Neoplasia Grade Research Articles

Analysis of the VEGF family and their receptors in serum/plasma of patients with pre-invasive and invasive cervical cancer

5016 Background: The vascular endothelial growth factor (VEGF) family and their receptors are essential regulators of angiogenesis and lymphangiogenesis. This study examined the significance of circulating VEGF, VEGF-C, VEGF-D and their receptors VEGFR-1 and VEGFR-2 in patients with preinvasive and invasive cancer in relation to conventional prognostic parameters. Methods: Blood samples were obtained from 125 women before initial treatment (CIN I-III n = 50; FIGO stage I-IV n = 51; relapse n = 24). Plasma (p) and serum(s) levels of pVEGF, sVEGF-D, sVEGFR-1, sVEGFR-2 (R&D Systems, USA) and sVEGF-C (IBL, Japan) were determined by using a quantitative sandwich enzyme-linked immunosorbent assay (ELISA). Results: The highest level of pVEGF (p = 0.007) and sVEGFR-2 (p = 0.014) were detected in patients with recurrent disease, whereas the highest level of sVEGF-D (p = 0.046) were measured in patients with preinvasive lesions (CIN I-III). Furthermore, significantly elevated levels of sVEGF-C (p = 0.021) were detected in early stages (FIGO I-II) in comparison with advanced stages (FIGO III-IV) of cervical cancer. No significant difference in concentration was observed between the various grades of cervical intraepithelial neoplasia (CIN I-III). Correlations between conventional prognostic markers such as lymph node status (N0/N1), lymphangioinvasion (L0/L1), angioinvasion (V0/V1) and grading (G1/G2/G3) were investigated. Increased plasma levels of VEGF (p = 0.036) correlate with the dissemination of tumor cells to regional lymph nodes (N1),whereas serum VEGF-D levels were significantly decreased in women with lymph-node involvement (N1) (p = 0.045) and vascular invasion (L1) (p = 0.019). None of these members of the VEGF family were found to correlate significantly with histological subtype (squamous cell carcinoma, adenocarcinoma, adeno-squamous cell carcinoma) or grading of the tumor cells (G1/G2/G3). Conclusions: These results show that circulating concentrations of VEGF are associated with the stage of disease. In an early stage of cervical cancer a switch to a lymphangiogenic phenotype (VEGF-D, VEGF-C) might be possible. No significant financial relationships to disclose.

Human papillomavirus status in cervical scrapes and biopsy specimens using the HPV genotyping DNA microarray

There are over 100 subtypes of human papillomavirus (HPV) and HPV infections are associated with benign and malignant lesions of cutaneous and mucosal epithelia. Although several studies have compared the HPV status in cervical scrapes and biopsy specimens it still remains uncertain as to how well each of these clinical samples represents the actual HPV status of the patient’s cervix. To investigate whether the HPV status in scrape samples represents that in the overall cervix the HPV status of a total of 190 scrapes and biopsy specimens from 95 women was assessed by using a highly sensitive HPV genotyping DNA microarray. The concordance of HPV detection in both the cervical scrapes and biopsy specimens was shown to be no significant difference in grade of cervical neoplasia (p = 0.54) and the frequency of complete concordant genotyping results was also not significantly different in each class of cervical neoplasia (p = 0.229). (excerpt)

The study of dynamic chemical magnifying endoscopy in gastric neoplasia

We assessed the usefulness of acetic acid-enhanced magnifying endoscopy in the diagnosis of gastric neoplasia. Forty-five patients (27 men, 18 women; median age 61.6 years) with gastric carcinoma or adenoma were enrolled in a prospective trial of enhanced magnifying endoscopy after instillation of 1.5% acetic acid. Acetic acid-enhanced magnified views of carcinoma or adenoma and the surrounding non-neoplastic mucosa were observed, and the duration of whitening time of each lesion was recorded. Magnified views of carcinoma showed a minute, grain-like pattern that differed from the surrounding noncancerous mucosa. The histopathologic diagnostic criteria were based on the Vienna classification of GI epithelial neoplasia. The mean duration of whitening differed with each histologic type: low-grade adenoma, 94 seconds; high-grade adenoma, 24.3 seconds; noninvasive carcinoma, 20.1 seconds; invasive intramucosal carcinoma, 3.5 seconds; and submucosal carcinoma or beyond, 2.5 seconds. The duration in the non-neoplastic surrounding mucosa was 90 seconds. After the disappearance of whitening in the carcinoma, the irregular pattern of the carcinoma reappeared, and the contrast between carcinomatous microvessels and the whitened non-neoplastic tissue became very clear on magnifying endoscopy. In accordance with the duration of whitening, more than 1 minute was termed "continuous whitening," from 31 to 60 seconds was "delayed disappearance of whitening," from 30 to 6 seconds was "early disappearance of whitening," and 0 to 5 seconds was "no response." Acetic acid-enhanced magnifying endoscopy was useful for the diagnosis of gastric adenocarcinoma. The duration of whitening differed among grades of neoplasia, and it was possible to observe changes in the whitening with time. Acetic acid-enhanced magnifying endoscopy, therefore, can be termed "dynamic chemical magnifying endoscopy."

The distribution of neoplasia arising on the cervix: Results from the ALTS trial

This study was undertaken to evaluate the topographic distribution of precancerous intraepithelial lesions on the cervix. We studied the distribution of cervical biopsies and location of acetowhite lesions as determined by cervigrams among women who underwent a colposcopic examination and biopsy during the ASCUS-LSIL Triage Study (ALTS). More biopsies were taken in the 12 o'clock (41.4%) and 6 o'clock (28.4%) quadrants than in 3 o'clock and 9 o'clock quadrant (15.8% and 14.5%, respectively) (P<.001). The proportion of abnormal histology per biopsy, and the grade of neoplasia, did not vary significantly by position. Cervigrams demonstrated visible intraepithelial lesions and acetowhitening more common on the anterior and posterior quadrants of the cervix. More cervical intraepithelial neoplasia might develop at the anterior and posterior lips of the cervix. However, the evidence is weak and confounded by a tendency of the anterior and posterior quadrants to be acetowhite even in the absence of cervical intraepithelial neoplasia.

Human Papillomavirus (Hpv) Typing in Relation to ras Oncogene mRNA Expression in HPV-Associated Human Squamous Cervical Neoplasia

Human papillomavirus (HPV) has been identified as the principal etiologic agent for cervical cancer and its precursors. Different HPV types have been associated with different oncogenic potential. The purpose of this study was to evaluate the relationship between specific HPV type infection and expression pattern of the ras family oncogenes in different grades of HPV-associated human cervical neoplasia. HPV typing was performed using polymerase chain reaction (PCR) in 31 HPV-positive human cervical specimens from patients with squamous intraepithelial lesions (SIL) or squamous cervical carcinoma (SCC). The mRNA expression levels of H-, K- and N-ras oncogenes were examined using the reverse transcriptase polymerase chain reaction (RT-PCR) technique. Statistical analyses were performed using SPSS software. Among patients with SCC, H-, K- and N-ras expression levels were higher in HPV 16/18-associated cases compared to HPV 16/18-unassociated samples (p=0.003, p=0.004 and p=0.0001, respectively). The expression levels for H-, K- and N-ras were significantly higher in SCC patients with multiple HPV infection compared with SCC patients with single HPV infection (p=0.009, p=0.01 and p=0.021, respectively). Among patients with SIL, no statistically significant relationship was found between ras expression and HPV status. Our findings indicate the possible role of ras signaling interaction with "high-risk" HPV 16/18 and multiple HPV infection in cervical cancer development.

IMMUNOHISTOCHEMICAL EXPRESSION OF LAMININ-5 IN CERVICAL INTRAEPITHELIAL NEOPLASIA

Abstract Objectives Laminin-5 is an attachment protein for epithelial cells. Several studies of a variety of cancers have reported increased expression of laminin-5 in carcinoma in situ and invasive cancer. This study was designed to investigate the correlation between the grade of cervical intraepithelial neoplasia and the immunohistochemical expression of laminin-5 in the cytoplasm and in the basement membrane underlining dysplastic squamous cells. Methods We used immunohistochemical methods to stain paraffin-embedded sections of cervical cone biopsies with a monoclonal antibody specifically targeting the γ2-chain of human laminin-5 protein. The study sample included 175 slides: 7 normal cervical epithelium, 36 lesions of mild dysplasia, 50 lesions of moderate dysplasia, 81 lesions of severe dysplasia, and 1 invasive squamous cell carcinoma. Results We found a statistically significant correlation between the grade of cervical intraepithelial neoplasia and laminin-5 immunoreactivity in the cytoplasm ( P P = 0.03) by use of the Wilcoxon rank-sum test. Conclusions According to previously published reports we confirmed with a higher number of cases a correlation of laminin-5 expression in the cytoplasm and/or basement membrane and grade of dysplastic lesion in the cervical epithelium. This study warrants further investigations with special interest to follow-up to investigate whether laminin-5 is a marker to predict the risk of progression of cervical intraepithelial neoplasia lesions.

Prevalence and Genotyping of HPV in Different Grades of Cervical Intraepithelial Neoplasia and Cervical Cancer

Objective : Our purpose was to evaluate the prevalence and genotypic distribution of HPV infection by newly developed HPV DNA chip in various cervical lesions and to assess the relationship between HPV genotypes and different grades of cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods : Between December 2001 and May 2003, 394 patients who visited Busan Paik hospital due to abnormal Pap smear or colposcopic finding, were involved and classified into 5 groups according to their cytologic diagnoses: nonspecific chronic cervicitis (n=36), ASCUS/AGUS (n=36), LSIL (n=46), HSIL (n=131), cervical cancer (n=145). We examined HPV positivity and genotype of the specimens using HPV DNA chip, which detects 22 HPV genotypes including 15 high-risk HPV groups (16/18/31/33/35/39/45/51/52/56/58/59/66/68/69) and 7 low-risk HPV groups (6/11/34/40/42/43/44). Results : The overall detection rate of HPV infection was 71.1% (280/394), and the detection rate of high-risk HPV infection was 67.0% (264/394). According to the grade of the lesions, the detection rates of high-risk of HPV infection were 19.4% (7/36) in nonspecific chronic cervicitis, 16.7% (6/36) in ASCUS/AGUS, 63.0% (29/46) in LSIL, 83.2% (109/131) in HSIL, and 77.9% (113/145) in cervical cancer. The major prevailing HPV genotypes in this study were HPV types 16, 58, 18, 35, and 52 in descending order of incidence, which averaged 86.7% for all. HPV 16 was the most common type in all the HPV-positive cases as well as HSIL and cervical cancer. HPV 18 was the second most common type in cervical cancer and HPV 58 was the second most common type in HSIL. The odds ratio was estimated to evaluate the relationship of HSIL and cervical cancer versus HPV type. HPV 16 and 35 were found to be significantly related to HSIL, cervical cancer, or HSIL and cervical cancer. HPV 58 was found to be significantly related to HSIL, or HSIL and cervical cancer. Conclusion : In our study, HPV type 16, 18, 35, 52, and 58 were confirmed to be major prevailing subtypes in CIN and cervical cancer. Our results suggest that HPV 16, 35, and 58 positive patients have a tendency to develop HSIL and cervical cancer than other HPV positive patients.

E7 proteins from oncogenic human papillomavirus types transactivate p73: role in cervical intraepithelial neoplasia.

In common with other E2F1 responsive genes such as p14ARF and B-myb, the promoter of p73 is shown to be positively regulated in cell lines and primary human keratinocytes by E7 proteins from oncogenic human papillomavirus (HPV) types 16, 18, 31 and 33, but not HPV 6. Mutational analysis revealed that transactivation of the p73 promoter by HPV 16E7 requires association with pRb. Expression of p73 in normal cervical epithelium is confined to the basal and supra-basal layers. In contrast, expression in neoplastic lesions is detected throughout the epithelium and increases with grade of neoplasia, being maximal in squamous cell cancers (SCC). Deregulation of expression of the N-terminal splice variant p73Δ2 was observed in a significant proportion of cancers, but not in normal epithelium. The frequent over-expression of p73Δ2, which has recognized transdominant properties, in malignant and pre-malignant lesions suggests a role in the oncogenic process in cervical epithelium.British Journal of Cancer (2002) 86, 263–268. DOI: 10.1038/sj/bjc/6600033 www.bjcancer.com© 2002 The Cancer Research Campaign

P73 is over-expressed in vulval cancer principally as the Δ2 isoform

p73 was studied in squamous cancers and precursor lesions of the vulva. Over-expression of p73 occurred commonly in both human papillomavirus (HPV)-positive and -negative squamous cell cancers (SCC) and high-grade premalignant lesions. Whereas expression in normal vulval epithelium was detected only in the basal and supra-basal layers, expression in neoplastic epithelium increased with grade of neoplasia, being maximal at both protein and RNA levels in SCC. p73 Δ2 was the principal over-expressed isoform in the majority of cases of vulval SCC and often the sole form expressed in SCC. Over-expression of p73 was associated with expression of HPV-encoded E7 or with hypermethylation or mutation of p16INK4a in HPV-negative cases. There was a close correlation between expression of p73 and p14ARF in cancers with loss of p53 function. The frequent over-expression of p73 Δ2 in neoplastic but not normal vulval epithelium, and its co-ordinate deregulation with other E2F-1 responsive genes suggests a role in the oncogenic process. © 2001 Cancer Research Campaign http://www.bjcancer.com

Using a new HPV detection system in epidemiological research: change of views on cervical dyskaryosis?

The prevalence of human papillomavirus (HPV) rises with increasing histological severity of neoplasia, more cigarettes smoked per day and higher lifetime number of sexual partners in women with cervical dyskaryosis. Recently, the highly sensitive SPF10 primers and Inno-LiPA (line probe assay) HPV prototype research assay became available for the detection and typing of HPV. Background: using this system, we challenged the previously reported findings. Study design: the study group comprised 304 women referred because of abnormal pap smears in whom a histological diagnosis was made. Data on the lifetime number of sexual partners and smoking behaviour were obtained by questionnaire. HPV analysis was performed on cervical scrapes obtained at the enrolment visit. Results: oncogenic HPV was found in 288 (95%) women. A total of 86 (30%) out of these 288 women disclosed multiple types. HPV 16 occurred significantly less often in multiple infections than was expected on the basis of chance alone. The grade of neoplasia was significantly associated with the presence of oncogenic HPV, and this association depended on the presence of HPV type 16. No association was found between grade of neoplasia and the presence of multiple HPV types. Neither the lifetime number of sexual partners nor smoking were associated with oncogenic HPV, the five most frequent HPV types separately or the presence of multiple types. Conclusion: we conclude that the association between the detection of HPV and the epidemiological risk factors, as found with the GP5/6 PCR in the past, could not be confirmed when using SPF10 PCR primers and LiPA HPV genotyping. We suggest that the number of sexual partners and smoking may be determinants of high HPV viral load rather than determinants of the presence of HPV per se.

Human papillomavirus (HPV) study of 691 pathological specimens from Quebec by PCR-direct sequencing approach.

Human papillomaviruses (HPV) are etiological agents of cervical cancer. In order to address clinical demand for HPV detection and sequence typing, mostly in pre-cancerous cervical lesions, we applied our two-tier PCR-direct sequencing (PCR-DS) approach based on the use of both MY09/MY11 and GP5 + /GP6 + sets of primers. We tested 691 pathological specimens, all of which were biopsies, 75% of which were diagnosed histologically as cervical intraepithelial neoplasia (CIN) grades I-III. In total, 484 samples (70%) tested HPV-positive, yielding 531 HPV sequences from 47 HPV types, including two novel types. Four most frequently found HPV types accounted for 52.9% of all isolates: HPV6, 16, 11, and 31 (21.5%, 20.0%, 7.0%, and 4.5%, respectively). Some interesting results are the following: all currently known high-risk HPV (14 types) and low-risk HPV (6 types) were detected; HPV18 was not the 1st or 2nd but rather the 4th-5th most frequent high-risk HPV type; the highest detection rate for HPV (86%) among samples suspected to be HPV-infected was found in the youngest age group (0-10 years old), including 70% (44/63) "genital" HPV types; HPV types of undetermined cervical cancer risk represented 19% and of the total HPV isolates but were strongly increased in co-infections (36.5% of all isolates). To our knowledge, this is the largest sequencing-based study of HPV. The HPV types of unknown cancer risk, representing the majority of the known HPV types, 27 of the 47 types detected in this study, are not likely to play a major role in cervical cancer because their prevalence in CIN-I, II, and III declines from 16% to 8% to 2.5%. The two-tier PCR-DS method provides greater sensitivity than cycle sequencing using only one pair of primers. It could be used in a simple laboratory setting for quick and reliable typing of known and novel HPV from clinical specimens with fine sequence precision. It could also be applied to anti-cancer vaccine development.

Adeno-associated virus and development of cervical neoplasia.

Evidence from several sources has suggested that adeno-associated virus (AAV) infection might protect against cervical cancer, in part, by interfering with human papillomavirus (HPV)-induced tumorigenesis. Detection of AAV type 2 (AAV-2) DNA in cervical tissues has been reported. However, there have been few in vivo studies of women with cervical HPV infection or neoplasia, and these have reported inconsistent results. Therefore, we used polymerase chain reaction (PCR) assays targeted to the AAV-2 rep and cap genes to test tissue specimens from women in an epidemiological study of cervical neoplasia in Jamaica. We tested 105 women with low-grade cervical intraepithelial neoplasia (CIN-1), 92 women with CIN-3/carcinoma in situ or invasive cancer (CIN-3/CA), and 94 normal subjects. PCR amplification of human beta-globin DNA was found in almost all cervical specimens, indicating that these materials were adequate for PCR testing. The prevalence of HPV DNA, determined by HPV L1 consensus primer PCR was, as expected, strongly associated with presence and grade of neoplasia. Each of the AAV PCR assays detected as few as 10 copies of the virus genome. However, none of the 291 cervical specimens from Jamaican subjects tested positive for AAV DNA. Negative AAV PCR results were also obtained in tests of cervical samples from 79 university students in the United States. Exposure to AAV was assessed further by serology. Using a whole virus AAV-2 sandwich enzyme-linked immunosorbent assay, we found no relationship between AAV antibodies and presence or grade of neoplasia in either the Jamaican study subjects or women enrolled in a U.S. cervical cancer case (n = 74) -control (n = 77) study. Overall, the data provide no evidence that AAV infection plays a role in cervical tumorigenesis or that AAV commonly infects cervical epithelial cells.

Identification of squamous intraepithelial lesions: fluorescence of cervical tissue during colposcopy.

Objective. Our objective in this study was to improve the accuracy of colposcopically directed biopsy. Method. Women attending a colposcopy clinic because of an abnormal cytological cervical smear were entered into the study. A total of 154 cervical biopsy sites were investigated, using a fluorescence device developed to examine the differences in the spectral signatures of cervical tissue in different disease states. Acetowhite changes underwent biopsy, and a spectral signal was obtained. Each biopsy-optical pair was analyzed as an independent site, and the results were presented as independent comparisons of the paired data. Two groups of data are presented. Results. The optical readings indicated the presence or absence of any grade of cervical intraepithelial neoplasia with a specificity of 94.2% and 93.3%, respectively, and a sensitivity of 93.1% and 89.3%, respectively. The negative predictive values were 96.1% and 93.3%, respectively; the positive predictive values were 90% and 89.3%, respectively. Conclusion. The accuracy of the optical readings in this series was 93 to 94%. This methodology, with its excellent sensitivity, may serve a role in ensuring that all cervical intraepithelial neoplasia grades 2 and 3 lesions are identified and are subjected to biopsy during colposcopy.

Vulvar intraepethelial neoplasia (VIN) grade 3 (bowenoid papulosis) in young females

Vulvar intraepethelial neoplasia (VIN) grade 3 (bowenoid papulosis) in young females

Prevalence of Single and Multiple Infection with Human Papillomaviruses in Various Grades of Cervical Neoplasia

Prevalence of Single and Multiple Infection with Human Papillomaviruses in Various Grades of Cervical Neoplasia

Human Papillomavirus Type 16 and Risk of Preinvasive and Invasive Vulvar Cancer: Results from a Seroepidemiological Case-Control Study

Objective To examine whether human papillomavirus (HPV) type 16 is involved in the etiology of vulvar carcinomas. Methods We studied 142 histologically confirmed cases of vulvar intraepithelial neoplasia (VIN) grade 3 and invasive vulvar cancer and 126 community controls. In addition to a detailed questionnaire through which we obtained information on putative risk factors for vulvar cancer, blood samples were collected from participating subjects and tested for the presence of antibodies to HPV-16 virus-like particles. Data were analyzed by logistic regression. Results Subjects positive for HPV-16 antibodies were at a 5.3-fold increased risk of vulvar neoplasia (95% confidence interval [CI] 2.5, 11.1), and subjects with high antibody levels were at a 20-fold increased risk of disease (95% CI 5.4, 76.7). A stronger association between HPV-16 seropositivity and disease was observed for VIN grade 3 (odds ratio [OR] 13.4; 95% CI 3.9, 46.5) than for invasive disease (OR 2.9; 95% CI 0.94, 8.7), and for invasive rumors, there was a suggestion that the association was stronger for women diagnosed with squamous carcinoma of basaloid and/or warty types (OR 3.8; 95% CI 0.76,18.9) than for those diagnosed with keratinizing squamous cell carcinomas (OR 1.6; 95% CI 0.35, 7.4). Number of sexual partners and herpes simplex virus type 2 seropositivity remained as independent risk factors for vulvar neoplasia after control for confounding by HPV-16. The risk associated with HPV-16 seropositivity was higher among smokers (OR 8.5; 95% CI 3.8, 19) than among nonsmokers (OR 3.4; 95% CI 0.85, 13). Conclusion Our results confirm that HPV is associated with vulvar carcinomas. Findings also suggest the possibility that other sexually transmitted agents might be involved in the etiology of some vulvar tumors and that smoking may be an important cofactor involved in the etiology of HPV-related vulvar tumors. Evaluation of the role of HPV types other than HPV-16 in the etiology of vulvar cancer is needed, and additional efforts aimed at further elucidating the role of smoking and other cofactors in this disease process are warranted.

Prevalence of Single and Multiple Infection with Human Papillomaviruses in Various Grades of Cervical Neoplasia

Evaluation of human papillomavirus (HPV) diversity in various grades of cervical lesions is helpful for understanding the characteristics of HPV infection in the pathogenesis of cervical neoplasia. A total of 227 women with normal cervices (n = 72), low- and high-grade cervical squamous intraepithelial lesions (SILs) (n = 55 and 53, respectively) and cervical carcinomas (n = 47) were screened for human papillomavirus (HPV) types 6, 11, 16 and 18 infection by the polymerase chain reaction. The prevalence of multiple HPV infections in patients with normal cervices, low-grade SILs, high-grade SILs and cervical carcinomas was 22.2%, 61.8%, 41.5% and 21.3%, respectively, while the prevalence of a single-type infection was 36.1%, 21.8%, 30.2% and 61.7%, respectively. HPV 16/11 and 16/18 were the most common combinations observed in multiple infections. Multiple HPV infections were seen most frequently in patients with low-grade SILs, and the prevalence decreased with increasing severity of cervical neoplasia. In contrast, infection with a single HPV type was most commonly observed in patients with cervical carcinoma, and the prevalence decreased with decreasing severity of cervical neoplasia. HPV 16 was the predominant single-type infection in patients with cervical carcinoma and this prevalence decreased steadily with decreasing severity of cervical neoplasia. Conversely, HPV 11 was the predominant single-type infection in patients with normal cervices. This prevalence decreased with increasing severity of cervical neoplasia. Patients with low-grade SILs had a higher prevalence of HPVs, regardless of single or multiple infection status, and larger copy numbers of virus genome were seen more frequently in patients with more severe lesions.

Preliminary results on the activity of cidofovir for the treatment of cervical intraepithelial neoplasia (CIN) grade III

Preliminary results on the activity of cidofovir for the treatment of cervical intraepithelial neoplasia (CIN) grade III

Prostate cancer; the interface between pathology and basic scientific research

Current research into prostate cancer increasingly demands greater input from pathologists. There is a requirement for improved morphological assessment, classification and grading of neoplasia. The provision of optimally preserved material and establishment of tissue ‘banks’ is vital to facilitate molecular biological analysis. Microdissection of archival material can provide a source of relatively pure DNA and mRNA which can be further amplified by PCR/RT-PCR. This enables allelic imbalance, point mutations and other genetic abnormalities to be demonstrated. In-situ hybridization for mRNA is feasible on fixed tissues and allows precise localization of gene expression on complex tissues or for labile gene products. Experimental models including transgenic mice and in-vitro co-culture systems require sophisticated morphological analysis. Experts in morphological analysis are essential members of basic scientific and translational research teams.

A study to determine the underlying reason for abnormal glandular cytology and the formulation of a management protocol.

A retrospective review is presented of 89 patients with glandular dyskaryosis in order to formulate a management protocol. Fifteen patients had cervical intraepithelial neoplasia (CIN) without glandular abnormality (17%). One patient had adenocarcinoma in situ of the cervix and one patient had vaginal intraepithelial neoplasia (VAIN) grade III. Twenty-two patients had endometrial carcinoma (24.5%) and 11 patients had cervical carcinoma (12.5%). Of the patients presenting with post-menopausal bleeding as well as having glandular dyskaryosis, 69% had a gynaecological malignancy. In conclusion, colposcopy and out-patient endometrial sampling are recommended in all cases. Patients with abnormal endometrial sampling require hysteroscopy. Cone biopsy is necessary to exclude occult glandular disease if cytology remains abnormal despite negative colposcopy and sampling.