Biomedical subjects

K Urbański

Publications and source records attributed to K Urbański.

At least 19 recordsLinked to original sources

PubMed2006

BRCA1-positive breast cancers in young women from Poland.

We identified 4316 unselected incident cases of early-onset breast cancers (<51 ears of age at diagnosis) in 18 Polish hospitals between 1996 and 2003. We were able to obtain a blood sample for DNA analysis from 3472 of these (80.4%). All cases were tested for the presence of three founder mutations in BRCA1. The proportion of cases with a BRCA1 mutation was 5.7%. The hereditary proportions were higher than this for women with breast cancer diagnosed before age 40 (9%), for women with cancer of medullary or atypical medullary histology (28%), for those with bilateral cancer (29%) or with a family history of breast or ovarian cancer (13%). It is reasonable to offer genetic testing to women with early-onset breast cancer in Poland.

Adult↗

PubMed2005

A common variant of CDKN2A (p16) predisposes to breast cancer.

BACKGROUND: A common missense variant of the CDKN2A gene (A148T) predisposes to malignant melanoma in Poland. An association between malignant melanoma and breast cancer has been reported in several families with CDKN2A mutations, OBJECTIVE: To determine whether this variant also predisposes to breast cancer. METHODS: Genotyping was undertaken in 4209 cases of breast cancer, unselected for family history, from 18 hospitals throughout Poland and in 3000 controls. RESULTS: The odds ratio (OR) associated with the CDKN2A allele for women diagnosed with breast cancer before the age of 50 was 1.5 (p = 0.002) and after age 50 it was 1.3 (p = 0.2). The effect was particularly strong for patients diagnosed at or before the age of 30 (OR = 3.8; p = 0.0002). CONCLUSIONS: CDKN2A appears to be a low penetrance breast cancer susceptibility gene in Poland. The association should be confirmed in other populations.

Adult↗

PubMed2005

Breast cancer predisposing alleles in Poland.

Mutant alleles of several genes in the DNA repair pathway have been found to predispose women to breast cancer. From a public health perspective, the importance of a given allele in a population is determined by the frequency of the allele and by the relative risk of breast cancer that it confers. In Poland founder alleles of the BRCA1, CHEK2 and NBS1 genes have been associated with an increased risk of breast cancer, but the relative contribution of each of these alleles to the overall breast cancer burden has not yet been determined. We screened 2012 unselected cases of breast cancer and 4000 population controls for 7 different mutations in these genes. Overall, a mutation was found in 12% of the cases and in 6% of the controls. Mutations in BRCA1 and CHEK2 contributed in approximately equal measure to the burden of breast cancer in Poland. A BRCA1 mutation was present in 3% of the cases. The missense BRCA1 mutation C61G was associated with a higher odds ratio for breast cancer (OR=15) than were either of the truncating BRCA1 mutations 4153delA (OR=2.0) and 5382insC (OR=6.2). In contrast, a higher odds ratio was seen for truncating CHEK2 mutations (OR=2.1) than for the missense mutation I157T (OR=1.4). This study suggests that cancer risks may be specific for particular alleles of a susceptibility gene and that these different risks should be taken into account by genetic counselors.

Adult↗

PubMed2004

TP53 status determines clinical significance of ERBB2 expression in ovarian cancer.

ERBB2 expression has been found in 19 to 44% of ovarian carcinomas; however, its predictive value has not been demonstrated, and trastuzumab has not found clinical application in ovarian cancer patients. We evaluated clinical significance of ERBB2 expression in relation to TP53 accumulation in ovarian carcinoma patients treated with platinum-based regimens. Immunohistochemical analysis with CB11 and a novel NCL-CBE356 antibody (against the internal and external domains of ERBB2, respectively) was performed on 233 tumours (FIGO stage IIB-IV); the US Food and Drug Administration-approved grading system with 0 to 3+ scale was used for evaluation, and the results were analysed by the Cox and logistic regression models. In all, 42% of the tumours expressed (category 1+, 2+ or 3+) either CB11 or CBE356 or both (CB11/CBE356 parameter). Associations between ERBB2 expression and clinical factors were observed only if tumours with staining category 1+ were grouped together with tumours showing staining categories 2+ and 3+. CB11/CBE356 parameter had a better predictive value than CB11 alone. CB11/CBE356 expression was negatively associated with platinum sensitivity (PS) in the TP53(-) group (P=0.022) and with disease-free survival (DFS) in the TP53(+) group (P=0.009). Our results may suggest that trastuzumab should be given postoperatively to patients with TP53(-)/ERBB2(+) ovarian carcinomas to enhance PS, and after completion of chemotherapy to patients with complete remission and TP53(+)/ERBB2(+) carcinomas to extend DFS time (in total to 30.4% of all patients analysed). Thus, novel criteria for ovarian cancer patient inclusion for clinical trials with trastuzumab should be considered and tested.

Adult↗

PubMed2003

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen.

In cell line studies, BCL-2, BAX, as well as novel MEK1 protein levels have strong influence on ovarian cancer response to cisplatin-based chemotherapy. However, such associations have not been demonstrated clinically. We evaluated prognostic/predictive significance of these proteins with regard to TP53 status. Immunohistochemical analysis was performed on 229 ovarian carcinomas FIGO stage IIB-IV treated with platinum-based chemotherapy; the results were analysed by the Cox and logistic regression models. Clinical parameters (residual tumour size, patient age, FIGO stage) were the only indicators of overall survival (OS) and the strongest predictors of complete remission (CR). On the other hand, BAX expression was the strongest (P=0.005) or the only (in FIGO IIIC, P=0.02) prognostic indicator of disease-free survival (DFS) in the TP53(+) group. TP53(+) and TP53(-) ovarian carcinomas differed in clinical and molecular prognostic and predictive factors. Another novel finding is that CR was negatively influenced by high BAX expression in all patients group (P=0.047) and by BCL2 expression in the TP53(-) group (P=0.05). High MEK1 expression was associated with endometrioid and clear cell carcinomas (P=0.049); its loss was found with advancing FIGO stage (P=0.002). Our results suggest that binomial TP53 status divides ovarian carcinomas into two biologically distinct groups. BAX expression is an important factor of DFS in the TP53(+) group. BCL-2 and BAX, but not MEK1 expressions have predictive value in ovarian cancer patients treated with platinum-based chemotherapy.

Adult↗

PubMed2003

P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens.

BACKGROUND: The prognostic and predictive value of cell cycle regulatory proteins in ovarian cancer has not been established. We evaluated the clinical and biological significance of P21(WAF1), P27(KIP1), C-MYC, TP53 and Ki67 expressions in ovarian cancer patients. MATERIALS AND METHODS: Immunohistochemical analysis was performed on 204 ovarian carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IV treated with platinum-based chemotherapy. Multivariate analysis with Cox and logistic regression models was performed in the whole group, and in the TP53-negative and TP53-positive subgroups. RESULTS: High P21(WAF1) labeling index (LI) was an independent positive predictor of platinum-sensitive response (P = 0.02). Overall survival was positively influenced by P21(WAF1) LI (P = 0.02) or by P21(WAF1) plus P27(KIP1) LI (P = 0.004) in the TP53-negative group only. Ki67 LI showed borderline association with disease-free survival (P = 0.05). Growth fraction was negatively associated with P21(WAF1) and P27(KIP1) indices in the TP53-negative group (P = 0.023 and 0.008, respectively), and these associations were borderline or lost in the TP53-positive group. Endometrioid and clear cell carcinomas differed from other carcinomas by having a low incidence of TP53 accumulation, a high incidence of C-MYC overexpression (70%) and a low median Ki67 LI (all with P <0.001). CONCLUSIONS: We have shown an independent predictive value of P21(WAF1) LI in ovarian carcinoma patients. The prognostic value of P21(WAF1) and P21(WAF1) plus P27(KIP1) LI was determined by TP53 status. A high frequency of C-MYC overexpression in endometrioid and clear cell carcinomas may suggest its role in the development of these tumor types.

Adult↗

PubMed1999

Tumour cell kinetics as a prognostic factor in squamous cell carcinoma of the cervix treated with radiotherapy.

PURPOSE: Proliferative rate and DNA ploidy status were evaluated by flow cytometry in cervical cancer patients, prior to radiotherapy, to assess their importance as prognostic factors to predict survival rates. MATERIAL AND METHODS: Between 1987 and 1995, a total of 260 patients with squamous cell carcinoma (SCC) of the cervix, FIGO stages IB-IIIB were analysed. Tumour samples were incubated with bromodeoxyuridine (BrdUrd) in vitro to measure their total labelling index (totLI) and LI (totLI for diploid and anLI for aneuploid tumours). Proliferation was also assessed by S-phase fraction (SPF) analysis of the DNA profile. Patients had intracavitary therapy (three applications, each of 16 Gy to point A) and XRT of 40-50 Gy given over 4-5 weeks. RESULTS: The cervical tumours were characterized by a high proliferation rate which varied within each clinical stage of disease. The totLI ranged from 1.1 to 33.1% with median value of 9.6% whilst the LI ranged from 1.1 to 37.1% with a median value of 10.9%. Univariate analysis identified patient's age (cut-offpoint < or = 50&greater; years) and to a lesser extent proliferation (cut-off point, median totLI=9.6%) as significant prognostic factors for 5-year survival. The median survival time for younger patients ( < or = 50 years) with tumours of low proliferation (totLI < or = 9.6%) tumours was 17.5 months compared with 56 months in the faster proliferating tumours (P=0.0354). In the older patient sub-group, proliferation rate had no influence on survival. The median LI value was not a useful parameter in survival. Cox multivariate analysis showed that patient age ( < or = 50 years) and low proliferation of the tumour cells (totLI < or = 9.6) were unfavourable prognostic factors for cervical cancers treated with radiotherapy. DNA ploidy was not significant in this series. CONCLUSIONS: These data suggest that further improvements in therapy might be gained by selection of alternative treatments strategies such as neoadjuvant chemotherapy or radiation sensitizers in younger patients with more slowly proliferating tumours.

Adult↗

PubMed1999

Prognostic significance of pretherapeutic and therapeutic factors in patients with advanced cancer of the uterine cervix treated with radical radiotherapy alone.

The prognostic importance of various pretherapeutic and therapeutic factors was analysed in a group of 413 cervical cancer patients with stage IIB (183 pts) and IIIB (230 pts) treated with radical radiotherapy, which consisted of external irradiation and intracavitary brachytherapy. Univariate analysis of pretherapeutic factors revealed the prognostic significance of patient age, history of abortion, stage, haemoglobin and hematocrit levels. Five-year overall survival rate in stage IIB patients was 51%, in stage IIIB 40% and the respective rates for local control at each stage were 61%, and 46%. Univariate analysis of therapeutic factors showed that survival and local control rates increased with the dose, but a significant difference was found only in the case of a paracentral (point A) dose. In a multivariate analysis only patient age, abortions, and clinical stage appeared to have a significant and independent impact on survival. Linear regression analysis results indicated that prolongation of treatment time between 33 and 108 days caused a loss of local control of 0.36% per day.

Adult↗

PubMed1997

Whole abdominal external beam radiation in the treatment of primary carcinoma of the fallopian tube.

Thirty-two patients with adenocarcinoma of the fallopian tube, treated between 1975 and 1990, were studied. Thirteen patients had stage I disease, 9 stage II, and 10 stage III. All patients underwent bilateral salpingo-oophorectomy, total abdominal hysterectomy, and subcolic omentectomy. All patients received postoperative primary whole abdominal external beam radiotherapy. Seventeen patients (53.1%) of the treated group survived NED for at least 5 years. Survival was 76.9% for stage I, 55.6% for stage II, and 20% for stage III. In the Cox multivariate analysis, two variables were independently related to survival: stage of disease and size of residual disease after surgery. Postoperative teleradiotherapy was totally ineffective in gross residual (>2 cm in diameter) disease (0% 5-year NED survivors) and not effective enough in small residual disease (<2 cm in diameter) (33% 5-year NED survivors). Despite postoperative whole abdominal external beam radiotherapy, 3 patients with microscopic, 4 with small, and 4 with gross residual disease did fail within the peritoneal cavity.

Abdomen↗

PubMed1997

Pure immature teratoma of the ovary: analysis of 22 cases.

Between 1970 and 1991, 22 patients with pure immature teratoma were treated at the Center of Oncology in Krakow. Sixteen (72.7%) patients had stage I, four (18.2%) stage II, and two (9.1%) stage III of disease, nine (40.9%) patients had grade 1, 11 (50%) grade 2, and two (9.1%) grade 3 tumors. Eight stage Ia, grade 1 patients were treated with surgery only, the remaining 14 (63.6%) received postoperative chemotherapy. Five-year NED (no evidence of disease) survival was achieved in 81.8% of patients. Out of 16 stage I patients, 15 (93.8%) survived 5-year NED, out of six stage II and III, three (50%) patients only survived this period. We cured all grade 1 patients, and 81.8% (9/11) grade 2; two grade 3 patients died because of tumors. We also cured all six stage Ia patients, treated with unilateral salpingo-oophorectomy (with or without chemotherapy), and all eight stage Ia grade 1 patients treated with surgery only.

Adolescent↗

PubMed1996

Primary invasive vaginal carcinoma treated with radiotherapy: analysis of prognostic factors.

Between 1965 and 1988, 125 patients with primary invasive vaginal carcinoma were treated with radiation therapy at the Center of Oncology in Kraków. Twenty-two superficial stage I patients received radium or cesium intracavitary radiation alone. The remaining 11 patients with stage I disease whose lesions were either large or thick and 77 patients with stages II and III were treated with a combination of external irradiation followed by intracavitary brachytherapy. Fifteen patients with stage IVA received external irradiation only. Five-year NED survival was achieved in 42.4% of patients. In the Cox multivariate analysis three variable were independently related to beneficial survival: grade G1 + G2, stage I + II, and age below 60 years. Of 66 patients who died of vaginal cancer, locoregional failure was found in 51 (77.3%), locoregional and distant in 5 (7.6%), and distant only in 10 (15.1%) patients. Late radiation morbidity occurred in 16 (12.8%) patients.

Adult↗

PubMed1996

Argyrophilic nucleolar organizer regions, bromodeoxyuridine labelling index and DNA ploidy in squamous cell carcinoma of the uterine cervix.

There is increasing evidence that rapidly proliferating tumours, i.e. those with a high bromodeoxyuridine labelling index (BrdUrdLI), could benefit from an accelerated course of radiotherapy. Also, DNA ploidy may be a prognostic factor in term of patients survival. Thus, measurements of cell kinetics and DNA ploidy might become part of routine characterization of tumours before treatment. It is supposed, that a simple and cheap argyrophilic nucleolar organizer regions (AgNOR) test reflects the proliferative status of the tumour and correlates with BrdUrdLI. The BrdUrdLI, AgNOR test and DNA ploidy were assessed in 49 squamous cell carcinoma (SCC) of the cervix (stage II B-III B) and 5 normal epithelium. The number of NORs per cell nucleus, the mean AgNOR particle area and the total AgNOR area per cell were evaluated. Significant differences in the proliferative rate were found within the examined groups of tumours assessed by the BrdUrdLI and AgNOR test. The mean BrdUrdLI values were significantly lower in normal than in carcinomatous cells, while for AgNOR values this was true for stage III B only. The mean number of AgNORs and total AgNOR area per cell were not significantly higher at stage III B than at stage II B, respectively. A high DNA aneuploidy was found in the examined tumours: 78% in stage II B and 77% in stage III B of disease. The results of proliferative markers were not significantly different in diploid than in aneuploid tumours. A significant correlation (p < 0.0001) was found between the mean AgNOR values and BrdUrdLI, however the correlation coefficient was poor (r = 0.50). This was due to different fragments of the same tumours used in these tests. Therefore these techniques might be used as independent methods reflecting the proliferative rate of the tumour.

Adult↗

PubMed1996

[Cervix neoplasms in women younger than 36 years of age].

Between 1970 and 1986, 252 women under 36 years of age with cervical carcinoma were treated in the Center of Oncology in Cracow. The five-year disease-free survival for all patients was 52.8%. In the multivariate analysis tumor stage IIB and III and the age under 30 years were adverse prognostic factors.

Adolescent↗

PubMed1996

[Primary fallopian tube carcinoma. Analysis of 32 cases].

A retrospective analysis of 32 patients with primary fallopian tube carcinoma treated at Center of Oncology in Kraków is presented. In all cases therapy consisted of primary total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by adjunctive radiotherapy. Five year without evidence of disease survived 53.1% of the patients. Stage of disease was the only prognostic factor: survival at 5 years was 76.9% for stage Io, 55.6% for stage IIo, and 20% for stage III.

Adult↗

PubMed1995

[Homogeneous dysgerminoma of the ovary. Analysis of 25 cases].

Between 1972 and 1985, 25 patients with ovarian pure dysgerminoma were treated in the Center of Oncology in Cracow. In twenty-two (88%) patients total abdominal hysterectomy with bilateral salpingo-oophorectomy and postoperative radiotherapy was undertaken. Unilateral salpingo-oophorectomy alone was undertaken in 3 patients in stage IA. The five-year disease-free survival for all patients was 84%, for patients in stage IA degrees -- 100% (11/11), I degree -- 94.4% (17/18), II degrees and III degrees -- 57.1% (4/7).

Adolescent↗

PubMed1995

[A case of advanced vulvar cancer treated with combination therapy].

Presented is a patient with advanced vulvar cancer involving the vagina, the perineum and the anus, with metastases to inguinal lymph nodes. The patient received irradiation and next, an artificial sigmoidal anus was made, with simultaneous vulvectomy performed with an electrosurgery. The patient's survival of 3 years and 3 months encourages to consider in such cases an attempt at applying aggressive surgical treatment combined with external radiotherapy.

Carcinoma↗

PubMed1993

Adjuvant progestagen therapy improves survival in patients with endometrial cancer after hysterectomy. Results of one-institutional prospective clinical trial.

A prospective study was conducted to determine the effectiveness of adjuvant hormonotherapy in endometrial cancer after surgery. Two hundred and five patients were randomly assigned to adjuvant progestagen treatment or were given no additional therapy. The follow-up was 5-years. We concluded that there was evidence of gain from adjuvant progestagen therapy in postoperative endometrial cancer. The group of patients who received progestagens had significantly longer survival than the control group without hormonotherapy (Logrank test; P < 0.001).

17 alpha-Hydroxyprogesterone Caproate↗

PubMed1992

[Prognostic factors in patients with ovarian cancer].

350 patients with ovarian cancer were operated and irradiated postoperatively in the Center of Oncology in Kraków. 5-year survival with no recurrence was 41.7% (I.--77.3%, II.--44.1%, III.--7.7%). Stage, histological grade and residual volume tumor appears to be an important prognostic factors.

Adult↗