[Cervical cancer screening: past--present--future]. / Zervixkarzinom-Screening: Gestern--heute--morgen.

Despite the undisputed and impressive success which has been achieved since the 1960s by cervical cytology in the fight against cervical cancer and its precursor stages, during which the mortality rate in industrialized countries over the last 40 years has been reduced by two-thirds to three-quarters, a perfect and error-free screening procedure is still a long way off and will probably never be reached. There are two main reasons for this, the lack of adequate coverage and suboptimal quality and assessment of smears. Two screening procedures are in use Europe, an opportunistic and an organized system. Both systems have many advantages but also disadvantages. In organized programs the coverage is higher (up to 80%), although similar numbers are also achieved by non-organized programs over a 3-year cycle, even if they cannot be so exactly documented. The decision on which system is used depends on the health system of the country, public or non-public, and many other national circumstances. However, in both systems prerequisites for a satisfactory result is a high quality in the sampling technique, the processing and the assessment. Therefore, several guidelines have been introduced by state and medical societies for internal and external quality assurance. New technologies, such as thin-layer cytology or automation for replacement or support of conventional cytology liquid-based cytology proved not to be superior enough to justify the high costs of these systems. The recognition of the strong causal relationship between persistent infection with high-risk human papillomavirus (HPV) types and cervical cancer and its precursors has resulted in the development of comparably simple tests. Primary screening using HPV typing alone is not recommended in opportunistic screening due to the low specificity but high sensitivity because it leads to many clinically irrelevant results which place women under stress. In organized screening HPV testing is always and only possible in combination with cytology. Various models and approaches are in the testing phase and appear promising. HPV testing is on the other hand well accepted and recommended as a triage test to select women with equivocal smear results (Pap group III, ASCUS) if a biopsy is required or can be followed up and also for follow-up of patients after cone biopsy. However, vaccination of young girls against oncogenic HPV types which has now become widespread still leaves many questions open for the future because the observation period is too short. There is justified hope that this will become a valuable tool in cervical cancer control and may lead to a substantial reduction in the burden of cervical cancer in the future. However, as the current vaccines on the market do not cover all oncogenic virus types and the effects of vaccination will only be observed after many years, the necessity of a cytological screening will remain unrestricted. Therefore, cervical cytology will remain as the trusted, simple to use, economic and proven, like no other method for early cancer detection, efficient procedure even in the foreseeable future. If carried out with the highest quality demands it will play a central role in the early detection of cervical cancer.

[Reevaluation of cytological smears in patients with cervical cancer. Regional quality assurance program with the cooperation of the Austrian Society for Cytology, the Carinthian Medical Association and the Carinthian Ministry of Health]. / Reevaluation von Zervixabstrichen bei Zervixkarzinompatientinnen. Regionales Qualitätssicherungsprogramm unter Mitwirkung der Osterreichischen Gesellschaft für Zytologie, der Kärntner Arztekammer und der Landessanitätsdirektion Kärntens.

BACKGROUND AND METHODS: To evaluate the reasons for the occurrence of invasive cervical cancer in Carinthia despite cytological screening, all 132 patients diagnosed with cervical cancer in the years 2000-2002 were recorded and all gynecological cytological smears made within the 5 years prior to the diagnosis of cancer were reevaluated. RESULTS: Within the 5 years prior to diagnosis, no gynaecological cytological smear was found for 50% of the patients diagnosed with cervical cancer in the years 2000-2002. In the year 2002, a total of 53 patients were reported to have cervical cancer and 78 smears were reevaluated. Of all the smears primarily diagnosed as negative, 49% were found to be positive (> or =Pap III) after reevaluation and 92% of all smears "correctly" diagnosed as negative showed quality deficiencies. The interobserver variability (kappa-statistics) showed a moderate value when the primary screening results were compared with the reevaluation. The interobserver variability within the group of reevaluators was also moderate.

Small-cell carcinoma of the uterus and the vagina: experience with ten patients.

BACKGROUND: Small cell carcinomas (small-CCs) of the uterine cervix are rare and highly malignant neoplasms. Patients tend to develop distant metastasis early and thus are potential candidates for systemic therapy. We reviewed the experience with small-CCs of the uterus and vagina at two Austrian University hospitals. MATERIAL AND METHODS: Ten patients (median age, 50 years; range, 18-92) with small-CC of the cervix (n=7), uterine corpus (n=2), and the vagina (n=1) were treated at the two centers between 1988 and 1998. Eight patients underwent radical surgery, 7 of whom also received chemotherapy. Two additional patients underwent primary radiotherapy. RESULTS: All Pap smears were suspicious for cervical malignancy. The median survival was 12 months (range, 6-86) and overall 5-year survival was 10%. Five of 8 surgically treated patients had lymph node involvement (62%). Of the 7 patients with small-CC of the cervix only one, who had FIGO stage IIB disease and positive pelvic nodes, survived long-term (86 months) with no evidence of disease. She had received six courses of dose-intensive platinum chemotherapy after radical surgery. All three patients with small-CC of the uterine corpus or vagina developed recurrence within the first year after diagnosis. Of the 7 patients who received chemotherapy, 5 developed progressive or recurrent disease in the paraaortic region (n=2), peritoneum (n=1), liver (n=1), or pelvis (n=1). CONCLUSION: These results confirm the particularly unfavorable prognosis of patients with small-CC of the genital tract. The optimal treatment for these patients most probably including concurrent chemo-radiotherapy remains to be defined.

Cytopathology in Austria.

Cervical cancer screening developed rapidly during the 1970s. Today, approximately 1.5 million smears are taken annually, so 50% of the target population are screened every year, 30% are cytologically underserved (24% never had a smears, 6% only once). This figure correlates with the fact that there are still 30% deaths from cervical cancer compared with 1960. Since 1998 a voluntary quality assurance programme was introduced by the Austrian Society of Cytology, based on comparison of results reported from participating laboratories.

Cathepsin D in ovarian cancer: prognostic value and correlation with p53 expression and microvessel density.

OBJECTIVE: Overexpression of ubiquitous lysosomal aspartyl protease cathepsin D (CD) is involved in the progression of cancer. This study investigates the prognostic value and the association of cathepsin D expression with clinicopathological parameters, p53 expression, and angiogenesis in ovarian cancer. METHODS: Cathepsin D was determined immunohistochemically in 43 ovarian tumors of low malignant potential (LMP) and 80 invasive tumors FIGO stage I-IV. Results were correlated with clinicopathological characteristics, p53, and microvessel density (MVD). Survival analysis of cathepsin D expression and MVD was performed in invasive tumors. RESULTS: Epithelial tumor cathepsin D expression was more common in LMP tumors (65.1%) compared to invasive tumors (43.7%; P = 0.02). In LMP tumors, stromal cathepsin D was associated with mucinous tumors (P = 0.01), whereas in invasive tumors, epithelial cathepsin D expression was associated with clear cell tumors (P = 0.003). Invasive tumor cathepsin D had a negative relation to p53 expression. In LMP tumors, stromal cathepsin D correlated with microvessel density (P = 0.03). Stromal cathepsin D expression was an independent prognostic factor for disease-free survival (DFS) in patients with invasive cancer (P = 0.03, Cox regression), while cathepsin D expression missed to be of prognostic value for overall survival (OS) in invasive ovarian cancer. MVD had no influence on survival in invasive ovarian cancer (P > 0.05). CONCLUSION: Our study demonstrates a prognostic value of cathepsin D expression in invasive ovarian cancer, while cathepsin D expression in LMP tumors seems to be linked to angiogenesis. The relation among cathepsin D, p53 expression, and angiogenesis demonstrates biological differences between invasive ovarian cancer and LMP tumors.

Immunohistochemical expression of laminin-5 in cervical intraepithelial neoplasia.

OBJECTIVES: Laminin-5 is an attachment protein for epithelial cells. Several studies of a variety of cancers have reported increased expression of laminin-5 in carcinoma in situ and invasive cancer. This study was designed to investigate the correlation between the grade of cervical intraepithelial neoplasia and the immunohistochemical expression of laminin-5 in the cytoplasm and in the basement membrane underlining dysplastic squamous cells. METHODS: We used immunohistochemical methods to stain paraffin-embedded sections of cervical cone biopsies with a monoclonal antibody specifically targeting the 2-chain of human laminin-5 protein. The study sample included 175 slides: 7 normal cervical epithelium, 36 lesions of mild dysplasia, 50 lesions of moderate dysplasia, 81 lesions of severe dysplasia, and 1 invasive squamous cell carcinoma. RESULTS: We found a statistically significant correlation between the grade of cervical intraepithelial neoplasia and laminin-5 immunoreactivity in the cytoplasm (P < 0.01) and in the basement membrane (P = 0.03) by use of the Wilcoxon rank-sum test. CONCLUSIONS: According to previously published reports we confirmed with a higher number of cases a correlation of laminin-5 expression in the cytoplasm and/or basement membrane and grade of dysplastic lesion in the cervical epithelium. This study warrants further investigations with special interest to follow-up to investigate whether laminin-5 is a marker to predict the risk of progression of cervical intraepithelial neoplasia lesions.

Lack of impact of platinum dose intensity on the outcome of ovarian cancer patients. 10-year results of a prospective randomised phase III study comparing carboplatin-cisplatin with cyclophosphamide-cisplatin.

This prospective multicentre phase III trial was conducted to assess whether increased platinum dose intensity (DI) by combining carboplatin with cisplatin has an impact on overall survival (OS) and progression-free interval (PFI) compared with the standard combination of cyclophosphamide and cisplatin in patients with epithelial ovarian cancer. A total of 253 patients with epithelial ovarian cancer of stages International Federation of Gynecology and Obstetrics (FIGO) IC-IV were randomised to receive either cyclophosphamide (600 mg/m(2), intravenously (i.v.), day 1) and cisplatin (100 mg/m(2), i.v., day 2) (n=125) as the standard regimen or carboplatin (300 mg/m(2), i.v., day 1) and cisplatin (100 mg/m(2), i.v., day 2) (n=128), every 28 days for six courses. The median follow-up was 6.0 years. 124 patients randomised to the platinum dose-intensified arm and 123 patients randomised to the standard arm met all of the eligibility criteria. Patient characteristics were well balanced between the two treatment groups. All eligible patients randomised were included in the analysis of OS and PFI. The median OS of the standard and platinum dose-intensified arms were 41.2 (95% Confidence Interval (CI): 29.2-50.7) and 43.0 months (95% CI: 34.3-63.2), respectively (P=Non-significant (N.S.). The median PFI in the standard arm was 29.7 (95% CI: 17.4-41.7) versus 23.1 months (95% CI: 17.8-35.4) in the platinum dose-intensified arm, respectively (P=N.S.). Toxicity, comprising leucopenia, granulocytopenia, thrombocytopenia, anaemia, emesis and nausea, was statistically significantly higher in the platinum dose-intensified arm than in the standard arm. Unexpectedly, no statistically significant differences were found between the 2 arms' overall neuro- and ototoxicity. When converting carboplatin-platinum into cisplatin-platinum on the basis of an equivalence ratio of 4:1, patients in the platinum dose-intensified arm received a total platinum dose 1.58 times the platinum dose of the standard arm. With 35.0 mg/m(2)/week being administered, the total platinum DI of the dose-intensified arm was statistically significantly (P<0.0001) higher than that of the standard regimen (with 22.0 mg/m(2) being administered). Calculating the average administered relative dose intensities of the regimens yielded almost identical results with 0.56 and 0.58 for the standard and experimental arms, respectively. Thus, by conventional means, a 1.6-fold increase in the platinum DI could be reached by combining carboplatin and cisplatin without unacceptable morbidity. Nevertheless, this did not translate into any therapeutic benefit for the patient, even in the optimally debulked group of patients for whom dose-intensification would have been expected to be of benefit.

Is high-risk human papillomavirus infection associated with cervical intraepithelial neoplasia eliminated after conization by large-loop excision of the transformation zone?

OBJECTIVE: To investigate whether high-risk HPV infection associated with cervical intraepithelial neoplasia (CIN) was successfully eliminated after electrosurgical conization by large-loop excision of the transformation zone (LLETZ). STUDY DESIGN: 142 women, who were admitted for conization of CIN 1-3 were recruited into a prospective follow-up study of HPV infection, including cervical sampling for HPV DNA before, and then 3, 6 and 12 months after surgery. We examined whether there were any differences in the rate of HPV DNA positivity after LLETZ between specific risk groups, such as patients with primary (i.e. before surgical treatment) high-risk HPV infection, CIN of different grades, and positive margins. RESULTS: We did not detect statistically significant differences between specific risk groups. According to the assay used (hybrid capture II) at the last follow-up visit 94% of primarily infected patients were completely free from infection with high-risk HPV types, while 6% had persisting HPV infection. CONCLUSIONS: With a detection limit of 5000 genomes/ml HPV DNA the hybrid capture II results revealed, that after electrosurgical removal of CIN in 94% of patients testing positive for high-risk HPV DNA prior to surgery were negative 12 months post-surgery.

Downregulation of KAI1 metastasis suppressor protein is associated with a dismal prognosis in epithelial ovarian cancer.

OBJECTIVES: The aim of this study was to investigate the impact of downregulation of KAI1 metastasis suppressor protein in epithelial ovarian cancer. In addition, correlation of KAI1 and p53 immunostaining was investigated. METHODS: Expression of KAI1 and p53 was immunohistochemically determined in 107 specimens of epithelial ovarian cancer stages I-IV. Survival of patients was investigated using uni- and multivariate analysis. RESULTS: Strong KAI1 expression was observed in 17.8% of cases, moderate in 27.1%, weak in 21.5%, and complete loss of KAI1 expression in 33.6%. Overexpression of p53 protein was observed in 45.8%. There was correlation of KAI1 expression neither with p53 expression nor with various clinical and histopathological parameters. Serous ovarian cancers showed significantly decreased staining intensity of KAI when compared to other histological types (P = 0.007). Univariate and multivariate analysis revealed that patients with strong or moderate expression of KAI1 had a significantly longer overall (P = 0.0013) and disease-free survival (P = 0.0048) when compared to those with low or absent expression. CONCLUSION: KAI1 downregulation is an independent prognostic factor in epithelial ovarian cancer, indicating dismal prognosis. Our study did not reveal a correlation between p53 status and KAI1 expression, suggesting that p53-independent mechanisms might be involved in the downregulation of KAI1.

Prognostic value of beta1-integrin (=CD29) in serous adenocarcinomas of the ovary.

BACKGROUND: Integrins are heterodimeric transmembranous proteins, comprised of two transmembrane subunits, called alpha and beta. They bind to various structures of the extra cellular matrix (ECM) and are responsible for cell-cell interactions. The aim of the current study was to evaluate the prognostic value of beta1-integrin in patients suffering from malignant serous surface epithelial-stromal tumors of the ovary. MATERIALS AND METHODS: With immunohistochemical methods we investigated 76 formalin-fixed, paraffin-embedded tissue samples. FIGO stages I, II, III and IV were present in 18, 10, 41 and 7 cases, respectively. RESULTS: 12 sections (15.8%) stained positive for beta1-integrin (=CD29), 64 sections (84.2%) showed no expression of beta1-integrin. The product limit method by Kaplan and Meier showed no statistical significance of beta1-integrin expression on overall survival, (p = 0.1005, log-rank test). Also the univariate Cox regression analysis showed no statistical significance of beta1-integrin expression on overall survival (p=0.1066), whereas in the multivariate analysis, adjusted for grading, FIGO stage and residual tumor, the expression of beta1-integrin turned out to be significantly correlated with reduced overall survival (p=0.0208). CONCLUSION: Our results using multivariate Cox regression analysis indicated a shorter overall survival for patients with positive staining for beta1-integrin in malignant serous surface epithelial-stromal tumors of the ovary. This pilot study warrants further investigation of the role of beta1-integrin in ovarian cancer.

Leiomyosarcoma of the vulva. A case report.

BACKGROUND: Leiomyosarcoma of the vulva is a rare mesenchymal tumor. Biologic features of a low grade tumor were investigated by an immunohistochemical workup. CASE: A 38-year-old woman presented with a slowly growing vulvar mass. Surgical treatment was performed, and a low grade leiomyosarcoma of the vulva was diagnosed. Immunohistochemical reactions were performed with monoclonal antibodies against desmin, vimentin, smooth muscle actin, cytokeratin, S-100 protein, estrogen, progesterone and androgen receptor, p53 protein, Ki-67 antigen, leukocyte common antigen and polyclonal antibodies to factor VIII-related antigen. Expression of estrogen, progesterone and androgen receptor was present in addition to a moderate number of Ki-67-positive cells and absence of p53 protein overexpression and lymphatic cell infiltration besides adequate microvessel density for smooth muscle tumors. Since the immunohistochemical markers indicated a less aggressive tumor, any further adjuvant therapy was rejected. The patient was without recurrence 24 months later. CONCLUSION: The immunohistologic profile proved the low histologic grade of vulvar leiomyosarcoma. The findings helped to estimate prognosis and plan therapy.

Signal-amplified colorimetric in situ hybridization for assessment of human papillomavirus infection in cervical lesions.

Detection and typing of human papillomavirus (HPV) infection may have a major impact in cervical-screening and follow-up. In this study various commercially available techniques for the detection of HPV were evaluated. HPV-status was determined in 86 samples of cervical cancer by PCR and direct sequencing, catalyzed signal amplified colorimetric DNA in situ hybridization (CSAC- ISH) (GenPoint system, DAKO), immunohistochemistry (IHC) and in 12 selected cases also by conventional, non-amplified ISH. Twenty-one samples of cervical intraepithelial neoplasias grade III (CIN III) were investigated by CSAC-ISH, conventional ISH and by IHC, in corresponding PAP smears HPV-detection and typing was performed by CSAC-ISH and Hybrid Capture test II (HC). In additional 20 PAP smears HPV typing was performed using HC and a novel immunocytochemical system for HPV detection and-typing. CSAC-ISH showed good correlation with PCR analysis in cervical cancers: In 87% of PCR positive cases, HPV infection was also detected by CSAC- ISH (66/76). HPV 16 was detected in 75% of PCR-positive cases (44/59), HPV 18 in 71% of PCR positive cases (5/7). CSAC-ISH detected HPV 31 in only 29% of PCR positive cases (2/7), and HPV 33 in 64% of PCR-positive cases (23/36). Nevertheless, CSAC-ISH- false negative cases for HPV 31 or 33 were nearly always combined infections with other HPV types, which were detectable by CSAC-ISH in most cases. CSAC-ISH revealed HPV infection in 20 of 21 HC-positive cervical smears, while in corresponding biopsies (CIN III) CSAC-ISH detected 100% of HPV infections. Conventional, non-amplified ISH showed significantly lower sensitivity compared with CSAC-ISH, and immunocyto- and -histochemistry were of very low sensitivity for detection of HPV. CSAC-ISH is an easy-to-handle method for detection and typing of cervical HPV infection, and shows sufficient sensitivity for clinical practice.

Expression of hypoxia-inducible factor 1alpha in epithelial ovarian tumors: its impact on prognosis and on response to chemotherapy.

PURPOSE: To investigate the impact of expression of hypoxia-inducible factor (HIF)-1alpha on prognosis and on response to chemotherapy in epithelial ovarian tumors. EXPERIMENTAL DESIGN: Expression of HIF-1alpha protein was studied by immunohistochemistry in 102 specimens of epithelial ovarian cancers, in 50 borderline tumors, and in 20 cystadenomas. Results were correlated with p53, p21, and bcl-2 expression, microvessel density (MVD), apoptotic rate of tumor cells, and survival. RESULTS: In 68.6% of ovarian cancers and 88% of borderline tumors, expression of HIF-1alpha was observed. There was a significant correlation of HIF-1alpha protein expression and MVD (P < 0.001). HIF-1alpha overexpression alone and MVD showed no impact on survival of cancer patients. Furthermore, the response to platinum-based chemotherapy was independent from HIF-1alpha expression. Expression of HIF-1alpha correlated with apoptotic rate in the majority of cases, especially in low malignant potential tumors. In contrast, in cancer patients with strong expression of HIF-1alpha and p53 protein overexpression, not only a significantly increased MVD (P = 0.032, Mann-Whitney test) but also a significantly shorter overall survival was observed (P < 0.0001, Cox regression). The apoptotic rate was very low in these tumors. CONCLUSIONS: HIF-1alpha protein overexpression alone has no impact on the prognosis of ovarian cancer. The combination of HIF-1alpha protein overexpression with nonfunctional p53, however, indicates a dismal prognosis.

Lymphatic microvessel density as a novel prognostic factor in early-stage invasive cervical cancer.

Few data on the influence of lymphatic microvessel density (MVD) on survival in cancer are available since until recently there was no reliable immunohistological marker for lymphatic endothelium. Using an antibody staining podoplanin, a novel marker for lymphatic endothelium, lymphatic MVD in tissue samples of 85 patients with cervical cancer classification pT1b treated by radical hysterectomy was investigated. Survival was determined using univariate and multivariate analyses. Lymphatic MVD was also compared to MVD assessed by immunostaining against factor VIII-related antigen, which is considered a marker for blood vessels. Patients with >5 lymphatic microvessels/0.25 mm(2) field had significantly better overall survival (mean 91.8 months) than those with < or =5 lymphatic microvessels/field in univariate analysis (mean 113 months) (p = 0.0105, log-rank test). In multivariate analysis, lymphatic node involvement (p =0.0183), vessel infiltration (p =0.0158) and lymphatic MVD (p =0.0269) remained independent prognostic factors. No correlation between lymphatic MVD and various clinical and histopathological parameters was observed. Correlation between lymphatic MVD and MVD assessed by immunostaining against factor VIII was only weak (p = 0.004, r = 0.312, Spearman's coefficient of correlation). Our results suggest that increased lymphatic MVD is associated with favorable prognosis in early-stage cervical cancer.

Selective immunohistochemical staining of blood and lymphatic vessels reveals independent prognostic influence of blood and lymphatic vessel invasion in early-stage cervical cancer.

Lymphovascular space invasion was shown to play a key role in the progression of cervical cancer. Because of the absence of a specific marker for lymphatic vessels, earlier studies could not reliably distinguish between blood and lymphatic vessel invasion. By immunostaining for podoplanin, a novel marker for lymphatic endothelium, and for factor VIII-related antigen, we determined lymphatic and blood vessel invasion in tissue samples of 98 patients with cervical cancer pT1b treated by radical hysterectomy. Eleven (11.2%) specimens showed invasion of blood vessels, 20 (20.4%) showed invasion of lymphatic vessels, and 15 (15.3%) showed invasion of blood and lymphatic vessels. There was a strong association of lymphatic vessel invasion and lymph node involvement (P < 0.001). In univariate analysis, both blood and lymphatic vessel invasion failed to reach a statistically significant influence on overall survival, but a significant influence on disease-free survival was found (P = 0.0002 and P < 0.0001, respectively). In multivariate analysis of disease-free survival, only blood vessel invasion remained statistically significant (P = 0.0457). Lymphatic vessel invasion reached significance when lymph node status was excluded from the model (P = 0.0025). Both lymphatic vessel and blood vessel invasion occur frequently in early-stage cervical cancer. Determination of the vessel status may be of clinical importance because it signifies the risk of recurrent disease.

Impact of human papillomavirus infection on the expression of the KAI1 metastasis suppressor protein in invasive cervical cancer.

Downregulation of KAI1 metastasis suppressor protein is associated with dismal prognosis in a variety of cancers. Mutation of p53 was suggested to be involved in KAI1-downregulation. In cervical cancer, p53 is inactivated by human papillomavirus (HPV) oncoprotein E6 with the grade of inactivation depending on the HPV type. KAI1-expression was immunohistochemically determined in 67 specimens of cervical cancer, HPV-typing was performed using polymerase chain reaction (PCR), cloning, and sequencing. KAI1-downregulation was found in 68.1% of patients, HPV-infection in 91%. There was no association of KAI1-downregulation and infection with a particular HPV type. KAI1-downregulation in cervical cancer seems independent of HPV-E6 induced p53 inactivation.

Inflammatory stromal reaction correlates with lymphatic microvessel density in early-stage cervival cancer.

BACKGROUND: In early-stage cervical cancer, high lymphatic microvessel density (LMVD) indicates favorable prognosis. This unexpected finding was thought to be an effect of local immunological response, although no data supported this thesis. MATERIALS AND METHODS: LMVD and lymphovascular invasion (LVI) were assessed in 85 specimens of cervical cancer stage pT1b by immunostaining for podoplanin, a marker for lymphatic endothelia. Local immunological response, evident by inflammatory stromal reaction (ISR), was determined in H&E-stained slides and rated from grade 1 (absent or weak) to 3 (strong) RESULTS: A good correlation of LMVD and ISR was found (p=0.002). While a strong correlation between LMVD and the presence of LVI was found (p<0.001), no association between LMVD and pelvic lymph node involvement (p=0.732) was observed. ISR indicated favourable prognosis of patients (p=0.0247, log-rank test). CONCLUSION: Our findings suggest that ISR might play a role in the induction of lymphangiogenesis in early stage cervical cancer.

Preperitoneal lipoleiomyoma of the abdominal wall in a postmenopausal woman.

OBJECTIVE: Extrauterine leiomyomas are rare events. These tumors may be easily misdiagnosed as ovarian tumors at the clinical investigation. We present the first case of an otherwise healthy postmenopausal woman, hysterectomized 20 years ago, who developed a preperitoneal lipoleimoyoma in the 30-year-old scar of a Pfannenstiel incision. The patient received continuous hormone replacement therapy (HRT) for 5 years with 1.25 mg conjugated estrogen and 5 mg medrogeston per day. METHODS: In sections of the tumor, immunohistochemical reactions with antibodies against actin, desmin, vimentin, estrogen and progesterone receptors and factor VIII related antigen was performed. RESULTS: Histologic findings revealed cellular fascicles of spindle-shaped smooth muscle cells in a whorled arrangement. Mitotic figures were absent. Central degenerative changes and focal edema were observed. Between muscle fascicles, a significant amount of fat cells (20% of tumor volume) was visible. Leiomyocytes showed immunohistochemicaly positive reactions with actin, desmin, vimentin, and steroid hormone receptors. Based on these findings, the tumor was diagnosed as lipoleiomyoma. CONCLUSIONS: Origin of the tumor of smooth muscle cells of vessels located in the abdominal wall and development under influence of oral steroids seems most probable. HRT appears to promote the development of extrauterine leiomyomas in postmenopausal women.

Cervical cancer screening in Austria.

Austria's target population of women aged 20 years and over consists of 3 million people. There is mainly opportunistic screening, except in one county with a target population of 120000, in which organised screening has been practiced for several years. There are approximately 1.5 million smears annually, exclusively taken by gynaecologists. The recommended screening interval is 1 year. The slides are screened by MTs with a maximum workload of 12000 smears annually in 65 laboratories, mainly headed by pathologists. As shown by Vutuc and colleagues (Wien Klin Wochenschr 1999, 111, 354-359) the opportunistic screening system covers 60% of the Austrian target population leaving an unsatisfactorily high rate of underserved, mainly postmenopausal, women. Nevertheless, the cervical cancer mortality rate could have been decreased to one third during the past 40 years.