Expression of folate binding protein as a prognostic factor for response to platinum-containing chemotherapy and survival in human ovarian cancer.

Overexpression of the folate binding protein (FBP) is a common feature in epithelial ovarian cancer, but its prognostic significance is not clearly understood. We investigated whether FBP in epithelial ovarian cancer specimens is a predictor of response to chemotherapy and survival. Between 1990 and 1995, 99 patients with epithelial ovarian cancer underwent primary surgery and were treated with chemotherapeutic regimens including platinum derivatives. First-line chemotherapy was performed in 58 patients with residual disease and in 41 patients without residual disease after primary laparotomy. FBP expression level was determined in frozen specimens by cyto-fluorimetric assay using the MOv 18 monoclonal antibody (MAb). Association of FBP fluorescence index (FI) with clinical characteristics, response to chemotherapy, and survival was studied by univariate and multivariate analysis. In the 58 patients with residual disease after primary surgery, failure to respond to chemotherapy (complete or partial remission) was about 15-fold higher (95% confidence interval, 2.96-77.43) when tumors had FBP FI above the median value (FBP FI = 3.25). FBP FI was not a predictor of survival in the entire series of tumors (99 patients). However, in the subgroup of 58 patients with residual disease after primary surgery, survival analysis confirmed the disadvantage observed with respect to response to chemotherapy in patients expressing FBP FI above the median value (hazard ratio 2.01; 95% confidence interval 0.95-4.24). In conclusion, higher levels of FBP expression might be a predictor of chemotherapy response failure in ovarian cancer. In patients with residual disease after primary surgery, FBP FI could represent a valuable prognostic marker for survival.

Overexpression of folate binding protein in ovarian cancers.

The high affinity folate binding protein (FBP) is overexpressed in ovarian cancers. However, its role in the pathogenesis and biological behaviour of these neoplasms is not clearly understood. Using the monoclonal antibody (MAb) MOv 18 and cytofluorimetric analysis, we investigated FBP expression in frozen neoplastic tissues from 136 patients diagnosed with epithelial ovarian cancer. FBP values were compared with clinico-pathological characteristics (age, stage, histologic grade, histologic type, DNA ploidy, percentage of S-phase cells, and previous chemotherapeutic treatment). Some amount of FBP overexpression was observed in 122 of the 136 tumours examined. The overall mean value of FBP fluorescence index (FBP FI) was 5.6 (median 2.7; min 0.8--max, 78.9). By univariate analysis, FBP FI was overexpressed to a higher degree in ovarian neoplasms with high histologic grade, advanced stage, serous histology, aneuploid status, and high percentage of cells in S-phase. Of the total number (136) of cases, 106 had all the parameters assessed and were thus selected for stepwise selection procedure. The only significant independent variable was the percentage of S-phase cells, which accounted for about 31% of variance of FBP FI. Our results indicate that FBP is associated with parameters of biological aggressiveness in ovarian cancers.

Brief report: prognostic importance of cellular DNA content in T1-2 N0 laryngeal squamous cell carcinomas treated with radiotherapy.

One hundred fifty-two unselected, consecutive patients with T1-2N0 laryngeal squamous cell carcinoma received radical radiation therapy at the Division of Radiotherapy, Centro di Riferimento Oncologico, Aviano, Italy. Thirty-one (20.4%) of the patients showed disease recurrence or persistence (R/P) after radiotherapy. Flow-cytometric DNA ploidy measurements were performed in 72 cases; 20 had tumor R/P and 52 did not. Tumor R/P occurred more frequently (in 17 [85%] of 20 cases) in patients with diploid tumors. The hazard ratio of recurrence in diploid tumors as compared with aneuploid tumors, after inclusion of all the other significant prognostic factors in a Cox proportional hazards model, was 8.9 (P < .01). Therefore DNA ploidy seems to be an important marker of tumor R/P in patients with T1-2N0 laryngeal carcinoma after radiotherapy.

DNA flow cytometric evaluation of cell cycle distribution in ulcerative colitis: a proposed method for assessing severity of disease.

The assessment of disease severity in ulcerative colitis depends mainly on subjective variables, and an objective method of assessing mucosal inflammation is needed. Determination of the synthetic phase of the cell cycle is an accurate expression of inflammatory activity in the colonic mucosa. The aim of the study was to find out if the proliferative index or the synthetic phase (S phase) of the colonic mucosa of patients with ulcerative colitis, as evaluated by DNA flow cytometry, is a reliable and reproducible marker of disease activity. Sixty consecutive patients with ulcerative colitis of different degrees of activity were entered into the study and submitted to colonoscopy plus multiple rectal biopsies. Disease severity was defined for each patient by means of a clinical, endoscopic, and histological score. Flow cytometry was used to calculate the proliferative index and the S phase of the cell cycle. A statistically significant correlation (p < 0.001) was found between all indices of severity. It is suggested that flow cytometric evaluation of the cell cycle in the rectal mucosa may be an efficient method of assessing severity of disease and efficacy of medical treatment in ulcerative colitis.

P53 overexpression in human soft tissue sarcomas: relation to biological aggressiveness.

BACKGROUND: The tumor suppressor protein p53 is overexpressed in a large fraction of human tumors. It has been supposed that p53 abnormalities may be an early event that contributes to the neoplastic transformation; alternatively, p53 overexpression might be related to progression toward more aggressive tumor phenotypes. The aim of the present work was to better clarify the role of p53 overexpression in human soft tissue sarcomas (IISTS). DESIGN: p53 immunohistochemistry analysis using the Pab 1801 was performed in frozen samples of HSTS obtained from 61 patients. Tumors were classified according to the WHO criteria, histologic grading was based on the criteria of Enzinger and Weiss, and DNA ploidy and S-phase determination was performed by flow cytometrical analysis. RESULTS: Of all the HSTS we analyzed, p53 protein over-expression occurred more frequently in G3 grade tumors (p < 0.01), HSTS of III A-B stage (p = 0.02) and in aneuploid tumors (p < 0.01). CONCLUSIONS: The association of p53 overexpression with parameters of biological aggressiveness suggests an involvement of p53 in the neoplastic progression of HSTS. This assumption is supported by the findings that in tumors with a mixed diploid/aneuploid neoplastic cell population p53 protein expression was significantly (p < 0.01) higher in the aneuploid cell subpopulation. In conclusion, our study suggests that overexpression of p53 is present mainly in the most biologically aggressive forms of HSTS and may therefore represent a neoplastic progression index possibly useful for prognostic purposes.

Effect of short- and long-term treatment with omeprazole on cell cycle distribution in the gastric mucosa. Results of a flow cytometric study.

Omeprazole may exert an effect on gastric mucosal proliferation by inhibiting gastric acid secretion and increasing serum gastrin levels. It may also influence the kinetics of endocrine cells and the oxyntic mucosa. The aim of the present study was to evaluate the cell cycle in different gastric compartments following short- (1 month) and long-term (6 months) administration of two different dosages of omeprazole by means of a flow cytometric method. We also determined serum gastrin levels at the same time. No differences in cell cycle distribution of the antrum, body, and fundus were found in the two different dosage groups after 1 month of therapy, considering the synthetic phase (S-phase) of the cell cycle. A statistically significant increase in S-phase was reported after long-term therapy in the mucosa of the fundus and body of the stomach in both groups. Gastrin levels showed no clear correlation with cell cycle distribution variables. We postulate a proliferative adaptation of the oxyntic mucosa to long-term drug administration not mediated by gastrin influence.