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Biomedical subjects

U Stendahl

Publications and source records attributed to U Stendahl.

90 records · Page 5Linked to original sources

Influence of oestrogen on growth of endometrial carcinoma.

The influence of endogenously produced oestrogen on the growth of endometrial carcinoma was studied in postmenopausal 128 patients with endometrial adenocarcinoma. Plasma concentration of oestrone (E1) and oestradiol (E2) showed wide variations. Hormone levels were analysed in relation to growth rate, expressed as S-phase rate measured by flow cytometry, and to ploidy level. When the whole unclassified group was studied, no statistical relationship between E1 and E2 levels and S-phase rates were found. However, when peridiploid tumors (1.8-2.2 c) were divided according to histopathological grades, well differentiated tumors with low oestradiol concentrations (less than 60 pmol/I) had significantly lower S-phase rates than those with higher oestradiol levels (p less than 0.01). Aneuploid tumors showed high S-phase rates regardless of plasma oestradiol concentrations.

Aged↗

Oestrogens and clinical characteristics in endometrial carcinoma.

Serum concentrations of endogenously produced oestrogens were studied in 128 postmenopausal women with endometrial carcinoma. Radioimmunoassays of serum oestrone (E1) and oestradiol (E2) were performed on admission to hospital. Results showed a wide variation in serum concentrations of E1 and E2 in patients with endometrial carcinoma. Some patients had high E1 values and low E2, while none of the patients had low E1 and high E2 values. Hormonal levels were correlated with increasing BMI (E1; p less than 0.000001; E2; p less than 0.000001). Uterine cavity depth was also related to both E1 and E2 (E1; p less than 0.00001; E2; p less than 0.0003). Concentrations of E1 and E2 were higher in diabetic women than in the non-diabetic. (E1; p less than 0.002; E2; p less than 0.01). E2 concentration was higher in hypertensive patients than in the non-hypertensive patients (p less than 0.04). Parameters such as age, menstrual history, clinical stage and histopathology showed no significant correlation with hormone concentrations.

Adenocarcinoma↗

The reproducibility of flow cytometric analyses in human tumors. Methodological aspects.

Various methodological aspects of flow cytometry were studied in material from endometrial carcinoma, ovarian tumors and bladder carcinoma. Measurements of identical samples on two different occasions gave an excellent correlation of the obtained DNA values, r = 0.997 and a good reproducibility of the S-phase rate, r = 0.87. In large tumors different DNA values were found in 5/36 cases when central and surface biopsies were compared (indicating tumor heterogeneity) which stresses the importance of multiple biopsies. The S-phase rate of the surface biopsies was generally higher. Comparing staining with ethidium bromide and DAPI, a good correspondence of ploidy determinations in human bladder tumors was found, provided that diploid cells from the normal tissue component were used as internal reference. When ethidium bromide staining was used, there was a good agreement between the values of tumor ploidy obtained by external standardization using lymphocytes and internal standardization using diploid tumor cells, respectively. In DAPI staining with lymphocytes as an external standard the tumor ploidy was systematically overestimated by about 10% due to suboptimal staining of lymphocytes after 3 hours. This difference decreased after 18 hours of staining. Determination of S-phase fraction showed a good correlation between DAPI and ethidium bromide stained bladder tumor samples (r = 0.86). Human lymphocytes as an external standard showed good reproducibility. In conclusion, flow cytometric measurements of the ploidy level and S-phase rate are highly reproducible provided that tumor heterogeneity is taken into account and proper preparation and standardization methods are used.

DNA, Neoplasm↗

Blood group antigen expression and prognosis in squamous cell carcinoma of the uterine cervix.

Immunohistochemical staining of invasive squamous cell carcinoma of the uterine cervix, stage IB to IV, with monoclonal antibodies against blood group antigens shows retained expression of the antigen in two thirds of the patients, regardless of stage. The over-all 5 year survival of the 115 patients was 60%, 71% in the antigen positive group, 37% in the antigen negative group. The loss of blood group antigen expression thus implies a worse prognosis in all stages of cervical carcinoma and could be used as a predictive marker.

ABO Blood-Group System↗

Age, menopausal status and DNA-content in endometrial adenocarcinoma.

In a prospective study of 283 women with endometrial carcinoma, 29 of whom were premenopausal and 254 postmenopausal, the DNA content and S-phase rate were measured by flow cytometry. Over 90% of the tumors in premenopausal women were peri-diploid and the remaining tumors were tetraploid, whereas 23% of the tumors in post-menopausal women were grossly aneuploid (p less than 0.01). Similar differences were found between women younger or older than 50 years. The results indicate that the hormonal status and/or age are of importance for the development of genetically different forms of endometrial carcinomas, as judged from the DNA-distribution.

Adenocarcinoma↗

Differences in DNA content and proliferation rate between adenocarcinomas of the uterine cervix and corpus.

The DNA content and the S-phase rate of 26 cervical adenocarcinomas and 100 endometrial adenocarcinomas, determined by flow cytometry, were compared. Statistically significant differences in DNA patterns were found, although only pure adenocarcinomas were studied in both groups. Peri-diploid values (1.8c-2.2c) were less common in cervical adenocarcinomas (38%) than in endometrial carcinomas (65%) (p less than 0.05). Six (23%) of the cervical carcinomas and 8 (8%) of the endometrial carcinomas had two detectable stem lines. The mean S-phase rate was significantly higher in adenocarcinomas of the uterine cervix than in endometrial carcinomas (p less than 0.02). The dominance of aneuploid values, the high proportion of polyclonal tumors and the high S-phase rates of the cervical adenocarcinomas have more similarities with the DNA patterns of cervical squamous cell carcinomas than with those of endometrial adenocarcinomas.

Adenocarcinoma↗

Flow cytometry in invasive endometrial carcinoma. Correlations between DNA content S-phase rate and clinical parameters.

In a prospective study including 185 women with endometrial adenocarcinoma, the DNA-content and the S-phase rate were measured by flow cytometry. The tumors of 138 (75%) patients were peridiploid and those of 47 (25%) were grossly aneuploid. Aneuploid tumors were more common in poorly differentiated tumors than in well and moderately differentiated tumors (p less than 0.0001). S-phase rates were evaluable in 148 (80%) tumors. High S-phase rates were more frequent in stages III + IV than in stages I + II (p less than 0.05) and were also more common in poorly differentiated tumors than in moderately and well differentiated tumors (p less than 0.05). Ploidy levels and S-phase rates were not significantly correlated with age or menopausal status. During the follow-up time (6 to 38 months), 19 patients died of their disease. The number of deaths registered was significantly higher among patients with aneuploid tumors than among patients with peridiploid tumors (p less than 0.002). The proportion of tumors with high S-phase rates was significantly higher than that of tumors with low S-phase rates (p less than 0.0001). These preliminary results indicate that patients with aneuploid tumors or tumors with high S-phase rates are at high risk for early recurrences.

Aged↗

Residual myometrial invasion after intracavitary irradiation of endometrial adenocarcinoma stages I and II. Relations to DNA content and S-phase rate.

The DNA content and the S-phase rate were determined by flow cytometry in 129 women with endometrial adenocarcinoma in stages I and II. Aneuploidy and elevated S-phase rates were statistically correlated to loss of histopathologic differentiation. After preoperative intracavitary irradiation and surgery, the occurrence of residual myometrial invasion was studied. Residual myometrial invasion was found in 28 (22%) cases. In 17 (17%) of the peri-diploid (1.8c-2.2c) and in 11 (38%) of the aneuploid tumors, respectively, the myometrium was invaded (p less than 0.05). No statistical correlation was found between mean S-phase rate and myometrial invasion. The difference in residual myometrial invasion found between aneuploid and peri-diploid tumors after intracavitary treatment may reflect a primary difference in the tendency to invade the myometrium or a difference in responsiveness to radiotherapy.

Adenocarcinoma↗

Blood group isoantigen expression during tumour progression of cervical neoplasia.

Twenty-nine cases of microinvasive squamous and 38 cases of progression from preinvasive to invasive carcinoma of the cervix were immunostained with monoclonal antibodies against blood group isoantigens for expression in normal, dysplastic and neoplastic epithelium. The results show a varying staining pattern without correlation to tumour progression, recurrence or survival.

ABO Blood-Group System↗

Blood group antigens in relation to DNA content, S-phase rate and heterogeneity, and their prognostic values in cervical carcinoma.

Evaluations were made of the expression of blood group antigens, DNA content and S-phase rate in a prospective study of 97 patients with squamous cell carcinoma of the uterine cervix. No correlation was found between loss of ABH expression and ploidy level or the degree of proliferation, whereas correlations were found to age and stage. In 11 (42%) of 26 tumors with two or three detectable stemlines, distinct areas with disparate ABH staining patterns were found, indicating genotypic and phenotypic heterogeneity within these tumors. In tumors with one stemline significantly fewer such tumors were found (p less than 0.01). Twenty-four early recurrences (within 20-36 months) after treatment were found. High S-phase rates (greater than 20%) were associated with a significantly increased recurrence rate (p less than 0.05). Loss of ABH antigen expression or ploidy level were not statistically correlated to early recurrences.

ABO Blood-Group System↗

Blood group isoantigen and involucrin expression in cervical intraepithelial neoplasia.

258 patients with dysplastic cervical lesions reclassified as CIN 1-3 and AIM 1-3 and with up to ten years of follow-up were immunostained with monoclonal antibodies against blood group isoantigens and involucrin for expression in normal and dysplastic squamous epithelium. The results show a varied staining pattern with a majority of unchanged staining properties in normal and dysplastic epithelium, the same frequency of increase as decrease in dysplasia and no correlation to progression or recurrence, in variance with previous reports.

ABO Blood-Group System↗

S-phase rate as a predictor of early recurrences in carcinoma of the uterine cervix.

Flow cytometric measurements of ploidy level and S-phase rate were performed in a prospective study of 165 patients with cervical squamous cell carcinoma. Patients were followed-up for 24 months after initial treatment. There was no significant difference in recurrence rate between patients with peri-diploid tumors (1.8c-2.2c) and aneuploid tumors. The S-phase rate (evaluable in 133 cases), which previously has been studied only occasionally in cervical carcinomas, was correlated with early relapses. Significantly more relapses were found in tumors with S-phase rates greater than or equal to 20% than among tumors with S-phase rates less than 20% (chi 2 = 9.54, p less than 0.01). A higher relapse rate among tumors with S-phase rates greater than or equal to 20% was found even after taking staging into consideration (Cochran-Mantel-Haenszel test, p less than 0.01). Thus, besides staging, evaluation of the S-phase rate yielded additional prognostic information.

Carcinoma↗

Polyclonal cervical tumors detected by flow cytometry.

In a prospective study, the tumors of 167 patients with invasive squamous cell carcinomas of the uterine cervix were investigated by flow cytometric measurements of the DNA-content. In 37 patients (22%) 2 or more stemlines could be detected, indicating clonal heterogeneity. The proportion of multiple stemlines was equal in stages IB to III but significantly higher in stage IV (p less than 0.01). In 14 of the 37 polyclonal tumors the DNA-value of the second peak was twice the value of the first peak, suggesting possible polyploidization. For those tumors with evidence of polyploidization that had values in the diploid, tetraploid or octaploid region (n = 9) the mean age was 35.6 +/- 11.7 years and for grossly aneuploid tumors (n = 5) the mean age was 73 +/- 12.6 years. The differences of mean age between the two groups differed significantly (p less than 0.001). Flow cytometry proved to be a useful, rapid, and sensitive method for detection of multiple stemlines.

Adult↗

Peritoneal fluid and HCG influence on steroid production from ovarian tumor tissue, in vitro.

Steroids are produced by malignant and benign epithelial ovarian tumor tissue in vitro, but the regulation is unknown. The effect of peritoneal fluid and beta-HCG on steroid production was analysed. Tissue from 17 malignant or benign epithelial ovarian tumors and 6 normal postmenopausal ovaries were incubated. In 11 cases tissue was incubated with and without addition of the patient's own peritoneal fluid (Part I). Tissue from 22 ovaries was incubated with and without HCG (100 IU/ml medium), (Part II). Furthermore, the release from tumorous and control ovaries of beta-HCG, progesterone, androstenedione and estradiol measured using radioimmunoassay (Part III). Peritoneal fluid stimulated the release of progesterone from both malignant and benign tissue and androstenedione or estradiol stimulated release from benign tissue (Part I). There was no stimulatory effect of HCG on steroid release from malignant tissue. HCG stimulated release of estradiol in benign tissue (Part II). All malignant tumors and 4 out of 6 benign tumors released beta-HCG (Part III). There seems to exist factors in peritoneal fluid which are able to stimulate steroid production from ovarian tumors.

Adult↗

Sex steroid hormones and receptors in relation to S-phase fraction and ploidy level in endometrial carcinoma.

Although endogenous hormones exert an effect on the proliferation of endometria adenocarcinoma, there also seems to be an autonomous proliferation of the malignant cells. Simultaneous measurement of endocrine and cell proliferation related variables in endometrial adenocarcinoma specimens are expected to increase the understanding of factors responsible for progression or regression of this form of cancer. Sixty patients with endometrial adenocarcinoma were examined. The following parameters were analysed: endogenous plasma concentration of oestradiol, oestrone, progesterone, androstenedione and testosterone; S-phase fraction (SPF) and ploidy level, by flow cytometry; oestrogen and progesterone receptors, by immunohistochemistry. The oestrogen receptor positive tumours had a lower S-phase fraction that receptor negative tumours (p < 0.05), but SPF was still under the mean for the whole group. ER positive tumours were all diploid, while progesterone receptors were found also in aneuploid tumours. The presence of PR did not relate to lower SPF, but in an earlier study increased progesterone concentration was found to relate to lower SPF, and the antiproliferative effect of progesterone was also seen in more malignant tumours.

Adenocarcinoma↗

EGF/TGF-alpha and progesterone in urine of ovarian cancer patients.

EGF/TGF-alpha and progesterone were measured in the urine of 74 ovarian carcinoma patients, 21 postmenopausal women with non-gynecological disseminated cancer, 20 premenopausal and 20 postmenopausal controls. Radically operated women excreted significantly less EGF/TGF-alpha into urine than women with residual tumour mass. The patients who died from ovarian carcinoma had significantly higher concentrations of growth factor in urine than patients who were alive and disease-free at follow-up. The highest urinary concentrations were found in the premenopausal control group and among women with non-ovarian malignancies. A significant correlation between concentrations of progesterone and EGF/TGF-alpha in urine was noted.

Adult↗

Progesterone and estradiol stimulate release of epidermal growth factor/transforming growth factor alpha by ovarian tumours in vitro.

Previous studies have demonstrated locally increased steroid production and release of EGF/TGF-alpha in ovarian carcinomas. The influence of added steroid hormones on EGF-like activity in ovarian tumours in vitro was investigated. Using radioreceptor assay, EGF-like activity was measured in media from incubations of postmenopausal ovaries, benign and malignant epithelial ovarian tumours from 27 patients. The 3-hour incubations were performed with and without addition of progesterone, testosterone or estradiol. Addition of progesterone and estradiol significantly increased the release of EGF/TGF-a from benign tumour tissue but did not stimulate release from control ovaries. A stimulating effect was also noted for malignant tumour tissue but the increase was not significant. Addition of EGF or IGF-1 did not affect the release of steroid hormones from ovarian tumours. A positive correlation between progesterone and EGF-like activity was found in incubation media of peritoneal fluid cells from cancer patients.

Adult↗

Prospective malignancy grading, flow cytometry DNA-measurements and adjuvant chemotherapy for invasive squamous cell carcinoma of the uterine cervix.

In a prospective study comprising 310 consecutive patients with carcinoma of the cervix, FIGO stages I-IV, the prognostic significance of clinical and flow cytometric variable was evaluated in a univariate and multivariate analysis. The parameters studied included stage according to FIGO, age, histopathologic grade according to Ackerman and MGS scores, DNA ploidy, S-phase fraction as well as treatment with radiation only, surgery only or a combination thereof as well as adjuvant chemotherapy. Univariate analysis showed that patients in FIGO stages IA-IIA with MGS up to 14 points survived significantly better than other groups. MGS parameter mitosis, vascular invasion and type of invasion predicted survival as did clinical stage. Diploid cases with SPF > 15% survived less than remaining other cases. Multivariate analysis not including treatment indicated that FIGO stage and diploid cases with SPF > 15% predicted survival but not total MGS score and age. When treatment for FIGO stages IA-IIA was included, elderly women had a worse prognosis. Adjuvant chemotherapy, surgical alone or radiation alone did not demonstrate any differences within groups. In Figo stages IIB-IV, cases with radiotherapy only survived significantly better than patients with other treatment schedules. The frequency of low malignancy patients (< MGS 16) in relation to year of initial diagnosis was found to have decreased between years 1967 and 1988, probably as a result of screening activities.

Adult↗