Expression of p21(WAF1/CIP1) and p53 proteins in gastric carcinoma: its relationships with cell proliferation activity and prognosis.

The expressions of p21(WAF1/CIP1), p53 proteins, and Ki-67 antigen were investigated immunohistochemically in 190 primary gastric carcinomas. Of the 190 tumors, 40.5% positively expressed p21(WAF1/CIP1) and 42.1% positively expressed p53. The expression of p21(WAF1/CIP1) was significantly associated with clinicopathological factors including gender, tumor size, status of lymph node, and clinicopathological stage (P<0.05 for all), but p21(WAF1/CIP1) expression showed no clear correlation with Ki-67 labeling index. The mean Ki-67 labeling index was significantly higher in p53-positive cases than p53-negative cases (P<0.0001). However, among the clinicopathological factors examined, expression of p53 correlated only with age. Univariate and multivariate survival analyses revealed that clinicopathological stage (P<0.001) and expression status of p21(WAF1/CIP1) (P<0.05) were independent prognostic factors. Neither the expression status of p53 nor the Ki-67 labeling index, however, influenced the prognosis of patients with gastric cancer.

Expression of p53 protein as a prognostic indicator of reduced survival time in diffuse-type gastric carcinoma.

To determine whether p53 expression is different in intestinal and diffuse types of gastric carcinoma, we investigated p53 immunohistochemical expression in 178 primary gastric carcinomas. Overexpression of p53 was observed in 50 out of 100 intestinal-type tumors (50.0%) and in 27 out of 78 diffuse-type tumors (34.6%). A significant difference was found in the timing of p53 overexpression between the two types of carcinomas. Overexpression of p53 occurred often in the early stage of intestinal-type tumors, and there was no significant difference in expression between early and advanced cancers. In contrast, p53 overexpression did not occur often in the early stage of diffuse-type tumors, but it increased progressively as the tumor advanced. Analysis of patient survival revealed that p53 overexpression correlates significantly with a poor prognosis in diffuse-type gastric carcinoma (P = 0.003) but not in intestinal-type. Multivariate analysis showed that only pathological stage was an independent prognostic indicator. Our results suggest that p53 overexpression plays a different role in tumor carcinogenesis and progression of these two types of gastric cancers.

Combined examination of p27(Kip1), p21(Waf1/Cip1) and p53 expression allows precise estimation of prognosis in patients with gastric carcinoma.

AIMS: In order to estimate the prognostic values of p27(Kip1), p21(Waf1/Cip1), and p53, alone and in combination, we investigated immunohistochemically the expression of p27(Kip1), p21(Waf1/Cip1), and p53 proteins in gastric carcinomas. METHODS AND RESULTS: The expression of p27(Kip1), p21(Waf1/Cip1), and p53 was immunohistochemically examined in 140 gastric carcinomas. Positive expression of p27(Kip1) and p21(Waf1/Cip1) correlated significantly with a favourable prognosis (P < 0.05), whereas, positive expression of p53 tended to correlate with poor prognosis. Multivariate survival analysis revealed that TNM stage of tumour (P < 0.001), lymph node state (P=0.005), and p27(Kip1) expression (P=0.006) were independent prognostic factors. A striking stratification of mortality rate was found when patients were divided into four groups according to the expression of p21(Waf1/Cip1) and p27(Kip1). The mortality rate was higher in patients with both p21(Waf1/Cip1)- and p27(Kip1)-negative gastric carcinoma than in patients with one or both positive carcinomas (P < 0.01). In addition, if the four p21(Waf1/Cip1)/p27(Kip1) groups were compared based on p53 status, p53+ cases tended to have a higher mortality rate than p53- cases. CONCLUSION: Our results suggest that low expression of both p27(Kip1) and p21(Waf1/Cip1), could be useful as markers of poorer prognosis, and the combined examination of p27(Kip1), p21(Waf1/Cip1) and p53 expression allows reliable estimation of prognosis for patients with gastric carcinoma.

[Prediction of performance status after pneumonectomy].

To predict performance status (P.S.) following pneumonectomy, patients with lung carcinoma underwent pre-surgical pulmonary function tests with spirometry and unilateral pulmonary artery occlusion test (UPAO test). Between 1980 and 1991, twenty-nine patients who had survived more than six months after surgery were selected for the study. These patients were divided into two groups according to P.S. measured at six months after surgery: 16 patients with P.S. 0 to 1 were in Group A, and 13 patients with P.S. 2 to 3 were in Group B. The results of the following tests obtained prior to surgery were compared for the two groups to predict post-surgical P.S.; vital capacity (VC), VC/m2, forced expiratory volume in 1 second (FEV1.0), FEV1.0/m2, predicted VC/m2 and predicted FEV1.0/m2 calculated with residual pulmonary segments, mean pulmonary arterial pressure (PPA) before UPAO and 15 minutes after UPAO, total pulmonary vascular resistance (TPVR) before and during UPAO, and rate of changes in PPA and TPVR. Results obtained were as follows: Group B demonstrated significantly higher TPVR (p < 0.05) before the UPAO, PPA (p < 0.05) and TPVR (p < 0.002) during UPAO, and rate of change in TPVR (p < 0.02) than those in Group A. There were no significant differences between the two groups for other test results. From these results, lowering of post-surgical P.S. might be predicted when the TPVR during UPAO was 350 dyne.sec.cm-5/m2 or more.

[A case of hyperosmolar nonketotic coma occurring during chemotherapy in lung cancer].

A 61-year-old woman was admitted to our hospital because of hoarseness and abnormal shadow on chest X-ray. We diagnosed this patient as large cell carcinoma of the right upper lobe of the lung; T3N3M1 Stage IV. She was treated with OK-432, CDDP and CQ. On the 6th day after 2nd cycle chemotherapy, she was confused, and we diagnosed her as a case of hyperosmolar nonketotic coma (HNC) on the 7th day. Unfortunately, she died on the 8th day, after 20 hours of treatment for HNC. She suffered from chronic dehydration due to trouble with left recurrent nerve palsy. Although continuous intravenous hyperalimentation was used, she had severe HNC. HNC might be one complication in chemotherapy for patients with malignancy.