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The article reports on the borderline ovarian neoplasm and its diagnosis and treatment. It mentions that the 5-year survival rate for women with stage-one borderline tumors (BOT) is about 95-97 percent and for 10-year survival is between 70 and 95 percent. It states that standard primary surgery is needed which includes omentectomy, peritoneal washing and multiple biopsies while patients with recurrent disease is recommended for a second cytoreductive surgery.

Objectives. Theaim of this study was to give an overview of the Norwegian population of gestational trophoblastic tumors (GTT), diagnosed during 1968–1997 and treated with chemotherapy at the Norwegian Radium Hospital (NRH), with regard to patient characteristics, treatment, and prognosis.Methods. The cases were grouped according to a modified version of the WHO scoring system. Staging was performed retrospectively according to the systems adopted by FIGO. Survival estimates were calculated by the method described by Kaplan and Meier. Cox regression models were used to find the best classification system with regard to prognosis (disease-free survival).Results. A total of 141 cases, 106 invasive moles (IM) and 35 choriocarcinomas (CC), were diagnosed in Norway and treated with chemotherapy at the NRH in the period 1968–1997. Altogether, 56% of the patients were assigned to the low-risk category, 20% to the medium-risk category, and 15% to the high-risk category. Most cases were classified into the clinical stages I (69%) and III (23%). The overall 5-year survival rate was 96%. A more favorable prognosis was seen in patients diagnosed in the 1980s and 1990s compared with those diagnosed in the 1970s (P = 0.04). Five patients had progressive disease and died from the disease. Nine patients relapsed. The prognosis (disease-free survival) was more favorable for IM compared with CC (P < 0.01). The FIGO classification system seemed to be a better predictor of disease-free survival than the WHO scoring system.Conclusions. This study showed that the prognosis of patients with GTT improved in the 1980s and 1990s in Norway, and that the FIGO system might be the best predictor of disease-free survival. [Copyright &y& Elsevier]

Previous studies have shown that the enzyme-glutamyl transpeptidase (GGT) is essential for the nephrotoxicity of cisplatin. This study was designed to determine whether GGT activity is necessary for the therapeutic effect of the drug. The relationship between GGT expression and clinical response to platinum-based chemotherapy was examined in 41 human germ cell tumours. Sections of formalin-fixed, paraffin-embedded tumours were immunohistochemically stained with an antibody directed against human GGT. There was no expression of GGT in any of the 17 seminomas or four dysgerminomas; whereas, 12/12 ovarian yolk sac tumours and 4/4 embryonal carcinomas of the testis were GGT-positive. In stage I tumours fewer tumour cells expressed GGT than in later stage tumours. In four germ cell tumours of mixed histology, the seminomatous and dysgerminoma areas were GGT-negative while the areas of the tumour with yolk sac or embryonal histology contained GGT-positive tumour cells. The patients with seminomas or dysgerminomas who were treated with cisplatin-based chemotherapy, all had a complete response despite the absence of GGT expression in these tumours. Fifteen of the 16 patients with yolk sac or embryonal carcinomas received cisplatin-based chemotherapy following surgery. Twelve had a complete response, while three failed to respond to platinum-based therapy. There was no correlation between the level of GGT-expression and response to therapy in this group. Three of the four patients with tumours of mixed histology were treated with cisplatin-based therapy, and had a complete response. Therefore, expression of GGT is not necessary for the therapeutic effect of cisplatin in germ cell tumours. The results from this study suggest that systemic inhibition of GGT would inhibit the nephrotoxic side-effect of cisplatin without interfering with its activity towards germ cell tumours. [ABSTRACT FROM AUTHOR]

Heat shock protein (HSP) 27, estradiol (ER), progesterone (PR), isocitric dehydrogenase and DNA-ploidy have been measured in 152 endometrial adenocarcinomas. These parameters have also been related to each other and to tumor grade and overall patient survival. HSP27 was assessed immunohistochemically and ploidy by FACS analysis, whilst biochemical methods were used for the other assays. HSP27 was significantly correlated with ER but not PR, grade or ploidy. Both ER and PR were related to tumor grade but not ploidy. Provera (2-14 days, mean 8) had no apparent effect on HSP27 staining but induced isocitric dehydrogenase in 70% of the tumors. Provera decreased ER (64%) and PR (70%) content in originally positive tumors. The presence of either HSP27, ER or PR in the pretreatment sample was significantly associated with provera induction of isocitric dehydrogenase activity; neither tumor grade nor ploidy predicted for induction of this enzyme. High levels of either HSP27, ER, PR or provera-induced isocitric dehydrogenase and diploid DNA were associated with good overall survival, whereas aneuploidy was linked with poor survival. [ABSTRACT FROM AUTHOR]

In a histopathological review of a total population, 1974 cases of endometrial carcinoma were found from 1970 to 1977. Of these 1566 (79.3%) were adenocarcinomas of the endometrioid type, 181 (9.2%) adenoacanthomas, 97 (4.9%) clear cell carcinomas, 74 (3.7%) adenosquamous carcinomas, 31 (1.6%) undifferentiated carcinomas, 22 (1.1%) serous papillary carcinomas and 3 (0.1%) squamous cell carcinomas. Thirty percent of the tumors were well differentiated, 44% moderately and 25.9% poorly differentiated. The mean age at diagnosis was 62.0 years (range 32-93 years). Age was clearly related to histologic type, grade and extent of myometrial infiltration. Crude 5- and 10-year survival rates for the entire group were 73.1 and 61%. For the different subtypes of endometrial carcinoma the 5- and 10-year crude survival rates were as follows: adenoacanthoma 91.2 and 79.6%, adenocarcinoma of the endometrioid type 74.1 and 62.2%, adenosquamous carcinoma 64.9 and 52.7%, undifferentiated carcinoma 58 and 48%, clear cell carcinoma 42.3 and 30.9% and serous papillary carcinoma 27 and 14%. All three patients with squamous cell carcinoma died within a year. The 5- and 10-year survival rates were 87.8 and 79.7% for grade 1 tumors, 76.6 and 62.1% for grade 2, and 60.1 and 48.6% for grade 3. The extent of myometrial infiltration was a string predictor of prognosis. The 5- and 10-year survival rates of patients with intramucosal tumors and tumors infiltrating the inner half of the myometrium were, respectively 89.6 and 82.5%, and 84.7 and 72.7%. Only 48.3 and 29.3% of the patients with tumors reaching the serosa survived, respectively 5 and 10 years. Patients without demonstrable vessel invasion had a significantly better prognosis than those with vessel invasion with a survival rate of 83.5 and 61.1% at 5- and 10-years, compared with 64.5 and 53.8%, respectively. Age at the time of diagnosis was an important prognostic factor for crude survival. Surgico-pathological staging was significantly better than clinical staging in predicting prognosis only in advanced stages. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to describe a new technique of laparoscopic radical hysterectomy without vaginal cuff closure., Methods: Three patients underwent laparoscopic radical hysterectomy, bilateral salpingo-oophorectomy and bilateral pelvic lymph node dissection using an Argon Beam Coagulator. Four trocars were used: umbilical port for the camera, two ports for the operating surgeon and a fourth port for use by the surgical assistant., Results: All patients were clinically staged IB1. Ages were 53, 64 and 58 and BMI was 19.5, 25.2 and 21.4, respectively. Duration of surgery was 375, 325 and 335 minutes, respectively, from first trocar insertion to last closing stitch. Estimated blood loss was 300, 100 and 400 ml and removed pelvic lymph nodes 18, 15 and 26, respectively. The patients tolerated the surgical technique and recovered satisfactorily., Conclusion: These are the first three cases of early-stage cervical carcinoma patients who have been treated with entirely laparoscopic abdominal radical hysterectomy (LARH) and bilateral pelvic lymphadenectomy (BPL) without vaginal cuff closure. To our knowledge, this has not been previously described in the literature. It is feasible and was well tolerated in this small series of patients.

Objective: The aim of this study was to describe the first robotic-assisted radical hysterectomy (Piver type III) and bilateral pelvic lymph node dissection for a patient with Stage Ib1 cervical carcinoma., Case: A 43-year-old woman G1, P1, previously operated on due to endometriosis with removal of the left ovary and fallopian tube, came under our care. In addition, hysteroscopic myomectomy had been done two years before. Otherwise the patient was healthy. Preoperative conization histology revealed 6 mm of stromal infiltration. The patient was offered the da Vinci robotic Wertheim operation for the first time which was well accepted and she was discharged uneventfully on the 4th day postoperatively. Four months later at a routine check-up we found asymptomatic bilateral lymphocysts but otherwise normal status., Conclusion: It is fully possible to perform Piver type III laparoscopic radical hysterectomy using the da Vinci robotic system and it seems that radical dissection is much more precise than the conventional laparoscopic radical hysterectomy.

Clear-cell carcinoma (CCC) and serous papillary carcinoma of the endometrium (UPSC) are rare subtypes of endometrial carcinoma (10%). The histological diagnosis can be made on the dilation and curettage specimens in both types in a very high percentage of the cases. This is important in the planning of treatment. CCC and UPSC are associated with about 50% of all relapses occurring in endometrial carcinoma, and the 5-year survival rate is, on average, 42% and 27% respectively. Surgico-pathological stage, age, and vessel invasion are independent prognostic factors for both groups. The recurrence rate is extremely high, and the most frequent extra-pelvic sites of relapse are the upper abdomen, lungs and liver. Stage Ia patients treated with complete surgical staging alone have a low risk of relapse and need not be offered adjuvant systemic therapy or pelvic radiation. The treatment of patients with CCC and UPSC stage Ib, Ic, II and III should include radical debulking surgery and some form of adjuvant therapy, but it is not clear which type is most effective. Adjuvant pelvic radiotherapy plus intracavitary radiotherapy is usually given in early-stage disease and pelvic radio therapy/or whole abdomen irradiation plus adjuvant systemic chemotherapy (PAC) in advanced disease. However, we are urgently waiting for a large prospective randomized study to compare both modalities. Paclitaxel, alone or in combination, is currently being tested in phase II studies., (Copyright 2001 Harcourt Publishers Ltd.)

Fibroblast growth factor receptor 3 (FGFR3) seems to play an inhibitory role in bone development, as activating mutations in the gene underlie disorders such as achondroplasia and thanatophoric dysplasia. Findings from multiple myeloma (MM) indicate that FGFR3 also can act as an oncogene, and mutation of codon 249 in the fibroblast growth factor receptor 3 (FGFR3) gene was recently detected in 3/12 primary cervical carcinomas. We have analysed 91 cervical carcinomas for this specific S249C mutation using amplification created restriction site methodology (ACRS), and detected no mutations. Immunohistochemistry was performed on 73 of the tumours. Reduced protein staining was seen in 43 (58.8%) samples. Six of the tumours (8.2%) revealed increased protein staining compared with normal cervical tissue. These patients had a better prognosis than those with reduced or normal levels, although not statistically significant. This report weakens the hypothesis of FGFR3 as an oncogene of importance in cervical carcinomas.

Background: The objective of the current study was to increase insight into the biology of fallopian tube carcinoma through an analysis of possible clinical and pathologic determinants of prognosis and to formulate recommendations with regard to a more optimal therapeutic approach for patients with this rare disease., Methods: A study was performed of the pathology specimens and clinical case records from 151 patients with fallopian tube carcinoma who were treated consecutively. Both univariate and multivariate analyses of possible prognostic factors were performed for the whole group and for the subgroup of 41 patients with Stage I disease. The possible significance of serum CA-125 levels as a tumor marker and a marker of response to platinum-containing chemotherapy was evaluated., Results: In multivariate analysis, disease stage, the presence of residual tumor, and a hydrosalpinx-like appearance of the fallopian tube were of independent prognostic significance for the whole cohort. For patients with Stage I disease, the depth of infiltration in the tubal wall and intraoperative tumor rupture were of independent prognostic significance. The marked tendency of this disease for extraperitoneal spread, even in apparently early stages, was confirmed. In 37 evaluable, platinum-naïve patients, an overall response rate of 70% was obtained with platinum-based chemotherapy, with a median response duration of 12.5 months. In view of its low efficacy and high rate of serious complications, the use of postoperative radiotherapy in the treatment of patients with fallopian tube carcinoma is no longer recommended. Serum CA-125 level measurements in fallopian tube carcinoma patients have the same significance as tumor and surrogate markers of response as in ovarian carcinoma patients., Conclusions: Prognostic factors in patients with early stage (Stages 0 and I) fallopian tube carcinoma seem to differ from those in patients with early stage ovarian carcinoma. For patients with more advanced stage disease, due to the striking similarities in prognostic and clinical characteristics between the two diseases, the authors recommend that the treatment and follow-up strategies for patients with ovarian carcinoma be adopted in the management of patients with fallopian tube carcinoma., (Copyright 2000 American Cancer Society.)

Chromosome arm 3p is re-arranged in many tumor types, including cervical carcinomas. Putative tumor-suppressor genes on 3p have been proposed, including the FHIT gene, which maps to chromosome band 3p14.2. We have analyzed 79 primary cervical carcinomas for allelic imbalance (AI) at 17 chromosome 3 loci, including 3 within the FHIT gene. Expression of the FHIT gene was evaluated after immunohistochemistry with an antibody against the pFHIT protein. Previously determined human papillomavirus status, defined after in situ hybridization, showed type 16 or 18 in 56/77 tumors. Tumors were also analyzed for AI at loci within the RB1 (chromosome band 13q14.2) and the TP53 (17p13) genes for AI. AI was found at 1 or more 3p loci in 50/79 tumors, at frequencies ranging from 30% to 52% at the individual loci. Two smallest regions of overlapping deletion (SROs) were found, 1 including parts of the FHIT gene (SRO flanked by D3S1481 and D3S1313) and another more distal SRO between D3S32 and D3S1286. FHIT protein expression was reduced in 57/69 (83%) tumors but not associated with AI at FHIT loci (p = 0.56). AI was found in TP53 and RB1 in 18% and 29% of the samples, respectively. Relapse-free survival was associated with AI in the TP53 gene in both a univariate (p = 0.0003) and a multivariate (p = 0.004) analysis. This study confirms a high frequency of AI at chromosome arm 3p in primary cervical carcinomas. The AI results and the reduced FHIT protein staining indicate that FHIT alterations are important in cervical carcinogenesis., (Copyright 2000 Wiley-Liss, Inc.)

Background: The effect of histopathologic review and subclassification on incidence rates for nonsquamous cell carcinoma (non-SCC) of the uterine cervix in the Norwegian population was evaluated., Methods: All non-SCC from three 5-year periods (1966-70, 1976-80, and 1986-90) were reviewed, classified, and graded., Results: Incidence rates were 1.2, 1.2, and 1.7 per 100,000 for adenocarcinoma and 0.1, 0.3, and 0.5 per 100,000 for other carcinomas in the three periods. Adenocarcinomas increased in all age groups, most markedly in women younger than 35 years. Incidence rates for both major subgroups of endocervical (EC) and endometrioid (EM) carcinomas increased for women younger than 55 years. After 1976-80, the incidence rate for EC, but not for EM, decreased in women older than 55 years. Endometrioid carcinoma became the dominant histologic subtype in 1986-90. Shifts toward lower clinical stages and younger age were found for EC, EM, and carcinoma not otherwise specified (NOS). Patients with NOS, clear cell, serous, or glassy cell/undifferentiated carcinoma were older, and their disease was diagnosed at higher stages. Distribution of International Federation of Gynecology and Obstetrics (FIGO) stages was: Stage I: 62%; Stage II: 21%; Stage III: 12%; and Stage IV: 5%. Distribution of histologic subgroups was: EC:, 24%; EM: 21%; NOS: 16%; clear cell: 7%; adenosquamous: 7%; small cell: 6%; serous: 4%; undifferentiated: 3%; and villoglandular carcinoma: 2%. Other subgroups were seen only sporadically., Conclusions: Incidence rates of non-SCC of the uterine cervix are increasing in Norway. Improvements in diagnostic procedures may explain shifts toward lower stage and age of patients but not the observed differences between histologic subgroups., (Copyright 2000 American Cancer Society.)

Background: The article gives an overview of the telepathology activity at the Norwegian Radium Hospital from the service was launched in 1994 and up until today. We show the development during these years and discuss telepathology in general terms. We also discuss those aspects that determine how well a telepathology service functions., Material and Methods: 74 frozen section slides were diagnosed by two different telepathology systems. One of these systems was used for examining its appropriateness as a tool for second opinion in pathology. A new Internet-based system was developed that provided additional functionality., Results: A telepathology system with a digital camera outperforms one with an analog camera with respect to diagnostic accuracy., Interpretation: Image quality determines the precision of a telepathology service. Telepathology is a feasible tool for second opinion in pathology.

Malignant ovarian germ cell tumors (OGCTs) include immature teratomas (ITs), dysgerminomas (DGs), endodermal sinus tumors (ESTs), choriocarcinomas, and embryonal carcinomas. Knowledge about the genetic changes associated with malignant OGCT development is sparse. We therefore analyzed 25 OGCTs (12 DGs, 4 ESTs, and 9 ITs) for gains and losses by comparative genomic hybridization. In total, more gains than losses were observed, and the number of alterations ranged from 0-20 per tumor. The average number of changes among DGs, ESTs, and ITs was 10, 6, and 1.4, respectively. The most common changes in DGs were gains from chromosome arms 1p (33%), 6p (33%), 12p (67%), 12q (75%), 15q (42%), 20q (50%), 21q (67%), and 22q (58%); gains of the whole of chromosomes 7 (42%), 8 (42%), 17 (42%), and 19 (50%); and losses from 13q (58%). Two of three DGs with a gonadoblastoma component showed gains of 3p21 and loss of 5p, whereas none of the nine pure DGs had these changes, suggesting that they might be characteristic either of gonadoblastoma or of DG developing from a gonadoblastoma. Gain of 12p and gain from 1q were seen in three of four ESTs, whereas gains from 3p, 11q, and Xp and loss from 18q were each found in two tumors. Five of the ITs revealed changes (range, 1-4 changes/tumor), with gains from 1p, 16p, 19, and 22q each being found in two tumors. We conclude that ovarian DGs and ESTs seem to develop via the same genetic pathways that are already known for testicular germ cell tumors. On the other hand, ITs do not exhibit gain of 12p and also typically show fewer changes than other malignant OGCTs, indicating that they arise via different pathogenetic mechanisms.

The prognosis of patients with early stage ovarian borderline tumour and carcinoma is good. In spite of this most patient management has been unnecessarily heavy. DNA ploidy is an independent and the strongest prognostic predictor of survival with an excellent prognosis in patients with diploid tumours, it should be included in the routine evaluation of patients in order to achieve optimal and individual management. Image cytometry is superior to flow cytometry in predicting prognosis.

Objective: The objective of this study was to evaluate the prognostic significance of clinical and histopathologic factors, including a new grading system focusing on the invasive tumor front., Method: A retrospective analysis of 125 surgically treated patients with squamous cell cervical carcinoma FIGO stage IB was conducted. For each tumor, the degree of keratinization, nuclear polymorphism, pattern of invasion, and degree of lymphoid infiltration at the invasive tumor front were graded and given scores between 1 and 4., Results: Clinical tumor size, depth of invasion, and grading of the invasive front had prognostic significance in multivariate analysis, while lymph vascular space involvement, lymph node status, and grade of differentiation did not. Based on clinical tumor size, depth of invasion, and grading of the invasive tumor front, patients could be separated into three groups: One group with minimal risk of recurrence (5-year disease-free survival (DFS) of 100%) consisting of 24% of the patients, an intermediate group with a fairly low risk of recurrence (5-year DFS of about 92%), and a high risk group with a 5-year DFS of 45%. This latter group contained 26% of the patients with 78% of all relapses occurring in the total group of patients. The invasive tumor front grading was reliably reproducible, with inter- and intraobserver agreement of 79 to 87% and kappa values of 0.47 to 0.66., Conclusion: Clinical tumor size, depth of invasion, and grading of the invasive tumor front were the main predictors of prognosis in patients with stage IB squamous cell cancer of the cervix., (Copyright 1999 Academic Press.)

The International Society of Gynecological Pathologists recently agreed on a classification of endometrial hyperplasia into two main groups; hyperplasias with and without atypia. The lesions were further subdivided into simple and complex hyperplasia. These guidelines were subsequently adopted by the World Health Organization. The disease is a result of oestrogen/gestagen imbalance with oestrogen overexpression. The most important prognostic factor is cellular atypia. Progress to invasive cancer is seen in about 20% of the patients with atypical hyperplasia, and most frequently occurs in postmenopausal women. The treatment of endometrial hyperplasia depends on histologic type, patients' age and whether the hyperplasia is a result of endogenous or exogenous oestrogen overexpression. The risk for progression to invasive cancer is minimal in oestrogen treated patients with simple or complex hyperplasia without atypia. Women under 40 years of age in this group can safely be treated with gestagens. In postmenopausal women with simple or complex hyperplasia with atypia, the recommended treatment is surgery including removal of the uterus and the ovaries.

Neoplasms of the vulva and vagina together account for less than 5% of all female genital tract cancers, and very few cases have been analyzed using chromosome banding techniques. We report the karyotypic findings in a consecutive series of ten tumors of the vulva and vagina; in addition to five squamous cell carcinomas of the vulva, we present the first cytogenetic analysis of two malignant melanomas and a Paget disease of the vulva, as well as an adenocarcinoma and a squamous cell hyperplasia of the vagina. Whereas no clonal karyotypic changes were found in the squamous cell hyperplasia of the vagina, the remaining nine malignant tumors showed clonal chromosome abnormalities. An inverse correlation was found between the degree of histologic differentiation and karyotypic complexity in the squamous cell carcinomas of the vulva. The malignant melanomas had chromosomal aberrations that have previously been described in malignant melanomas occurring elsewhere, but were less karyotypically complex. Cytogenetically unrelated clones were detected in the Paget disease of the vulva but not in any of the other tumors; this finding is consonant with the interpretation that at least a proportion of Paget disease of the vulva arises multicentrically within the epidermis from pluripotent stem cells.

Various molecular events of importance in tumour spread, like the gain and loss of adhesion molecules, secretion of proteolytic enzymes, increased cell proliferation, and the initiation of angiogenesis occur at the tumour-host interface (invasive front). We have hypothesised that molecular or morphological characteristics at the invasive front area of various carcinomas may reflect tumour prognosis better than other parts of the tumour. Consequently, we recently developed a simple malignancy grading system restricted to the deep invasive front area of head and neck squamous cell carcinomas. This grading system proved to have additional prognostic value over the established prognostic factors. All similar studies performed so far have confirmed the high prognostic significance of the invasive front grading in squamous cell carcinomas at different locations. In this review paper we describe the system and the hypothesis on which it has been developed. The reproducibility of the grading is acceptable for further extended studies. Interestingly, observations of similar invasive front alterations in different adenocarcinomas suggest that the invasive tumour front may underlie the biological aggressiveness of carcinomas of glandular origin, as well.

Background: The major gene for inherited breast ovarian cancer families shows high penetrance in female carriers. Daughters of living unaffected women in these families are supposed to have a low risk of cancer. Linkage analyses may be used to determine the probability that such families are linked to BRCA1 and, subsequently, to identify mutation carriers in such families. Linkage analyses are dependent upon correct diagnoses of all family members., Methods: We report one breast-ovarian cancer family, prospectively observed, in which a mother and her daughter contracted ovarian and breast cancer almost simultaneously. Linkage analyses indicated that they both had the same BRCA1 mutation. The mother's sister had a possible premalignant lesion at oophorectomy., Discussion: We discuss the problems raised by the pathological classification of possible premalignant lesions, that linkage analyses are sensitive to misclassification of diagnoses, and probability for skipped generation.

Three hundred and seventy-four early-stage ovarian tumours, including 27 borderline tumours and 347 stage I carcinomas, were investigated immunohistochemically for overexpression of the TP53 and MDM2 proteins. TP53 (p53) and MDM2 alterations were detected in 15 and 4 per cent of borderline tumours, and in 50 and 13 per cent of stage I carcinomas, respectively. Mutations in the TP53 gene (exons 5-8) were demonstrated in 29 of the 50 stage I carcinomas studied, using denaturing gel electrophoresis followed by direct sequencing. TP53 overexpression was seen less often in tumours of mucinous and endometrioid type than in tumours of other histological types and more often in moderately and poorly differentiated than in well differentiated tumours. MDM2 protein overexpression was seen more often in clear cell carcinoma than in tumours of other histological types. These results indicate that TP53 abnormalities play a crucial role, and MDM2 abnormalities a minor role, in the development of early-stage ovarian carcinoma. There was no significant association between TP53 or MDM2 alterations and survival in multivariate analysis.

When ovarian cancer is detected at an early stage, prognosis is good, which has led to discussion of a screening programme. The aim of this study was to identify and examine women at high risk of familial ovarian cancer, and to evaluate the inclusion criteria and the diagnostic methods for early detection of ovarian cancer. We report the first round screening findings in a prospective study of 180 women (mean age 43.4 years) considered to be at high risk of ovarian cancer based on family history. They were subjected to gynaecological examination with transvaginal ultrasound (TVU), CA125 and breast examination. Of these, 13 women with oestrogen receptor positive breast cancer had therapeutic oophorectomy and the ovaries were histologically examined. Among 180 women examined, nine ovarian cancers (among them two found at oophorectomy because of breast cancer) (mean age 49.0 years), seven benign tumours of the ovary (mean age 48.1 years), one cancer of the cervix, and four breast cancers were diagnosed. The prevalence of ovarian cancers (5%) was significantly more than in any previous series. TVU as a diagnostic method proved useful and detected 7/9 cancers, whereas CA125 was elevated in 4/9 cancers. To our knowledge, this is the first programme which has successfully delineated a high risk group and prospectively demonstrated their high prevalence of ovarian cancer. Possible biases are discussed.

Background: This study evaluated the prognostic significance of immunohistochemical staining for cathepsin D, epidermal growth factor receptor (EGFR), and c-erbB-2 in patients with early cervical squamous cell carcinoma., Methods: This retrospective analysis comprised 132 patients, all subjected to radical hysterectomy with bilateral pelvic lymphadenectomy for International Federation of Gynecology and Obstetrics (FIGO) Stage IB cervical squamous cell carcinoma. Immunohistochemical staining was correlated with various histopathologic and morphologic characteristics (i.e., tumor size, grade of differentiation, vessel invasion, invasion into parametria, and lymph node metastasis) and relapse free survival., Results: Positive staining for cathepsin D was observed in 47% of tumors, more frequent in tumors giving rise to lymph node metastases. The relapse free survival was lower for patients with cathepsin D positive tumors. Overexpression of EGFR was observed in 25.8% of the tumors. There was no correlation with any of the histopathologic variables investigated. Relapse free survival was lower for patients with tumors overexpressing EGFR. Immunohistochemical staining for c-erbB-2 was observed in 12.1% of tumors with no correlation with relapse free survival. In multivariate analysis, immunostaining of cathepsin D and EGFR obtained independent prognostic significance, and considered together (both negative, one positive, or both positive) was the strongest prognostic factor after tumor size., Conclusions: Immunohistochemical staining for cathepsin D and EGFR is useful as a tool for evaluation of tumor aggressiveness in patients with early cervical squamous cell carcinoma.

The prognostic significance of the detection of HPV (human papilloma virus) DNA in cervical carcinoma was evaluated in 223 cases treated from January 1988 to November 1989. HPV DNA was detected by PCR (polymerase chain reaction) on fresh tumour specimens obtained before therapy was started. HPV DNA of any type was detected in 93.3% of all tumours, HPV16 was the predominant type and was detected in 69% of cases. HPV18 was more frequent in adeno- and adenosquamous carcinoma than in squamous cell carcinoma and occurred more often in poorly differentiated tumours than in more highly differentiated tumours. Patients with HPV negative tumours were on average older than patients with tumours containing HPV. Neither presence of HPV DNA nor HPV type had prognostic significance. In 63 women with early stage tumours submitted to surgery, no difference was found in the frequency of lymph node metastasis, vessel invasion or prognosis related to HPV type. We conclude that neither the presence nor the type of HPV DNA had any prognostic significance in cervical carcinoma.

The objective of this study was to evaluate the prognostic significance of immunohistochemical staining for nm23/nucleoside diphosphate (NDP) kinase in cervical carcinoma. A retrospective analysis of 176 patients with cervical carcinoma FIGO stage IB treated with radical hysterectomy and pelvic lymphadenectomy from 1987 to 1990 was conducted. Immunohistochemical staining using the polyclonal nm23-H1/NDP kinase A antibody was correlated to various histopathological and morphological characteristics (tumor size, histologic type, grade of differentiation, vessel invasion, invasion into parametria, and lymph node metastasis) and relapse-free survival. For controls, sections were obtained from 10 hysterectomy specimens with normal cervical epithelium. Staining for nm23/NDP kinase was observed in 90% of control cases and in 70.5% of cases of cervical carcinoma, more frequent in squamous and adenosquamous cell carcinoma than in adenocarcinoma and more frequent in poorly differentiated than in more highly differentiated tumors. There were no differences related to size of tumor or invasion into vessels or parametria or occurrence of lymph node metastasis. The relapse-free survival was lower for patients with squamous cell and adenosquamous tumors with positive immunostaining for nm23/NDP kinase than for those with negative tumors when evaluated in univariate analysis. In multivariate analysis with tumor size, vessel invasion, invasion into parametria, grade of differentiation, and lymph node metastasis included, this difference was no longer significant. In patients with adenocarcinoma no difference was found. In conclusion, we did not find immunostaining for nm23/NDP kinase to be a useful indicator for prognosis in cancer of the uterine cervix.

Forty-three cases of malignant melanoma of the vulva FIGO stage I, primary treated from 1956 to 1987, have been reviewed. Initial surgery was local excision in 14 patients, vulvectomy in 14, and radical vulvectomy with inguinal lymph node dissection in 15. Recurrent disease was seen in 27 (63%) patients. The 5-year corrected survival was 63%; 10-year survival was 52%. Independent prognostic factors for disease-free and long-term survival were angioinvasion and DNA nondiploidy. Tumor thickness was of prognostic importance in univariate analysis, but did not obtain independent significance. Initial surgical modality did not influence long-term survival, but affected disease-free survival significantly. Local excision carried the greatest risk of local recurrence, but in some of these patients secondary surgery was successful. Because radical surgery did not improve long-term prognosis, wider local excision or vulvectomy seems to be the recommended surgical approach.

In a prospective study of 465 patients with invasive carcinoma of the uterine cervix, the prognostic impact of flow cytometric parameters (ploidy level and fraction of S-phase cells) and clinical variables was evaluated. Median follow-up time was 57 (32-80) months. A total of 230 patients died of cervical cancer during follow-up. Ploidy level had no prognostic significance, neither when analyzed as diploid against nondiploid nor when utilizing different cutoff levels for DNA index (1.3, 1.5, and 1.7). The fraction of S-phase cells (SPF) could be evaluated in 91% of the diploid cases but in only 22% of nondiploid cases. SPF had no prognostic impact. In multivariate analysis, FIGO stage was the only independent prognostic factor (P < 0.001). There was no difference between squamous cell, adeno, and adenosquamous carcinomas. A radical hysterectomy with pelvic lymphadenectomy was performed in 123 cases in stage I-IIA. In this subgroup, tumor size (P = 0.001), infiltration into the parametria (P = 0.005), vessel invasion (P = 0.008), and metastasis to the common iliac nodes (P = 0.013) obtained independent statistical significance in multivariate analysis, while ploidy level had no significance. Neither DNA ploidy nor S-phase analyses should be used in treatment planning.