Correction to: Development of a new reproductive tissue cryopreservation clinical service for children: the Oxford programme.

In the published version, the Acknowledgements section was missing a funding note of co-author Dr C Verrill. The corrected version should read as follows.

Development of a new reproductive tissue cryopreservation clinical service for children: the Oxford programme.

PURPOSE: This article describes the development of a new reproductive tissue cryopreservation clinical service for children at high risk of infertility in the NHS during times of severe financial constraints in the health service. METHOD: A development plan with two phases was drawn up. Phase 1 restricted the service to childhood cancer patients referred to the Oxford Paediatric Oncology and Haematology Principle Treatment Centre. It was estimated that there would be 10 patients/year and used existing staff and facilities from paediatric oncology, surgery, anaesthetics radiology, pathology, psychology, teenage-young adult gynaecology, and an existing Human Tissue Authority tissue bank with a licence for storage of tissue under a Human Sector Licence. Phase 2 extended the service to include children and young adults across England, Wales and Ireland-patients from Scotland having access to a research programme in Edinburgh. The main challenge in phase 2 being resources and the need for patients to be able to be treated as close to home as safely as possible. RESULTS: The Oxford team developed information resources and eligibility criteria based on published best practice, referral and treatment pathways, multidisciplinary team meetings, a network of third party sites, and a dedicated case management and database. As the programme expanded, the Oxford team was able to justify to management the need for a dedicated theatre list. Patient feedback through questionnaires, qualitative work conducted as part of a Ph.D. thesis as well as direct patient stories and interviews in TV, and radio features underpins the positive impact the programme has on patients and their families. CONCLUSION: The Oxford Reproductive Cryopreservation programme delivers fertility preservation treatment to children and young adults at high risk of infertility safely, effectively and as close to home as possible. The onward view is to apply for national funding for this programme for recognition and sustainability.

The pathology clinic - pathologists should see patients.

This invited review describes why and how a pathologist should talk to patients in order to enhance the patient care pathway. The pathologist-patient interaction should become a natural extension to multidisciplinary team decision making, and also become the forum in which patients are helped to understand important aspects of their conditions and the pathological basis for their treatment plans. There is a vast amount of information available through the internet and to digest this can be a difficult process for a patient who is already having to cope with a medical condition. The pathologist is often best placed to sieve through this information and offer the patient the relevant detail necessary to understand the condition and the management pathway. Pathologists can provide up-to-date, simple information about malignant and even certain significant benign conditions, and they can do this with the help of several pictorial tools. In this way, the pathologist becomes an even more active member of a clinical team and helps both clinicians and patients to deal with illnesses in a novel way hitherto not considered.

Genital verrucous carcinoma is associated with lichen sclerosus: a retrospective study and review of the literature.

BACKGROUND: The association of lichen sclerosus (LS) with genital squamous cell carcinoma is well recognized. However, the relationship between LS and verrucous carcinoma remains unclear. OBJECTIVE: To evaluate the associations of genital and perianal verrucous carcinomas with LS. METHODS: We conducted a retrospective study on patients with a genital or perianal verrucous carcinoma and reviewed their histopathology specimens and clinical notes. We also conducted a literature review. RESULTS: We identified a total of 13 patients (including 6 women and 7 men) with a genital or perianal verrucous carcinoma. All 5 women with vulval verrucous carcinoma had coexisting LS (5/5), and 1 man with penile verrucous carcinoma had coexisting LS (1/3). In contrast, no coexisting LS was found in all 5 cases of perianal verrucous carcinoma (0/5). Half of the cases of verrucous carcinoma with coexisting LS had recurrences (3/6), while no recurrences were found in those without coexisting LS (0/7). CONCLUSIONS: Our study and review of the literature demonstrate that vulval verrucous carcinoma is strongly associated with LS. In contrast, perianal verrucous carcinoma is not associated with LS. When genital verrucous carcinoma is diagnosed, it is important to consider LS as a potential concomitant diagnosis and offer appropriate treatments and close follow-up to detect recurrence of verrucous carcinoma.

Why remove all cervical polyps and examine them histologically?

A retrospective analysis of 1366 cervical polyps showed that none had malignant features and 67% were removed from asymptomatic women. A policy removing only cervical polyps from symptomatic women or those with abnormal cervical cytology and limiting histological examination to these polyps would result in significant savings and reduce the small risk of morbidity associated with polypectomy.

Cystic struma ovarii presenting as pseudo-Meigs' syndrome with elevated CA125 levels. A case report and review of the literature.

Struma ovarii is a rare ovarian teratoma consisted predominantly of mature thyroid tissue. Although the vast majority of strumas are benign, they can present mimicking malignancy. We report a case of a postmenopausal woman who presented with a large pelvic mass, ascites, and high CA125 levels. Further investigation confirmed the existence of bilateral pleural effusions. The patient underwent laparotomy, and histology revealed a benign struma ovarii. Twelve months after the removal of the tumor, the patient remained disease free, with no clinical or radiologic evidence of effusion, and normal CA125 levels. This is only the fifth case in the English literature of a benign struma ovarii presenting as pseudo-Meigs' syndrome with elevated CA125. Struma ovarii should be included in the differential diagnosis of a pelvic mass that presents with ascites, hydrothorax, and elevated tumor markers.

Endometrial atypical hyperplasia and subsequent diagnosis of endometrial cancer: a retrospective audit and literature review.

This study investigates the rate of endometrial carcinoma found at hysterectomy in women with a biopsy diagnosis of atypical endometrial hyperplasia, in the John Radcliffe Hospital, Oxford. The Gynecologic Oncology Group (GOG) recently reported a rate of 42.6% in a large prospective study in the USA (Trimble et al. 2006). This retrospective study has identified a similar rate of 45.9% at the John Radcliffe. There is much interest in conservative therapies for atypical endometrial hyperplasia, but with such a high incidence of endometrial carcinoma in cases of atypical endometrial hyperplasia diagnosed by endometrial biopsy, it would seem prudent to exercise caution when considering any conservative therapy.

Mice deleted for cell division cycle 73 gene develop parathyroid and uterine tumours: model for the hyperparathyroidism-jaw tumour syndrome.

The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disorder characterized by occurrence of parathyroid tumours, often atypical adenomas and carcinomas, ossifying jaw fibromas, renal tumours and uterine benign and malignant neoplasms. HPT-JT is caused by mutations of the cell division cycle 73 (CDC73) gene, located on chromosome 1q31.2 and encodes a 531 amino acid protein, parafibromin. To facilitate in vivo studies of Cdc73 in tumourigenesis we generated conventional (Cdc73+/-) and conditional parathyroid-specific (Cdc73+/L/PTH-Cre and Cdc73L/L/PTH-Cre) mouse models. Mice were aged to 18-21 months and studied for survival, tumour development and proliferation, and serum biochemistry, and compared to age-matched wild-type (Cdc73+/+ and Cdc73+/+/PTH-Cre) littermates. Survival of Cdc73+/- mice, when compared to Cdc73+/+ mice was reduced (Cdc73+/-=80%; Cdc73+/+=90% at 18 months of age, P<0.05). Cdc73+/-, Cdc73+/L/PTH-Cre and Cdc73L/L/PTH-Cre mice developed parathyroid tumours, which had nuclear pleomorphism, fibrous septation and increased galectin-3 expression, consistent with atypical parathyroid adenomas, from 9 months of age. Parathyroid tumours in Cdc73+/-, Cdc73+/L/PTH-Cre and Cdc73L/L/PTH-Cre mice had significantly increased proliferation, with rates >fourfold higher than that in parathyroid glands of wild-type littermates (P<0.0001). Cdc73+/-, Cdc73+/L/PTH-Cre and Cdc73L/L/PTH-Cre mice had higher mean serum calcium concentrations than wild-type littermates, and Cdc73+/- mice also had increased mean serum parathyroid hormone (PTH) concentrations. Parathyroid tumour development, and elevations in serum calcium and PTH, were similar in males and females. Cdc73+/- mice did not develop bone or renal tumours but female Cdc73+/- mice, at 18 months of age, had uterine neoplasms comprising squamous metaplasia, adenofibroma and adenomyoma. Uterine neoplasms, myometria and jaw bones of Cdc73+/- mice had increased proliferation rates that were 2-fold higher than in Cdc73+/+ mice (P<0.05). Thus, our studies, which have established mouse models for parathyroid tumours and uterine neoplasms that develop in the HPT-JT syndrome, provide in vivo models for future studies of these tumours.

Overexpression of H-Ryk in mouse fibroblasts confers transforming ability in vitro and in vivo: correlation with up-regulation in epithelial ovarian cancer.

Abnormalities in the function of receptor tyrosine kinases (RTKs) have been demonstrated to be important in the pathogenesis of cancer. H-Ryk, a new member of the RTK family, is an unusual RTK in that it is catalytically inactive because of amino acid substitutions of conserved residues in the catalytic domain. We show by immunohistochemistry that it is expressed in the epithelium, stroma, and blood vessels of normal tissues. Evaluation of a panel of 33 primary ovarian tumors (2 benign, 8 borderline, and 23 malignant) was performed. H-Ryk was overexpressed in borderline and malignant ovarian tumors. In serous and clear cell subtypes, there was increased expression in the epithelium, stroma, and blood vessels. Consistent with this observation, overexpression of H-Ryk in the mouse fibroblast cell line NIH3T3 induces anchorage-independent growth and tumorigenicity in nude mice. This implies that overexpression of the receptor can be transforming and may therefore be significant in the pathogenesis of ovarian cancer.

PCR display identifies tamoxifen induction of the novel angiogenic factor adrenomedullin by a non estrogenic mechanism in the human endometrium.

Tamoxifen is currently the most widely used drug for the treatment of breast cancer, but there now exists considerable evidence that tamoxifen can also induce endometrial hyperplasia in pre menopausal women. We have used PCR differential display on primary human endometrial isolates in an attempt to identify genes induced by tamoxifen but not estrogen. Eight such differentially expressed bands were cloned and sequenced, one of which was found to be the peptide adrenomedullin. We have shown that adrenomedullin is a novel growth factor for endothelial cells and is angiogenic in vivo in the chick chorioallantoic membrane assay. Immunohistochemical analysis of endometrial sections have shown that while macrophages in the endometrium express adrenomedullin at a low level, endometrial macrophages of women receiving tamoxifen strongly express adrenomedullin (P=0.008). We postulate that endometrial induction of the angiogenic factor adrenomedullin by tamoxifen is part of the mechanism by which tamoxifen results in endometrial hyperplasia.

Overexpression of H-Ryk in epithelial ovarian cancer: prognostic significance of receptor expression.

H-Ryk is an atypical receptor tyrosine kinase that is expressed in a differentiation-specific manner in epithelial tissues. We have previously shown by in situ hybridization and immunohistochemistry that H-Ryk is overexpressed in malignant ovarian tumors. In addition, we have demonstrated that overexpression of H-Ryk is transforming in vitro and in vivo. To evaluate whether expression of H-Ryk is a prognostic factor in epithelial ovarian cancer, we carried out a retrospective study of 88 primary malignant ovarian tumors (28 serous tumors, 11 mucinous tumors, 29 endometrioid tumors, 13 clear cell tumors, 3 malignant mixed Mullerian tumors, 1 mixed epithelial tumor, 1 primary peritoneal tumor, 1 undifferentiated tumor, and 1 transitional carcinoma) diagnosed between 1990 and 1993 using immunohistochemistry. On univariate analysis, overall survival decreased significantly with age (P = 0.01); in patients with International Federation of Gynecology and Obstetrics (FIGO) stage II (P = 0.008), FIGO stage III (P < 0.001), and FIGO stage IV (P < 0.001) disease; and in patients with residual disease (residual disease < or = 2 cm, P = 0.007; residual disease > 2 cm, P < 0.001) after surgery. In addition, overexpression of the H-Ryk receptor in malignant epithelium (P = 0.04) and blood vessel (P = 0.01) was associated with a significantly decreased overall survival. H-Ryk blood vessel overexpression (P = 0.03), residual disease > 2 cm (P = 0.006), and residual disease < or = 2 cm (P = 0.01) conferred a significantly shorter progression-free survival. No correlation was found between H-Ryk overexpression and age, histological subtype, degree of differentiation, FIGO stage, or residual disease. Overall, after adjustment for all of the prognostic factors by multivariate analysis (Cox proportional hazards model), residual disease was the most powerful prognostic indicator for overall survival (P < 0.001) and progression-free survival (P = 0.01) in this patient subset. This implies that H-Ryk acts cooperatively with other biological factors in the pathogenesis of ovarian cancer.

Expression of the hypoxically regulated angiogenic factor adrenomedullin correlates with uterine leiomyoma vascular density.

Uterine leiomyomas are the most prevalent benign tumor type in women of reproductive age and are one of the most common indications for hysterectomy. The expression of five angiogenic factors, adrenomedullin (ADM), vascular endothelial growth factor (VEGF), acidic fibroblast growth factor, basic fibroblast growth factor, and platelet-derived endothelial cell growth factor/thymidine phosphorylase, were examined in 91 uteri collected throughout the menstrual cycle; 52 of which contained leiomyomata, and the remainder were normal controls. The microvascular density and endothelial proliferative indices were then determined for each of the uterine sections. ADM and VEGF were the most widely expressed angiogenic factors in the leiomyomas. Furthermore, the expression of ADM and VEGF in the endometrium and myometrium was up-regulated in leiomyoma-bearing uteri compared with controls. Although acidic fibroblast growth factor and basic fibroblast growth factor were expressed in leiomyomas and endometrium in all of the uterine samples examined, they were only expressed in the myometrium of leiomyomata-bearing uteri. Endothelial proliferation in leiomyomas was statistically greater than that of the myometrium and endometrium, both within and between uteri (P < 0.05). The vascular density in the myometrium but not the endometrium was significantly increased in leiomyoma-containing uteri (P < 0.05). Expression of ADM alone correlated directly with vascular density and endothelial cell proliferation index in leiomyomas and myometrium and may account for the high vascularity found in leiomyomas and the myometrium of leiomyoma-bearing uteri. As such, ADM is identified as a novel target for antiangiogenic therapy of these benign, clinically problematic uterine tumors.

Inhibition of leukotriene B4 synthesis does not prevent development of acute renal failure following storage and transplantation.

Compound BW B70C, a selective 5-lipoxygenase inhibitor was tested for its ability to reduce inflammatory damage in an in vivo rabbit model of renal storage and transplantation. Kidneys were stored at 0-2 degrees C for 48 hr prior to autografting. In controls, renal vein LTB4 levels rose significantly after 30 min reperfusion but fell after 2 hr to baseline. TxB2 levels remained at baseline for the 6 hr measured. 6-k-PGF1 alpha levels rose significantly after 1 hr of reperfusion and remained elevated thereafter. Histology after 6 hr reperfusion showed moderate-to-severe cortical edema and mild congestion. Infused colloidal carbon was retained in the perivascular area in a narrow band at the corticomedullary junction, indicating a zone of vascular permeability. At 3 days after transplant, kidneys exhibited widespread tubular necrosis and calcification but little inflammation. Serum creatinine and urea peaked between days 3 and 5. 3/6 rabbits showed no symptoms of renal failure after 3 weeks. Pretreatment with BW B70C prevented the increase in LTB4 but had little effect on TxB2 and 6-k-PGF1 alpha levels. Histology showed no amelioration of cortical edema at 6 hr and congestion and hemorrhage were exacerbated. BW B70C had no effect on either colloidal carbon retention or distribution but did significantly reduce tubular necrosis and calcification at day 3. There was very little inflammatory infiltrate. BW B70C treatment did not improve the long-term viability of transplanted kidneys: 2/6 rabbits showed no symptoms of renal failure after 3 weeks. These data indicate that inhibition of LTB4 synthesis by BW B70C does not prevent the development of acute renal failure following 48 hr hypothermic storage and transplantation.

Ultrastructural changes and lipid peroxidation in rat adipomusculocutaneous flap isotransplants after normothermic storage and reperfusion.

Parallel in vivo, histological, and ultrastructural studies were carried out and markers of lipid peroxidation (Schiff's bases [SB] and thiobarbituric-acid-reactive material [TBAR]) were measured in rat adipomusculocutaneous flap isotransplants that had been stored for 0, 2, 4, 6, and 8 hr under normothermic (37 degrees C) conditions and reperfused for specific periods. Flaps stored for 4 hr and treated with intravenous desferrioxamine (DFX) or hypertonic citrate flush (HCA) were also evaluated. In vivo assessment was made after 7 days of reperfusion. Flaps stored for 4 hr eventually exhibited partial necrosis in vivo, and neither DFX or HCA flush increased the area of surviving skin. Electron microscopy revealed extensive storage damage in epidermal, follicle, fat, and smooth muscle cells and in endothelium. HCA significantly preserved fat cells (P = 0.0035) and DFX diminished smooth muscle damage. Reperfusion injury was seen in endothelial cells in the form of swelling that was not prevented by HCA or DFX. Ultrastructural alterations correlated with changes in susceptibility to lipid peroxidation in fat but not in skin. The results of these parallel studies indicate that both free radical-dependent and independent mechanisms operate in ischemia and reperfusion injury in flap tissue and that fat has a greater predisposition to free radical damage than skin.

Effect of mannitol and polyethylene glycol on the action of frusemide during renal storage and transplantation.

Hypoxic injury is a major cause of tubular necrosis in the corticomedullary junction of isolated perfused kidneys, and is ameliorated by inhibitors of active reabsorption, such as frusemide. Our objective was to determine whether frusemide has a similar effect on hypothermically stored transplanted kidneys and whether this effect is modulated by impermeant solutes included in the preservation solution. The effect of frusemide on cytochrome oxidase (cyt aa3) oxidation, renal hemodynamics, and morphology was investigated in the New Zealand White rabbit renal autograft model using near-infrared spectroscopy and light microscopy. A total of 30 kidneys were autografted in six groups. Kidneys were transplanted with or without frusemide either (1) without storage (groups 1 and 2) or after 72 hr of storage in: (2) hypertonic citrate containing mannitol (groups 3 and 4); and (3) hypertonic citrate containing polyethylene glycol (PEG) (groups 5 and 6). In unstored transplanted kidneys, frusemide infusion stimulated a significant (P < 0.05) increase in hemoglobin oxygenation, compared with untreated controls. There was a tendency for cyt aa3 to become reduced, but there were no significant differences between groups 1 and 2. After 72 hr of storage, frusemide infusion stimulated a significant increase in hemoglobin oxygenation in kidneys stored in mannitol (P < 0.005), but there was no significant change in the kidneys stored in PEG. There was a corresponding reduction in cyt aa3 in kidneys stored in mannitol (P < 0.05) but no change in those stored in PEG. These results suggest that frusemide has a significant effect on cortical hemoglobin oxygenation in transplanted kidneys and on active reabsorption in the corticomedullary junction. The selection of impermeant is important and mannitol is significantly superior to PEG in this model.

Hemoglobin oxygenation kinetics and secondary ischemia in renal transplantation.

The significance of poor medullary reperfusion in the etiology of acute tubular necrosis during renal transplantation is poorly understood. Our objective was to determine the kinetics of renal hemoglobin oxygenation using near-infrared spectroscopy during renal transplantation, to provide a framework against which the timing of mitochondrial dysfunction could be considered. New Zealand White rabbit kidneys were flushed with hypertonic citrate solution (0-2 degrees C and autografted immediately (group 1) or stored at 0-2 degrees C for 72 hours before autografting (group 2). Changes in oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) were monitored by near-infrared spectroscopy for 3 hours of reperfusion. Intrarenal perfusion was evaluated separately by barium sulfate angiography. Reperfusion resulted in rapid increases in HbO2 within 1 minute in both groups. Group 1 HbO2 fell sharply to a minimum at 3 minutes but recovered by 20 minutes; group 2 changes were similar, but there was no recovery (P<0.05 by 10 minutes). Hb increased rapidly in both groups upon reperfusion but in group 2 was significantly greater after 10 minutes (P<0.05). Total hemoglobin levels were similar in both groups. Renal hemoglobin saturation was 69% at 1 minute in both groups; there was no significant change in group 1 but a profound desaturation in group 2 to 25% at 10 minute (P<0.005) and no recovery thereafter. Barium sulfate distribution was normal in all group 1 kidneys; cortical distribution was normal in all group 2 kidneys, but medullary perfusion was poor for the first 60 minutes. Renal hemoglobin oxygenation kinetics as determined here do not correlate with the timing of mitochondrial dysfunction previously reported (Thorniley et al., Kidney International, 1994; 45: 1489). We conclude that secondary ischemia during reflow is not the only mechanism leading to acute tubular necrosis.

Ebselen. Antioxidant capacity in renal preservation.

Ebselen (PZ51) was tested for its ability to inhibit oxidative membrane damage and improve outcome of rabbit kidneys rendered cold ischaemic for 72 hr. In view of the rapid metabolism of ebselen, the antioxidant capacities of its two principal metabolites were first compared with that of the parent drug in an in vitro hepatic microsomal lipid peroxidation system initiated by NADPH/Fe(3+)-ADP. The potent antioxidant activity of ebselen was confirmed but metabolite I (2-glucuronylselenobenzanilide) exhibited no antioxidant potential up to a concentration of 50 microM; metabolite II (4-hydroxy-2-methyl-selenobenzanilide) did inhibit lipid peroxidation but was about 80 times less effective than the parent compound. The storage of rabbit kidneys in hypertonic citrate solution at 0 degrees for 72 hr of cold ischaemia resulted in greatly increased susceptibility to oxidative membrane damage in both the cortex and medulla as determined by the subsequent in vitro formation of two markers of lipid peroxidation (Schiff's bases and thiobarbituric acid-reactive material). Inclusion of ebselen (50 microM) in the flush and storage solution led to a highly significant reduction in these oxidative markers in both regions of the kidney. Intracellular and interstitial oedema was noted in organs subjected to 72 hr cold ischaemia and was reduced by ebselen (50 microM in the flush/storage solution). The rate of post-ischaemic lipid peroxidation was found to correlate well with the extent of oedema in the renal medulla (r = 0.84, P less than 0.001) but no such correlation was found in the cortex. Administration of ebselen (5.5 mg/kg i.v. and 100 microM in the flush/storage solution) did not improve the long-term survival of rabbits following autotransplantation of a single kidney stored for 48 or 72 hr. No protective effect of ebselen could be demonstrated either in terms of graded physiological function or histological outcome.

Reduplication cyst of appendix with mucinous carcinoma and Müllerian metaplasia: a case report.

This report describes a case of mucinous carcinoma and Müllerian metaplasia arising within an appendiceal duplication cyst found incidentally during an emergency Caesarian section. Intestinal duplication cysts are rare and although there are occasional reports of malignant transformation, this is the first case where Müllerian metaplasia was found concurrently with a malignancy. There was no previous history of endometriosis and no other abnormalities were found at surgery. Treatment included surgical excision. The patient is alive and well two years after removal of the cyst.

The effects of the levonorgestrel intrauterine system (Mirena coil) on endometrial morphology.

AIMS: The Mirena coil is a levonorgestrel releasing intrauterine device that is in widespread use. This study aims to document the endometrial morphology associated with this device. METHODS: Endometrial specimens from 75 women with the Mirena coil were reviewed and the histological features detailed. RESULTS: Morphological features found in most of the endometria were decidualisation of stroma (72 of 75 cases), atrophy of endometrial glands (65 of 75 cases), a surface papillary pattern (38 of 75 cases), and a stromal inflammatory cell infiltrate (59 of 75 cases). Additional common histological features were the presence of foci of stromal myxoid change (29 of 75 cases) and stromal haemosiderin pigment (24 of 75 cases). Reactive atypia of surface glands, glandular metaplastic changes, stromal necrosis, and stromal calcifications were found in small numbers of cases. CONCLUSION: The endometrial features are characteristic and relatively constant and are in keeping with the effects of both a progestogenic compound and a mechanical device. Pathologists should be aware of these histological features because the Mirena coil is in widespread use.

Telomerase activity in human gynaecological malignancies.

AIM: To evaluate whether increased telomerase activity can be clinically useful for detecting malignant cells in a variety of gynaecological specimens. METHODS: Telomerase activity was examined in frozen tissue samples of histologically confirmed lesions of the endometrium, ovary, and cervix. It was also assessed in exfoliated cells in cervical smears from patients with premalignant and malignant lesions and in ascitic fluid obtained from cases with malignant or non-malignant ovarian tumours. RESULTS: Solid tissues from carcinomas were telomerase positive in all specimens of endometrial (6/6) and cervical (6/6) origin, and in almost all from the ovary (12/13). Normal tissues from the cervix (0/5) and the ovary (0/5) were telomerase negative, but samples from normal endometrium were found to show telomerase activity, possibly due to the cyclical regenerative nature of this tissue. Conversely, dissociated cells in cervical smears from preneoplastic and frankly neoplastic lesions rarely showed detectable telomerase activity. Thus smears from patients with malignant tumours were only positive in one of two patients, whereas those from CIN-2 (0/5) and CIN-3 (1/17) lesions and from normal (0/10) samples were almost all negative. Telomerase activity was also scarcely detectable in cells obtained from ascitic fluid from patients with ovarian tumours. CONCLUSIONS: As in many other organs, telomerase activity is increased in solid tissue specimens from malignant tumours of the female reproductive tract, but it is not yet a reliable indicator of the presence of exfoliated cancerous or precancerous cells in clinical specimens from such lesions. Interpretation should be guarded until more extensive studies have been conducted. The data on solid tissues presented here confirm that activation of this enzyme is a major hallmark of the neoplastic process.