Early identification of persistent trophoblastic disease with serum hCG concentration ratios.

The objective of the present study was to assess the diagnostic potential of serum human chorionic gonadotropin (hCG) ratios obtained at different intervals after evacuation of hydatidiform mole to diagnose persistent trophoblastic disease (PTD) and to compare its diagnostic accuracy with the current FIGO 2000 criteria as a gold standard. We calculated hCG ratios from serum hCG concentrations of 204 patients (86 with and 118 without PTD) registered with the Dutch Central Registry for Hydatidiform Moles between 1977-2004. The hCG ratios obtained in week 1, 3, and 5 after evacuation identified, respectively, 20%, 52%, and 79% of patients with PTD (median: 3.0 weeks) at the 95% specificity level, while FIGO 2000 criteria identified, respectively, 0%, 16%, and 66% (median: 4.7 weeks). It is concluded that a serum hCG ratio identifies patients with PTD approximately 2 weeks earlier than the internationally accepted FIGO 2000 criteria and identifies more than 75% of patients who develop PTD by the fifth week after evacuation.

[Ovarian tumour in a girl with chronic abdominal pain and distension]. / Ovariumtumor bij een meisje met chronische buikpijn en zwelling van de buik.

A 12-year-old girl presented with chronic abdominal pain and distension that had persisted for 6 and 3 months, respectively. The cause was a Sertoli-Leydig cell tumour originating in the left ovary. The cyst and ovary were resected. The patient recovered and was asymptomatic 2 years after the operation. Ovarian tumours are rarely seen in children. The sex cordstromal tumours constitute a heterogeneous subgroup. Two of the most frequently observed sex cord-stromal tumours are the juvenile granulosa cell tumour and the Sertoli-Leydig cell tumour. Even though these tumours may contain histologically malignant characteristics, their behaviour is usually benign. Clinical characteristics are endocrine symptoms, fatigue, chronic abdominal pain and abdominal distension. In addition, pressure from the tumour mass may result in symptoms in adjacent organ systems. Surgical excision is usually curative. Patients with advanced disease may benefit from adjuvant chemotherapy. Chronic abdominal pain is frequently observed in children and, in some rare cases, may be caused by ovarian tumours.

Malignant peritoneal mesothelioma in a 76-year-old woman with a history of asbestos fiber ingestion.

We report on a woman with malignant mesothelioma of the peritoneum. This is the first report of a subject with this disease who revealed a history of asbestos ingestion by asbestos-contaminated food. She presented with episodes of sweating and fever, ascites, and weight loss. At laparotomy, small tumor deposits were noted on the peritoneum. The omental cake was removed, together with the uterus, ovaries, and tubes which were all macroscopically normal. The diagnosis was established by immunohistochemistry and electron microscopy. Postoperatively, her complaints of fever and sweating disappeared. She refused further chemotherapy. After questioning her for asbestos exposure, she told us that, years ago, she used to prepare vegetables for cooking in rain water collected from a roof made of asbestos.

Coexisting high-grade glandular and squamous cervical lesions and human papillomavirus infections.

The frequency of high-risk human papillomavirus (hr-HPV) genotypes in patients with adenocarcinoma in situ (ACIS) with coexisting cervical intraepithelial neoplasia (CIN), ACIS without coexisting CIN, and high-grade CIN (CIN II/III) was studied, in order to gain more insight into the relation between hr-HPV infections and the development of coexisting squamous and glandular lesions. The SPF(10) LiPA PCR was used to detect simultaneously 25 different HPV genotypes in biopsies obtained from 90 patients with CIN II/III, 47 patients with ACIS without coexisting CIN, and 49 patients with ACIS and coexisting CIN. hr-HPV was detected in 84 patients (93%) with CIN II/III, 38 patients (81%) with ACIS without CIN, and in 47 patients (96%) with ACIS and coexisting CIN. A total of 13 different hr-HPV genotypes were detected in patients with CIN II/III, and only five in patients with ACIS with/without coexisting CIN. HPV 31, multiple hr-HPV genotypes, and HPV genotypes other than 16, 18, and 45 were significantly more often detected in patients with CIN II/III, while HPV 18 was significantly more often detected in patients with ACIS with/without CIN. There were no significant differences in the frequency of specific hr-HPV genotypes between patients with ACIS with or without coexisting CIN. In conclusion, the frequency of specific hr-HPV genotypes is similar for patients with ACIS without CIN and patients with ACIS and coexisting CIN, but is significantly different for patients with CIN II/III without ACIS. These findings suggest that squamous lesions, coexisting with high-grade glandular lesions, are aetiologically different from squamous lesions without coexisting glandular lesions.

The value of loop electrosurgical conization in the treatment of stage IA1 microinvasive carcinoma of the uterine cervix.

The objective of this study is to assess the value of Loop Electrosurgical Conization (LEC) in the treatment of stage IA1 microinvasive squamous cell carcinoma (MIC) of the uterine cervix. Retrospectively, 82 patients with FIGO stage IA1 MIC, primarily treated with LEC on see and treat basis, were analyzed. After the initial LEC, 16 patients received cytologic and colposcopic follow-up only, 66 patients underwent a second procedure (repeat LEC, Cold Knife Conization (CKC), or hysterectomy), and four patients underwent a third procedure (hysterectomy). In 63 patients (77%) no residual CIN 3 or MIC was present after the initial LEC. Treatment of residual CIN 3 or MIC was equally effective with a repeat LEC as with CKC. One patient defaulted follow-up and developed a recurrence in the vaginal vault and was treated with a radical hysterectomy. LEC can be used as an alternative for CKC in treatment of patients with stage IA1 MIC. The advantage of LEC is that it can be performed as an outpatient procedure in addition to a diagnostic colposcopy and does not require a major anesthetic. Only a small number of patients will need a more extensive procedure.

Decreased expression of Ki-67 in atrophic cervical epithelium of post-menopausal women.

Papanicolaou-stained cervical smears (Pap smears) of post-menopausal women often present difficulties in distinguishing atrophic cervical epithelium from high-grade cervical intraepithelial neoplasia (CIN2-3). The aim of this study was to disclose differences in proliferative activity in normal cervical epithelium, cervical atrophy, and high-grade CIN lesions, in order to develop specific and sensitive classifiers to discriminate between cervical atrophy and high-grade CIN, both in cervical smears and in tissue sections. A case-control study was done on 83 patients. Proliferative activity was assessed in histological sections using the monoclonal antibody MIB1. An image analysis system was used to characterize different proliferation-associated features. Preceding Pap smears were restained with MIB1 and proliferative activity was measured by a point-counting procedure, carried out on a training set of 32 cases and a test set of 51 cases. In cervical atrophy, proliferative activity was significantly lower than in normal epithelium (p<0.001). Proliferative activity measured in both biopsies and cervical smears was considerably higher in high-grade CIN than in normal epithelium (p<0.001). Discriminant analyses resulted in four classifiers, based on proliferation parameters, to discriminate between cervical atrophy and high-grade CIN, and between CIN2 and CIN3, in biopsy specimens and cervical smears, respectively. The two classifiers for biopsy specimens resulted in 100% correct classification. Application of the classifier obtained from the training set of Pap smears resulted in 100% correct classification of the Pap smears in the test set. The classifier to discriminate between CIN2 and CIN3 in Pap smears, obtained from 36 patients, resulted in 87% and 90% correct classification, respectively.

Leiomyomatosis peritonealis disseminata: does malignant transformation occur? A literature review.

Leiomyomatosis peritonealis disseminata (LPD) is a rare smooth muscle tumor. In the literature more than 100 cases have been described. LPD is characterized by multiple small nodules on the peritoneal surface, mimicking a malignant process with metastases, but generally demonstrates benign histologic features. Exposure to estrogen seems to play an etiologic role. Many patients have uterine leiomyomas as well. The diagnosis of LPD is easily made on biopsy. Reduction of estrogen exposure is generally sufficient to cause regression of LPD. Surgical castration or gonadotrophin releasing hormone agonists seem good alternatives in the case of progression or recurrence of LPD. In six patients a malignant leiomyosarcoma has been described shortly after the diagnosis of LPD was made. Five of these patients did not have uterine leiomyomas or exposure to exogenous or increased endogenous estrogen. The relationship with pregnancy in the sixth patient may be coincidental. Whether malignant transformation of LPD occurs remains uncertain. Characteristics of these patients differ from those of LPD patients and may indicate a high malignant potential, necessitating a different approach.

Development and validation of a computerized cytomorphometric method to assess the maturation of vaginal epithelial cells.

BACKGROUND: After menopause, declining levels of estrogens may cause vaginal discomfort, or so-called "vaginal atrophy." Evaluation of therapies for vaginal atrophy may be performed using the so-called "maturation index." The maturation index is expressed as the percentage of (para)-basal, intermediate, and superficial epithelial cells in a vaginal smear. Manual assessment of the maturation index is subject to inter- and intraobserver variations. In this study, assessment of the maturation of cells in vaginal smears using automated image analysis was investigated. MATERIALS AND METHODS: Automated assessment, using a commercially available image analysis system, was performed on hematoxylin-eosin-stained cytospin specimens. A training set was constructed by an experienced cytotechnologist, based upon visual classification of stored grey value images. From this, two discriminant functions (DFs) were calculated capable of classifying cells in one of the three types. These cell classifiers were capable of classifying 97% of the cells correctly. Data from automated assessment were compared with those of classical manual counting. Specimens of 13 mature and 6 atrophic vaginal specimens were assessed in duplicate, both manually and by image analysis, using the DFs. RESULTS: No significant interobserver effect was found for image analysis, whereas a significant effect was found for manual counting. Both methods were able to distinguish between matured and atrophic specimens. CONCLUSIONS: It was concluded that for assessment of vaginal maturation, the use of automated image analysis systems is recommended. Besides increased reproducibility, image analysis systems yield additional data describing the size and shape of the cytoplasm and nucleus of cells, which might increase discriminating power.

Dosimetric analysis of chimeric monoclonal antibody cMOv18 IgG in ovarian carcinoma patients after intraperitoneal and intravenous administration.

In this study the potential of intraperitoneal (i.p.) and intravenous (i.v.) administration of chimeric iodine-131-labelled MOv18 IgG for radioimmunotherapy was determined. The dosimetry associated with both routes of administration of cMOv18 IgG was studied in patients. Eight patients suspected of having ovarian carcinoma received 150 MBq 131I-cMOv18 IgG i.p. Blood and urine were collected and serial gamma camera images were acquired. Another group of four patients received 7.5 MBq 131I-cMOv18 IgG i.v. For all patients, tissue biopsies were obtained at surgery. Activity in the blood after i.p. administration was described by a bi-exponential curve with a mean uptake and elimination half-life of 6.9+/-3.2 h and 160+/-45 h, respectively. For i.v. infusion the mean half-life for the elimination phase was 103+/-12 h. Cumulative excretion in the urine was 17%+/-3% ID and 21%+/-7% ID in 96 h for i.p. and i.v. administration, respectively. Scintigraphic images after i.p. administration showed accumulation in ovarian cancer lesions, while all other tissues showed decreasing activity with time. Tumour uptake determined in the ovarian cancer tissue specimens ranged from 3.4% to 12.3% ID/kg for i.p. administration and from 3.6% to 5.4% ID/kg for i.v. administration. Dosimetric analysis of the data indicated that 1.7-4.3 mGy/MBq and 1.7-2.2 mGy/MBq can be guided to solid or ascites cells after i.p. and i.v. administration, respectively. Assuming that an absorbed dose to the bone marrow of 2 Gy will be dose limiting, a total activity of 4.1 GBq 131I-cMOv18 IgG can be administered safely via the i.p. route and 3.5 GBq via the i.v. route. At this maximal tolerated dose, a maximum absorbed dose to 1-g tumours in the peritoneal cavity of 18 and 8 Gy can be reached after i.p. and i.v. administration, respectively. For the i. p. route of administration, dose estimates for the tumour are even higher when the electron dose of the peritoneal activity is also taken into account: total doses to the tumour of 30 Gy and 22 Gy will be absorbed at the tumour surface and at 0.2 mm depth, respectively. In conclusion, therapeutic tumour doses can be achieved with 131I-cMOv18 IgG in patients with intraperitoneal ovarian cancer lesions with no normal organ toxicity. The i.p. route of administration seems to be preferable to i.v. administration.

The role of deoxyribonucleic acid image cytometric and interphase cytogenetic analyses in the differential diagnosis, prognosis, and clinical follow-up of hydatidiform moles. A report from the Central Molar Registration in The Netherlands.

OBJECTIVES: To assess the value of deoxyribonucleic acid ploidy in the differential diagnosis and clinical follow-up of hydatidiform moles, the histopathologic features, deoxyribonucleic acid ploidy, and clinical follow-up were compared in 347 cases: 143 complete moles, 52 partial moles, and 152 abortions, of which 56 cases were hydropic abortions with histologic features of triploidy but lacked trophoblastic hyperplasia. STUDY DESIGN: In all cases deoxyribonucleic acid image cytometry was performed, and in 85 of these cases interphase cytogenetics was also performed. RESULTS: With use of deoxyribonucleic acid image cytometry and interphase cytogenetics, a bimodal polyploid deoxyribonucleic acid pattern was present in 97% of complete moles, 27% of partial moles, and 4% of abortions. All these cases of partial mole were reclassified to complete mole on the basis of this deoxyribonucleic acid pattern and the histopathologic features in spite of the presence of fetal blood cells, amnion, or yolk sac. Deoxyribonucleic acid triploidy was found in 95% of the remaining partial moles, in 77% of hydropic abortions with histologic features of triploidy, and in 14% of the remaining abortions. Reliable differentiation between deoxyribonucleic acid triploid partial moles and hydropic abortions with histologic features of triploidy was not possible on basis of the histopathologic features (trophoblastic hyperplasia) or 3.5c exceeding rates. Deoxyribonucleic acid diploidy was found in 1% of complete moles, 23% of hydropic abortions with features of triploidy, and 78% of the remaining abortions. Deoxyribonucleic acid tetraploidy was rarely found (1% of complete moles, 2% of partial moles, 1% of abortions). Persistent gestational trophoblastic disease developed in 33% of the bimodal deoxyribonucleic acid polyploid cases (all complete moles), in 1% of the diploid cases (concerning one of the two diploid complete moles), and in 1% of the triploid cases (partial moles). CONCLUSION: Deoxyribonucleic acid analysis is essential in the diagnosis of hydatidiform moles to decide on clinical follow-up.

Improvement of clinical staging in cervical cancer with serum squamous cell carcinoma antigen and CA 125 determinations.

Staging of cervical cancer is routinely performed by means of examination under anesthesia in combination with radiographic and/or endoscopic techniques. This "clinical" staging leads to 10-25% misclassification, mostly due to positive lymph nodes or lymph or blood vessel invasion. Determination of pretreatment squamous cell carcinoma antigen (SCC) and CA 125 serum levels may solve part of this staging problem and may improve the selection of the most appropriate individual therapy. Using 2.5 ng/ml (SCC) and 35 U/ml (CA 125) as cutoff levels, we studied 99 patients retrospectively. Elevated levels were found in 27% (SCC) and 23% (CA 125). In clinical stage IB or IIA disease 45/81 patients had positive nodes or lymph or blood vessel invasion at operation. Of these patients 49% had elevated serum levels of SCC or CA 125. Strongest correlation was found with blood vessel invasion (57%). Only 19% of low-stage patients without evidence of vascular spread of disease had positive levels. The positive predictive value of SCC and CA 125 for detection of vascular spread of disease in low-stage cervical cancer was 76%. In most centers surgery is the primary treatment of choice in low-stage cervical cancer. Nevertheless, with respect to patient survival, results of primary surgery and primary radiotherapy are comparable. Radiotherapy given in an adjuvant setting leads to a high incidence of severe complications. In order to overcome part of these complications one should consider radiotherapy as the primary therapy of choice in patients with clinical stage IB or IIA cervical cancer with elevated pretreatment SCC or CA 125 levels.

Persistent gestational trophoblastic disease: DNA image cytometry and interphase cytogenetics have limited predictive value.

DNA flow cytometry has shown a wider spectrum of DNA content in the complete hydatidiform mole (CM) than the originally reported diploidy. Conflicting results have been published about the relationship of DNA content and the occurrence of persistent gestational trophoblastic disease (PGTD). In the present study, 71 cases of CM and 4 cases of partial mole accompanied by PGTD and 100 cases of CM without PGTD were evaluated with DNA image cytometry for differences in DNA-ploidy pattern, expressed as the 2.5c and 5c exceeding rates. A pilot study of 20 cases of each group was performed using interphase cytogenetics to detect differences in the frequency of numerical chromosomal aberrations and in sex chromosome composition. For this purpose, DNA probes specific for the pericentromeric regions of chromosomes 1 and X and for the long arm of chromosome Y were incubated on 6-micron paraffin tissue sections. The results showed no differences between CMs with or without PGTD; DNA polyploidy occurred in 99% and 98% of cases, respectively; the 2.5c exceeding rate and 5c exceeding rate were 62.6 and 62.4, and 6.5 and 6.0, respectively. The frequency of numerical chromosomal aberrations as detected by interphase cytogenetics was 23.4 and 22.8%. An XY pattern was found in 3 of 20 cases of CM with PGTD and in 4 of 20 cases of CM without PGTD. The four cases of partial mole showed a DNA-ploidy pattern identical to that of a CM. For this reason, they would be better reclassified as CMs, despite the presence of nucleated red blood cells or amnion. Although nuclear atypia and corresponding increased DNA content is pronounced but variable in CMs, the occurrence of PGTD is not related to variations in quantitative DNA content nor to gross heterology or homology in sex chromosomes.

Ovarian cancer incidence (1989-1991) and mortality (1954-1993) in The Netherlands.

OBJECTIVE: To examine ovarian cancer incidence and mortality in the Netherlands, and to relate trends in mortality to changes in parity and use of oral contraceptives. METHODS: Age-standardized and age-specific incidence and mortality rates are presented using incidence data from the Netherlands Cancer Registry, 1989-1991, and mortality data from the Netherlands Central Bureau of Statistics, 1954-1993. RESULTS: In the period 1989-1991, age-standardized incidence of ovarian cancer was 14.9 per 10(5) woman-years. The majority (89%) of these tumors had an epithelial origin. Two-thirds of all newly diagnosed ovarian cancers already showed extension to the pelvis or beyond at diagnosis. From the period 1954-1958 to 1969-1973, age-standardized mortality rates increased from 10.6 to 13.1 per 10(5) woman-years. Thereafter, a decline was noted to 11.4 per 10(5) woman-years in the period 1989-1993. Age-specific mortality rates showed a pattern of rising mortality in the elderly, whereas mortality in the younger age categories was declining. The number of live births has declined gradually, and oral contraceptive use has increased. CONCLUSION: Incidence of ovarian cancer is high in the Netherlands, but comparable to other countries in north-western Europe and North America. Mortality rates are rising in the elderly and declining in the young. Further research is needed concerning the effects of oral contraceptives, fertility drugs, and hormone replacement therapy on the incidence and mortality of ovarian cancer.

Pharmacokinetics, biodistribution and biological effects of intravenously administered bispecific monoclonal antibody OC/TR F(ab')2 in ovarian carcinoma patients.

The bispecific monoclonal antibody (biMAb) OC/TR combines the anti-ovarian-cancer reactivity of the MOv18 monoclonal antibody (MAb) with the reactivity of an anti-CD3 MAb. Pre-clinical studies have indicated that this biMAb is able to redirect the cytolytic activity of T cells towards tumour cells, resulting in efficient tumour-cell lysis. To assess the clinical potential of systemic biMAb-based cancer therapy we initiated a study in ovarian-cancer patients. Five patients suspected of ovarian cancer received 123I-OC/TR F(ab')2 i.v. Unexpectedly, the first patient developed side effects (grade III-IV toxicity) starting 30 min after infusion (p.i.) of 1 mg of OC/TR F(ab')2. After approval of the Ethical Committee, the study was continued at lower dose levels (0.1 mg; 0.2 mg). However, at the 0.2-mg dose level similar side effects were observed. FACS analysis indicated that all peripheral T cells were coated with biMAb immediately following the infusion. The cytokines tumour necrosis factor-alpha, interferon-gamma and interleukin-2 showed maximum serum concentrations 2 h p.i. Tumour uptake ranged from 0.8 to 1.9% ID/kg, resulting in tumour/background ratios of 3 to 8. Our results suggest that at higher antibody dose levels OC/TR F(ab')2 causes T-cell activation with acute release of cytokines. Only low doses of biMAb can be administered safely. Despite the interaction with T cells, OC/TR F(ab')2 preferentially localizes in tumours following i.v. administration, thus offering therapeutic perspectives.

Incidence and effect on survival of abdominal wall metastases at trocar or puncture sites following laparoscopy or paracentesis in women with ovarian cancer.

The aim of this retrospective study was to examine the incidence and prognostic significance of abdominal wall metastases in patients with ovarian cancer present at the primary debulking at the entry sites of previous laparoscopy or paracentesis. The clinical records of 219 patients were studied. In 7 of 43 patients (16%) who had undergone laparoscopy and 3 of 30 patients (10%) who had undergone paracentesis previous to the primary debulking, an abdominal wall metastasis had developed at the entry sites. All metastases occurred in patients with FIGO stage IIIC-IV including ascites. Survival analysis using the Cox proportional hazards model showed that after adjustment for age, FIGO stage, histology, grade, ascites, and residual disease after primary debulking, the presence of abdominal wall metastases in the entry sites of previous laparoscopy or paracentesis was negatively, although not statistical significantly, correlated with survival (P = 0.14).

Humoral anti-OV-TL 3 response after the intravenous administration of radiolabelled Fab' or F(ab')2 fragments in ovarian cancer patients.

The human anti-mouse antibody (HAMA) response was determined in the serum of patients suspected of having ovarian cancer who underwent radioimmunoscintigraphy with either 99Tcm-OV-TL 3 Fab' (n = 20) or 111In-DTPA-OV-TL 3 F(ab')2 (n = 73). Blood samples were collected prior to and at several time points post-intravenous injection. The detection of HAMA was performed with an in-house OV-TL 3 F(ab')2-based sandwich-type immunoradiometric assay (IRMA). The homologous IRMA demonstrated that 8 of 20 (40%) patients had developed HAMA responses after injection of Fab' fragments and that 14 of 73 (19%) patients had developed HAMA responses after F(ab')2 administration. The subclass of the measured HAMA was analysed in a limited number of samples, showing IgG or IgM as well as mixed responses. The kinetics of the HAMA responses varied greatly. Our study showed the relevance of the sampling time and frequency: HAMA responses can be easily underestimated with a low sampling frequency. The homologous IRMA described in this study was able to quantify the OV-TL 3-specific HAMA responses. With additional assays, the subclass of the HAMA could be further analysed. Remarkably, the fraction of HAMA responders after injection of OV-TL 3 Fab' fragments was in the same range as the proportion of HAMA responders after F(ab')2 administration.

Analytical and clinical performance of improved Abbott IMx CA 125 assay: comparison with Abbott CA 125 RIA.

We compared the improved Abbott IMx cancer antigen (CA) 125 assay (cat. no. 7A89) with the Abbott CA 125 RIA. Serum specimens were from healthy perimenopausal women (n = 124) and from patients with benign gynecologic and nongynecologic diseases (n = 124), ovarian carcinoma (n = 104), or other malignancies (n = 193). The IMx assay detected as little as 0.193 kAU/L CA 125 (AU = arbitrary Abbott unit), demonstrated up to 29% overestimation upon serum dilution, low within-assay (2.7-5.6%) and between-assay (4.8-8.2%) CVs, and no high-dose hook effect < or = 46,000 kAU/L nor influence from human anti-mouse antibodies in serum of women injected with OC 125 F(ab')2. Values by IMx were 20% lower than by RIA for healthy perimenopausal women (n = 100; IMx = 0.80 RIA - 2.5 kAU/L), and at least 50% higher for those with benign or malignant ovarian disorders at concentrations < 100 kAU/L. Receiver-operating characteristic (ROC) curve analysis of ovarian neoplasma vs perimenopausal controls indicated a gain of specificity and sensitivity with the improved IMx assay over the RIA, but ROC performance was the same with either assay if patients with benign ovarian disorders were used as controls.

Detection of keratin subtypes in routinely processed cervical tissue: implications for tumour classification and the study of cervix cancer aetiology.

We investigated the expression of keratin subtypes 7, 8, 10, 13, 14, 17, 18 and 19 in the normal cervix, in cervical intraepithelial neoplasia (CIN) lesions and in cervical carcinomas, using a selected panel of monoclonal keratin antibodies, reactive with routinely processed, formalin fixed paraffin embedded tissue fragments. The reaction patterns derived for each keratin antibody were compared with known expression patterns of the various epithelia, previously examined in frozen tissues. Although the reactivity of the antibodies was generally acceptable, considerable modifications to the manufacturers' staining instructions were often necessary. For some antibodies, which were previously thought to be reactive with fresh frozen tissue only, we developed staining protocols rendering them reactive with routinely processed material. As with previous findings in frozen sections we observed increasing expression of keratins 7, 8, 17, 18 and 19 with increasing grade of CIN. In cervical carcinomas the differences in keratin detectability between the main categories were more pronounced than in frozen sections, probably due to fixation and processing. For routine pathology, keratin phenotyping of cervical lesions may be of value in classification. The fact that keratin 7 was detected for the first time in reserve cells, and that this keratin was also found to be expressed in a considerable number of CIN lesions and cervical carcinomas supports the suggestion that reserve cells are a common progenitor cell for these lesions.