS The nuclear immunoreactivity for cyclin D1, cyclin E, p21, and p27 was observed in 22, 14, 31 and 27% of cases, respectively. The expression of cyclin D1, p21, or p27 positively correlated with early pTNM stages, tumor cell proliferation (represented by Ki-67 labeling) and good prognosis, whereas it inversely correlated with the lymph node metastasis (p < 0.05). On the other hand, p27 expression inversely correlated with the apoptosis index represented by TUNEL staining (p < 0.001). In addition, the expression of cyclin D1 positively correlated with that of p21 or p27 (p < 0.05). CONCLUSIONS Our results showed that the expression of cyclin D1, p21 and p27, alone or in combination, are early events in gastric tumorigenesis and may serve as a candidate molecular marker for the early gastric carcinoma.