Topoisomerase II alpha expression in normal, inflammatory, and neoplastic conditions of the gastric and colonic mucosa.

Topoisomerase II alpha (TP) excises and reconnects double-stranded super-coiled DNA during the replicative cell cycle. We studied the localization of TP and Ki-67 in inflammatory and neoplastic mucosal lesions of the stomach and of TP in similar conditions of the colon. TP expression was correlated with tumor stage, grade, and survival time in the colonic tumors to evaluate its potential utility as a predictive marker for clinical outcome. Forty-three sections of chronic gastritis, lesions indefinite for dysplasia, low- and high-grade dysplasia, and gastric adenocarcinomas were immunostained with antibody against TP and Ki-67. For the colon, 71 sections of normal mucosa, chronic colitis, hyperplastic polyps, adenomas, and carcinomas were examined; fresh tissue was analyzed by flow cytometry. Expression of TP in non-neoplastic gastric mucosa was maximal in neck/foveolar cells and focal in surface and deep gland cells. Increased surface and deep gland positivity was found in low-grade dysplasia and a diffuse distribution of positive cells in high-grade dysplasia and carcinoma. The Ki-67 staining pattern was similar. TP in non-neoplastic colon was restricted to the lower crypt zone; it was greatly expanded in the surface/upper crypt region in adenomas and was diffuse in carcinomas. Flow cytometric analysis revealed TP expression mainly in the S and G2/M phase, with higher labeling index in tumors. There was no correlation of TP with stage, grade, or survival times in the colonic tumors. Staining for TP and Ki-67 might help in the distinction of inflammatory and neoplastic lesions of the stomach and colon.

Gastric and hepatocellular carcinomas do not overexpress the same ribosomal protein messenger RNAs as colonic carcinoma.

The levels of a number of ribosomal protein mRNAs are reported to be increased in human colon cancer. We have assessed whether selected ribosomal protein mRNAs are overexpressed in other gastrointestinal malignancies, namely gastric and hepatocellular carcinomas. Subtracted complementary DNA libraries were generated from paired samples of human (a) colorectal carcinoma minus adjacent normal colonic mucosa and (b) hepatocellular carcinoma minus adjacent normal liver. Screening of approximately 3% of these library clones determined that ribosomal protein mRNAs encoding L18 and L37 (not previously reported) and P0 and S6 were overexpressed in one or the other library. Their complementary DNA inserts were then used as probes to evaluate their expression in a larger number of paired tumor/normal surgical samples of human colonic, gastric, and hepatocellular carcinomas, by Northern hybridization. The mRNA signal was greater in the colonic carcinoma than in paired adjacent normal colonic mucosa in 38 of 42 cases for P0 [tumor/normal (T/N) ratio = 3.0 +/- 0.3, mean +/- SE, P < 0.001] (G. F. Barnard, R. J. Staniunas, S. Bao, K. Mafune, J. L. Gollan, G. D. Steele, Jr., and L. B. Chen, Cancer Res., 52: 3067-3072, 1992), in 25 of 28 cases for L18 (T/N ratio = 3.7 +/- 0.5, P < 0.001), in 27 of 28 cases for L37 (T/N ratio = 5.3 +/- 0.4, P < 0.001), and in 24 of 28 cases for S6 (T/N ratio = 3.1 +/- 0.5, P < 0.01). The level of mRNA overexpression of L18 and S6 did not correlate with the Dukes' stage of disease. In hepatocellular carcinoma samples, using the same four ribosomal protein complementary DNA probes, only P0 mRNA was significantly increased (T/N ratio = 2.8 +/- 0.4, n = 6, P = 0.047). In gastric carcinoma samples, none of these mRNAs was increased (mean T/N ratios = 0.9-1.2, n = 6). Therefore, gastric and hepatocellular carcinomas do not overexpress the same ribosomal protein mRNAs as do colonic carcinoma.

Diagnosing proximal tubal obstruction: evaluation of peak intrauterine pressures using four common cannula techniques in extirpated uteri.

OBJECTIVE: To compare the ability of four chromotubation techniques to generate and maintain intrauterine pressures in the diagnosis of proximal tubal obstruction. METHODS: Sixteen extirpated uteri were used for this study. A pressure catheter was placed through the fundus into the endometrial cavity. Three cannulas were evaluated: 1) the Cohen cannula with hold and no-hold techniques, 2) the BARD cervical cannula (dual intrauterine and intracervical balloons), and 3) the Harris-Kronner uterine manipulator-injector catheter with an intrauterine balloon. Intrauterine pressures were monitored while warm saline was infused. The studies were performed with the tubes obstructed, and measurements of peak attainable intrauterine pressures were recorded. Data were analyzed by t test, with significance set at P < .05. RESULTS: Peak intrauterine pressures for the four groups were as follows: 1) Cohen cannula, not holding, 40.7 +/- 5.1 mmHg; 2) Cohen cannula, holding in place, 63.6 +/- 5.3 mmHg; 3) BARD cannula, 112.4 +/- 3.5 mmHg; and 4) Harris-Kronner cannula, 106.3 +/- 4.3 mmHg. The BARD and Harris-Kronner cannulas achieved significantly higher intrauterine pressures than either method of using the Cohen cannula (P < .001). There was no statistically significant difference between the BARD and Harris-Kronner cannulas. CONCLUSION: Significant differences in achievable intrauterine pressures were demonstrated among catheters in our in vitro model. Based on these findings, we believe that the BARD, Harris-Kronner, or other intrauterine balloon-type cannula should be used before diagnosing proximal tubal obstruction.