Loss of heterozygosity at BRCA1/2 loci in hereditary and sporadic ovarian cancers.

Loss of heterozygosity at BRCA1/2 loci in breast and ovarian tumors is a suggested risk factor for germline BRCA1/2 mutation status. We evaluated the presence of losses of selected microsatellite markers localized on chromosomes 17 and 13q in hereditary and sporadic ovarian tumors. 151 consecutive primary ovarian tumors (including 21 with BRCA1/2 mutations and 130 without the mutations) were screened for loss of heterozygosity at loci on chromosomes 17 and 13q. Losses of heterozygosity of at least one microsatellite marker localized on chromosomes 17 and 13q were revealed in 123 (81.5%) and 104 (68.9%) tumors, respectively. Losses of all informative markers on chromosomes 17 and 13 occurred in 30 (19.9%) and 31 (20.5%) tumors, respectively. There was no difference in the frequency of losses at BRCA1 intragenic markers (D17S855 and D17S1323) between BRCA1-positive and BRCA1-negative patients. The frequency of losses on chromosome 17 was higher in high-grade than in low-grade carcinomas. Loss of heterozygosity on chromosomes 17 and 13q is a frequent phenomenon in both hereditary and sporadic ovarian cancers. The frequency of losses at BRCA1 intragenic markers in the ovarian tumor tissue is not strongly related to the presence of BRCA1 germline mutations.

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.

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.

[Endometrial carcinoma in patients with family history of neoplasms]. / Rak blony sluzowej trzonu macicy u chorych z obciazonym nowotworowo wywiadem rodzinnym.

OBJECTIVES: The aim of the study was multifactorial clinical analysis of patients with neoplasmatic family history operated because of endometrial carcinoma in 2nd Dept. of Obstetrics and Gynecology Medical University of Gdansk between 1983-1997. MATERIAL AND METHODS: The group of 117 women who answered inquiry forms was analysed. The other data was obtained from case histories. The subgroup of patients with neoplasmatic family history was selected. RESULTS: The subgroup of patients with neoplasmatic family history was 41.9% of all treated women (49 women). The median age was 58.8; most of them were para- and postmenopausal women. In the group of patients with adenocarcinoma of endometrium the neoplasmatic family history was obtained twice more often then in group with adenosquamous carcinoma. The neoplasmatic disease was found in different members of family (parents, sisters, brothers, grandparents, uncles, aunties and other). In 1/3 cases a neoplasmatic disease was found in few members of the family. CONCLUSION: Women with neoplasmatic family history have to be controlled more strictly because of "coexisted" genetic, internal and economic factors.

[Evaluation of risk factors after intraperitoneal chemotherapy in patients with ovarian cancer]. / Ocena czynników rokowniczych w leczeniu dootrzewnowym chorych na raka jajnika.

DESIGN: The authors sought to evaluate risk factors of patients with ovarian cancer treated with intraperitoneal cisplatin based chemotherapy (IPC). MATERIAL AND METHODS: From January 1996 to December 1998, 24 patients with recurrent or persistent ovarian cancer were treated. We divide them in two groups first beneath 65 year old (19 patients), second above 65 year (5 patients), and in three groups with residual microscopic diseases, residual below 0.5 cm, and between 0.5 and 2 cm in the time of the beginning of treatment with IPC. We also estimate stage (FIGO) as a risk factor. RESULTS: In the first group the study showed (CRP) among 9 patients (SD) among 2 patients PD in among patients. In the second group CRP were observed among 2 patients PD among 2 patients, and SD 1 patient. CONCLUSION: IPC is the valuable method of second line chemotherapy for ovarian cancer. Age is not a risk factor in IPC. IPC prolongs survival in ovarian cancer patients, progression free survival, and gives only slightly adverse effects.

[A rare case of non-Hodgkin's lymphoma of the uterine cervix]. / Rzadki przypadek chloniaka zlosliwego szyjki macicy.

We report a rare case of primary extranodal non-Hodgkin lymphoma of the uterine cervix. A 58-year old, postmenopausal multipara was admitted to the hospital with metrorrhagia and vaginal discharge. After diagnostic biopsy, the patient underwent radical abdominal hysterectomy, bilateral salpigo-oophorectomy and pelvic lymph node dissection. histologically, the lymphoma was classified as non-Hodgkin lymphoma of intermediate malignancy. Immunohistochemical studies revealed that the atypical lymphoid cells were B-cells (CD 20+), indicating that the lymphoma was of B-lineage. Postoperatively, she received adjuvant chemiotherapy. Our experience and a review of current literature are presented.

[Estimation of HPV infection presence in cytological smears in a group of asymptomatic women]. / Ocena wystepowania infekcji HPV w badaniach cytologicznych w grupie pacjentek bezobjawowych.

Papanicolau (Pap) smear is the most important screening method in gynaecological oncology. According to EUROGIN and WHO statements it is suggested to perform additionally molecular detection of human papillomavirus (HPV), which is the most important risk factor of cervical cancer. The aim of this study was to estimate the HPV infection prevalence in healthy, asymptomatic women. Pap smears from 255 women were investigated according to The Bethesda Terminology. HPV DNA was detected by PCR method. We were able to detect high "oncogenic risk" HPV types: 16, 18, 31, 33, 35, 39, 45, 52b, 58 and "low oncogenic risk"--HPV6 and 11. We found only 15 cases (5.9%) of HPV DNA presence. Most of them were HPV16--in 5 patients (33.3%) and HPV58--in 3 (20%). HPV detection could be very useful supplement to Pap smears. It allows selecting the patients with high risk of cervical cancer many years before clinical manifestation of the disease.

Factors influencing period of time between negative second-look laparotomy and ovarian carcinoma recurrence. Multicenter study in Poland.

OBJECTIVE: The aim of our study was to evaluate factors such as primary clinical stage, presence of ascites, serum CA 125 antigen level, histological type of ovarian cancer, cell differentiation and number of chemotherapy cycles influencing the time of recurrence after negative second-look operations. MATERIAL AND METHODS: Having observed complete clinical remission in 356 patients with ovarian cancer, second-look laparotomy was performed. In 180 patients complete pathologic remission was detected and in 73 recurrence was observed. Correlation analysis between time of recurrence and the above-mentioned prognostic factors was carried out by means of the Mann-Whitney and Kruskal-Wallis tests. RESULTS: The time from the second-look operation till diagnosis of relapse ranged from 7 to 36 months (average 21 months). The statistical analysis showed a correlation between the presence of ascites, increased serum CA 125 antigen level, the administration of six chemotherapy courses and the time of recurrence. In all those cases relapse occurred earlier than in patients without ascites, with normal CA 125 antigen levels and after ten courses of chemotherapy. CONCLUSION: Our findings suggest that the stage of clinical advancement and histologic grading do not influence the time of recurrence. The presence of ascites, increased serum CA 125 antigen level and the administration of fewer chemotherapy courses (6 versus 10) after primary surgery affects the earlier relapse of disease.

[Analysis of premature twin pregnancies and deliveries]. / Analiza przebiegu ciazy i porodów blizniaczych zakonczonych przedwczesnie.

Preterm labor is the most frequent complication of twin gestation. Between 1988-1998, 123 twin pregnancies complicated by preterm labor were observed. Complications during pregnancy, mode of delivery, neonatal outcomes, mortality and morbidity were presented. We compared our outcomes to data from current literature.

Sertoli cell tumor in androgen insensitivity syndrome--a case report.

A 26-year-old individual with androgen insensitivity syndrome was operated on for a 3200-g Sertoli cell tumor of the left gonad with retroperitoneal metastases. Six courses of bleomycin, etoposide, and cisplatin chemotherapy followed surgical treatment. Eighteen months after the initial surgery the patient is free of disease and in good health. The association of Sertoli cell tumor with androgen insensitivity syndrome is discussed and the relevant literature is briefly reviewed.

[The correlation between clinical and histological features and complexity of chromosomal changes in primary ovarian cancer]. / Ocena zaleznosci pomiedzy zlozonoscia aberracji chromosomowych guzów pierwotnych a czynnikami klinicznymi i histopatologicznymi raka jajnika.

The aim of the study was to determine the correlation between the complexity of chromosome aberrations in ovarian cancer and its clinical stage and histological grade. 38 primary ovarian cancer tumors were analysed cytogenetically. The chromosomes were obtained from primary cell cultures in vitro and were stained using GTW technique. Advanced clinical stage correlated with complex chromosomal rearrangements. Similarly, histologically poorly differentiated tumors more often displayed complex chromosomal rearrangements (p = 0.004). Simple chromosome aberrations or normal karyotype were more frequently detected in well-differentiated tumors. The analysis of the results revealed that the increase in histological grade and clinical stage correlates with the increase in the number and complexity of chromosomal rearrangements.

[The role of cytogenetic studies in prognosis of treatment results in patients with ovarian cancer]. / Rola badan cytogenetycznych w prognozowaniu wyników leczenia chorych na raka jajnika.

UNLABELLED: The aim of this study was to determine the correlation between chromosome aberrations complexity in carcinomatous cells and survival in 38 patients with ovarian cancer. The material of cytogenic studies were 38 specimens taken from primary neoplastic ovarian tumors, which were than crumbled enzymatically. The suspension of neoplastic cells was used to set up primary cell culture in vitro. Only numerical aberrations or one of structural aberrations were assumed to be simple aberrations. More than one of numerical aberrations or structural aberrations were thought to form complex aberrations. The curve of survival in patients were determined using nonparametrical method of Kaplan and Meier and the differences between the curves were compared using logrank test. CONCLUSIONS: 1. The existence of complex chromosome aberrations in ovarian cancer cells is unfavourable prognostic factor. 2. The cytogenic analysis of neoplastic ovarian tumors together with numerous clinical and histological factors is an important prognostic factor.

[Aggressive clinical behavior of ovarian tumor of low malignant potential: a case report]. / Nowotwór jajnika o granicznej zlosliwosci o bardzo agresywnym przebiegu klinicznym--opis przypadku.

We report a case of ovarian tumor of low malignant potential with very aggressive clinical behaviour reminded of invasive carcinoma and very advanced stage. The patient was dead in short term after radical operation although ovarian tumors of low malignant potential have excellent prognosis.

Cytogenetics of uterine sarcomas: presentation of eight new cases and review of the literature.

Tissue from 14 uterine tumor samples from eight patients-four with endometrial stromal sarcoma (ESS), two with leiomyosarcoma (ULMS), and two with malignant mixed mesodermal tumor (MMMT)-were investigated cytogenetically after short-term culturing. Clonal chromosome aberrations were found in 12 tumors. One ESS showed a recombination between 7p14 and 17q12, a rearrangement characterizing a subset of ESSs. In our series, chromosomes 1, 6, 7, and 16 were involved in structural aberrations most frequently (four cases each). Net loss of 6q material was found in four cases and bands 11q13, 16q13, and 22q13 were each rearranged in four cases. Among 43 uterine sarcomas, including 12 MMTs, now available for evaluation, some differences in breakpoint distribution among different tumor types were found. Rearrangements of bands 1p32, 3p24, and 10q22 were found exclusively in ULMS, whereas aberrations of bands 6p21, 7p21, and 17q12 were found predominantly in ESS.

[A clinical analysis of risk factors in women operated because of endometrial cancer]. / Analiza czynników ryzyka u pacjentek operowanych z powodu raka blony sluzowej trzonu macicy.

OBJECTIVES: The aim of the study was a clinical analysis of risk factors of endometrial cancer such as diabetes mellitus, hypertension, obesitas, using oral contraceptives, smoking cigarettes and neoplasm diseases in a family. MATERIAL AND METHODS: Between 1983-1997, 336 patients was operated in 2nd Department of Obstetrics and Gynaecology Medical University of Gdansk because of endometrial cancer. 117 women, who answered inquiry form questions was selected. RESULTS: The median age of patients was 58.9 years (41 to 83 years). In 71.79% the neoplasm disease was found in postmenopausal age. Nulliparas was 16.2%. In 96 cases (82.5%) an adenocarcinoma was found, in 14 cases (12.0%)--a adenosquamous cell carcinoma and in 1 case (0.8%)--a squamous cell carcinoma of uterine corpus was found. In 51 patients (43.6%) a obesitas was found, in 44 patients (43.6%)--hypertension and in 14 patients (11.9%)--diabetes mellitus. In 11 cases (9.4%) diabetes mellitus and hypertension coexist and in 9 cases (7.7%)--all diseases. Only 2 women (1.7%) used oral contraceptives, so it is impossible to estimate its influence on risk of endometrial cancer. 18 patients (15.4%) was smokers and 49 women (41.9%) had a neoplasm diseases in their families (the most often--43.7%--a neoplasm disease was in families of women with adenocarcinoma). CONCLUSIONS: The percentage of nulliparas was lower then it is described in literature (40-50%) and was 16.2%. The highest percentage of nulliparas was found in a group of women with adenosquamous carcinoma. The most often histological type of endometrial carcinoma was high-differentiated adenocarcinoma.

[A complementary treatment of patients with endometrial carcinoma after surgical treatment]. / Leczenie uzupelniajace chorych operowanych z powodu raka trzonu macicy.

OBJECTIVES: The different methods of a complementary treatment used in a group of 117 patients, aged 41 to 83, after surgical treatment because of endometrial cancer in 2nd Department of Obstetrics and Gynaecology Medical University of Gdansk between 1983-1997, were analysed. RESULTS: The hysterectomy with removal of uterine adnexa was performed in all cases, in 18 patients supplemented by pelvical lymphadenectomy. The median age of women was 58.9 years. In 96 cases (82.5%) an adenocarcinoma was found, in 14 cases (12.0%)--a adenosquamous cell carcinoma and in 1 case (0.8%)--a squamous cell carcinoma of uterine corpus was found. In 52 patients (44.4%) a complementary treatment was used: in 43 patients (82.7%)--radiotherapy, in 4 patients (7.7%)--chemiotherapy, in 5 patients (9.6%)--radio- and chemiotherapy and in 1 case (1.9%)--radio- and hormonotherapy. In 8 women (6.8%) a second laparotomy was made but only in 1 case it was caused by ileus because of neoplasm metastases. The median survival of all patients was 6.1 years; without complementary treatment--6.48 years, after radiotherapy--6.25 years, after chemiotherapy--2.75 years and in a group of women after associated treatment--4.4 years. CONCLUSIONS: Between all patients with endometrial cancer after complementary treatment, the longest survival was found in a group of women after complemetary radiotherapy then in a group of patients after chemiotherapy or associated treatment (radio- and chemiotherapy). The highest percentage of women without any symptoms of disease was in a group of patients after radio- and chemiotherapy or only chemiotherapy against to patients after chemiotherapy.

[Evaluation of the course of pregnancy and the newborn state in women with bronchial asthma]. / Ocena przebiegu ciazy oraz stanu noworodka u kobiet chorujacych na dychawice oskrzelowa.

The course of pregnancy and the condition of newborn babies were studied in 18 women who suffer from severe bronchial asthma, intensified during the time of pregnancy, and 20 with a mild course of the same disease. The danger of intrauterine hypotrophia of the fetus was proved in women with the active bronchial asthma. Additional studies showed that the more serious the case was, the bigger decrease of the value of estrogen and placental lactogen was. Because of the possibility of sudden deterioration of a patient's condition, detailed assessment in necessary in all women with bronchial asthma.

[Complete heart block treated with electrotherapy in a 30-year-old pregnant women with Kearns-Sayre syndrome]. / Blok calkowity serca wymagajacy elektroterapii u 30-letniej ciezarnej z zespolem Kearns-Sayre.

Kearns-Sayre syndrome (KSS) is a form of mitochondrial myopathy in which specific clinical features, namely progressive external ophthalmoplegia, pigmentary retinal degeneration and onset before age 20 occur. It can also be associated with cardiac conduction defects, neurological and variety of endocrine and metabolic disorders. Recognition of mtDNA deletion as the genetic basis of KSS has confirmed the validity of clinical criteria. The purpose of the report is to describe a 30-year-old woman presenting typical clinical features of KSS. On muscle biopsy ragged red fibres and mitochondrial abnormalities on electron microscopy were seen. In spite of menstrual disturbances she became pregnant and delivered health child. In 30 week of pregnancy the VVI pacemaker was implanted because of syncope most probably related to paroxysmal complete heart block.

[Carcinoid syndrome in a pregnant woman. Case report]. / Zespól rakowiaka u ciezarnej. Opis przypadku.

The carcinoid syndrome was discussed based on the reference materials. The aim of the work is to present the course of pregnancy ended by the delivery of a full-term healthy child by a 32-year-old multipara with the carcinoid syndrome diagnosed 3 years earlier.

Trisomy 12 and 4 in a thecoma of the ovary.

Cytogenetic analysis of short-term tissue culture from a thecoma of the ovary demonstrated the presence of trisomies of chromosomes 12 and 4 in all analyzed cells. Our finding confirms the consistency with which trisomy 12 is observed in benign sex cord/stromal tumors and suggests that trisomy 4 may be a second event in tumorigenesis of thecoma.