Expressão de p53, p16ink4a, p21Waf1/cip1, p21Ras e p27Kip1/cip1 em pacientes com adenocarcinoma gástrico com invasão da submucosa submetidos a gastrectomia com linfadenectomia D2 / Expression of p53, p16ink4a, p21Waf1/cip1, p21Ras, and p27Kip1/cip1 in patients exhibiting gastric adenocarcinoma with submucosa invasion submitted to gastrectomy with D2 linfadenectomy

Roberson Antequera Moron

INTRODUCTION: Early gastric cancer that invades the submucosa might have a lymphonodal involvement in about 20% of the cases. Gastrectomy and D2 linfadenectomy is a procedure that has presented mortality and morbidity. Determining which patients would have a greater risk of lymphonodal involvement would allow treatments with fewer complications. Recently, several authors reported a greater immunohistochemical expression of p53 and p21ras in advanced tumors with worst prognosis. It has also been reported the expression loss of p21wafl, p27kip1, and p16ink4a in advanced tumors, and, some studies also observed the relationship between the markers expression and lymphonodal involvement. METHODS: Eightyone patients who had undergone gastrectomy with D2 linfadenectomy from 1971 to 2004 were retrospectively studied. A new histopathological exam confirmed the diagnosis. Representative areas of both normal and metaplastic mucosa and of the tumor were selected for obtaining new blocks of tissue microarrays. The immunohistochemical expression of p21ras, p53, p21waf1/cip1, p27kip1 and p16ink4a in the tissues was evaluated. RESULTS: In normal, metaplastic and tumoral mucosa, p53 showed positivity in 53%, 87.3%, and 87.1% of the cases, respectively. In the same tissues, p21ras showed positivity in 85.3%, 86%, and 96.8%, respectively. The positivity of p16ink4a was 46.3%, 91.1%, and 86%, respectively. p27kip1 showed a positivity of 60%, 94.7%, and 95.3%, respectively. p21wafl/cip1 presented a positivity of 32.4%, 72.7%, and 71.4%, respectively. All tumors showed positivity for p53. Tumors with lymphonodal involvement presented hyperexpression (+4) of p53 in 47% of the cases versus 17% in patients who had not showed any involvement. No tumor with low positivity (0 and +1) of p53 showed lymphonodal involvement. No tumor with negative p21ras showed lymphonodal involvement. In patients with lymphonodal involvement, p21ras presented strong positivity (+2 and +3) in 88% of the cases versus 50% of the cases without lymphonodal involvement. There was a strong positivity (+2,+3, and +4) of p21wafl/cip1 in 71% of the tumors with lymphonodal involvement versus 28% in patients without involvement. It was not observed an expression loss of p21waf1, p27kip1 e p16ink4a in tumors with lymphonodal involvement. In normal mucosa, p16ink4a showed a hyper-expression (+4) in 20% of the cases with perineural invasion versus 0% of the cases without invasion. This same marker showed a hyper-expression in 50% of the cases with vascular invasion versus 0% of the cases without invasion. Tumors with Sm2 invasion pattern showed low positivity (0 and +1) of p27kip1 in normal mucosa in 89% of the cases versus 55% of the cases of Sm1 tumors. CONCLUSIONS: Higher expression of p53, p21ras, and p21wafl/cip1 in tumor showed a significant statistical relationship with lymphonodal involvement. A higher hyper-expression of p16ink4a in patients normal mucosa was related to perineural and vascular invasion of tumors

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