Neoplasia Grade Research Articles

Type-specific prevalence of human papillomavirus DNA among Jamaican colposcopy patients.

Human papillomavirus (HPV) types differ in their association with cervical cancer. Therefore, the types of HPV in precancerous lesions are important. In many regions with high cancer incidence, the HPV types in precancerous lesions have not been well studied. In Jamaica, a country that has high cervical cancer incidence, 174 colposcopy patients were tested for HPV DNA using polymerase chain reaction. HPV DNA detection was strongly related to presence and grade of cervical neoplasia (P<.001). Furthermore, severe neoplastic change was most highly associated with HPV DNA types also considered high-risk for severe neoplasia in other populations. HPV-45 DNA, a high-risk type uncommon in most previously tested countries, was detected in 12% of patients who had neoplasia. Thus, cervical neoplasia in Jamaica, as elsewhere, is linked to HPV. The high prevalence of HPV-45 was notable, and its relation to high cervical cancer incidence in Jamaica must be assessed.

Das Bethesda-System - eine Verbesserung der Klassifikation der Zervixzytologie?

Cervical cytology screening programmes have significantly reduced cervical cancer mortality. In 1988 the National Cancer Institute developed a new classification for reporting cervical cytology--"The Bethesda System". The aim of our study was to compare the clinical usefulness of this new classification with the classification used in German-speaking countries (which discriminates cytologically between moderate and severe dysplasia) including a verbal classification predicting the histological grade of cervical intraepithelial neoplasia (CIN I, II, III). 671 patients with abnormal cervical cytology results and subsequent conisation or hysterectomy were included. We correlated cytological and histological diagnosis (gold standard). In cases of cytologically suggested moderate dysplasia we found histologically CIN I, CIN II and CIN III in 11%, 41% and 42%, respectively. Our results show that discrimination of CIN II and CIN III by means of cytology is limited. Using our therapy schedules we found that adequate therapy is possible by each of the cytological classification systems. The cervical smear is used as a screening test to determine which women require further examination using colposcopy. Under these circumstances an adequate therapy is possible with both classifications. The results underline the importance of colposcopy in the management of cervical dysplasia. As long as conisation is commonly used in German-speaking countries as the only diagnostic tool after an abnormal cervical smear the Bethesda System increases the risk of overtreatment.

Chemoprvention traials in the cervix: Design, feasibility, and recruitment

The cervix is an ideal organ for chemoprevention studies and the study of squamous carcinogenesis. In chemoprevention trial design, four factors are important: high-risk cohorts must be identified; suitable agents must be selected; study designs should include Phase 1, II, and III; and studies should include the use of surrogate endpoint biomarkers. High-risk cohorts can be selected for Phase I, II and III trials in the cervix, for example, patients with high grade lesions such as cervical intraepithelial neoplasia (CIN) grade 3 and carcinoma in situ (CIS). A Phase III trial might also include patients with lesions infected with oncogenic HPV types. The cervix is accessible and can be safely followed with Papanicolaou (Pap) smears and colposcopy. Suitable agents include those likely to work in squamous lesions, including retinoids, difluoromethylornithine, beta-carotene, and others. In Phase I chemopreventive studies, does are de-escalated rather than escalated, determining toxicity and optimal dose schedule. Phase II studies looking at effectiveness need placebo control groups since regression of high-risk lesions is possible. Phase III studies, now multicentric, should be carefully designed and include wide patient representation in order to evaluate the risk-benefit ratio of therapy, focusing on cancer incidence reduction. Surrogate endpoint biomarkers include quantitative histopathology, biologic measures of proliferation, regulation, differentiation, genetic instability, and fluorescence emission. Quantitative histopathologic markers include nuclear grading (i.e., shape, area, optical density, texture), nuclear pleomorphism, ploidy, and nucleolar size and position. Biomarkers under study at the present time in the cervix include proliferation markers (PCNA), regulation marker (EGFR, ras, myc, p53, retinoic acid receptors, ODC, spermidine/spermine ratios), differentiation markers (involucrin, cornifin, keratins), and markers of genetic instability (chromosome polysomy). Fluorescent spectroscopy uses light to probe the biochemical properties of tissue. This technique provides an automated diagnosis in real time with comparable sensitivity and specificity to colposcopy and can be used to monitor lesions in chemoprevention trials. Recruitment designs for cervix studies need to include a large referral population and patients with sufficiently large lesions. Clinicians involved in such studies need to stress contraception and smoking cessation, deal with language barriers, and provide compensation for child care and parking to patients in order to increase compliance.

Role of DNA Ploidy and ERB-B2 Oncogene Expression in the Prognosis of Endometrial Carcinoma

Seventy-three patients with endometrial carcinoma have been retrospectively evaluated in this paper. Stage, grade, depth of myometrial invasion, flow cytometric DNA ploidy and ERB-B2 oncogene expression by immunohistochemical method have been analyzed on paraffin embedded tissue. Results showed the existence of a significant correlation between stage and grade of neoplasia and between DNA ploidy and course of disease; it has been observed that patients with aneuploid tumor tend to have a shorter time before relapse of disease. No significant correlation between depth of myometrial invasion and survival was found. Besides, it has been shown that tumours with ERB-B2 oncogene hyperexpression seem to have a more aggressive evolution.

Global DNA hypomethylation increases progressively in cervical dysplasia and carcinoma.

Global DNA hypomethylation has been observed in some human neoplasms and has been implicated as an important factor in carcinogenesis. The current study was designed to assess whether DNA hypomethylation occurs in cervical dysplasia and cancer, and to determine the relationship between the degree of DNA hypomethylation and the grade of neoplasia. Cervical biopsy specimens were obtained from colposcopically identifiable lesions in 41 patients with abnormal Pap smear results. The extent of global DNA methylation was assessed by incubating the extracted DNA with [3H]-S-adenosylmethionine and Sss1 methyltransferase, an enzyme that specifically catalyzes the transfer of methyl groups to cytosine residues in the cytosine-guanine doublet. The degree of exogenous 3H-methyl group incorporation into the DNA therefore is related reciprocally to the extent of endogenous DNA methylation. These data were compared with the histopathologic classification of the lesions. The extent of 3H-methyl group incorporation was increased threefold and sevenfold in the DNA from cervical dysplasia and cancer, respectively, compared with the DNA from normal cervical tissue (P = 0.006, analysis of variance). Significant incremental increases in DNA hypomethylation were observed in the progression from normal and low grade squamous intraepithelial lesions (SIL) to high grade SIL and to cancer (P < 0.0001, trend). These data show that global DNA hypomethylation is a significant epigenetic event in cervical carcinogenesis and that the degree of DNA hypomethylation increases with the grade of cervical neoplasia. These data suggest that global DNA methylation may serve as a biochemical marker of cervical neoplasia.

Accuracy of cervical smears in predicting the grades of cervical intraepithelial neoplasia.

This is a retrospective study carried out to assess the correlation between the cytology and histology of cervical intraepithelial neoplasia in 1325 women. A poor correlation between the cytologic and histologic diagnosis of the various grades of CIN was shown. Forty-one percent of smears with repeated borderline change and 50% of those predicting CIN1 showed a higher grade of CIN on histology. The overall apparent false negative rate of cervical smears for high grade CIN (CIN2 and CIN3) was 19% and for CIN3 alone was only 3%. It is therefore concluded that there is a consistent tendency for cervical cytology to underestimate the severity of histologic lesions and it is therefore important that the clinicians ensure adequate follow-up of patients whose smears show a lesser degree of abnormality.

Oncogene expression in cervical intraepithelial neoplasia and invasive cancer of cervix

Abstract Expression of the oncogenes Ha-RAS, c-MYC, and ERB-2 was investigated with an automated image analysis system in 12 specimens of normal cervix, 10 of cervical intraepithelial neoplasia (CIN) grade 1,24 of CIN 3, and 10 of invasive cancer of the cervix. There was amplification of all three onocogenes in CIN 3 and invasive cancer compared with normal cervix and CIN 1. The difference was most pronounced with an antibody to the RAS p21 protein, with no overlap between CIN 3 and the normal range. This method might be useful in screening for cervical neoplasia, and for the determination of which CIN lesions require treatment.

CO2 laser resection for preneoplastic and initially invasive neoplastic lesions of the penis: Indications and technique

Superficial resection of preneoplastic and initially invasive penile lesions by CO2 laser has been developed as an alternative treatment modality to traditional surgical and destructive methods. Hyperkeratosis, pigmented lesions, chronic inflammatory disease, erythroplasia of Queyrat, Bowenoid papulosis are the main diagnostic and therapeutic indications. Therapeutic resection is indicated for histologically proven penile intraepithelial neoplasia (PIN) grade II and III, and initially invasive squamous cell carcinoma. Conservative laser resection is also indicated for exophytic, superficially infiltrating T1NO squamous cell carcinoma, responsive to systemic chemotherapy. Laser excisional procedures are always performed in association with the operating microscope, under local anaesthesia, often on an outpatient basis. Based on the disease extent, partial or total glans surface resection can be performed or associated with circumcision. Surgical specimens are always adequate for histological examination as to the extent of the disease in depth and width. Uncleared margins of resection indicate the need for further treatment. Technical, anatomical, and functional results confirm the clinical effectiveness of this microsurgical approach for selected lesions.

The Cytological Prediction of Cervical Intraepithelial Neoplasia In Colposcopically Directed Biopsies

The tissue sections and preceding cervical smears of 1262 women who had colposcopic cervical biopsies were reviewed and the reports correlated. Close correlation between the cytological and histological findings, to within one histological grade of cervical intraepithelial neoplasia (CIN), was noted in 86% of cases. However, the biopsy was negative, or contained evidence of wart virus infection only, in 24% of cases where dyskaryotic cells had been observed in the cervical smear. Of particular concern was the fact that negative histological findings were recorded in 13% of cases where the smear contained cells showing a moderate dyskaryosis and in 1.26% of cases where the smear showed severe dyskaryosis. This suggests that colposcopically directed biopsies do not always reflect the underlying pathological changes in the cervix. Management of these cases is discussed. In 45 women with a normal cervical smear prior to biopsy, histology revealed seven cases of CIN 3 and one case of invasive squamous carcinoma. This indicates that referral for colposcopy is advisable whenever there is clinical suspicion of cancer, even if the cervical smear report is normal.

Vaginal Epithelial Abnormalities in Patients with CIN

Of 4147 women who had CIN treated by laser at the Regional Gynaecological Oncology Centre, Queen Elizabeth Hospital, Gateshead, 103 (2.5%) had co-existing vaginal epithelial abnormalities. CIN 3 was the histological diagnosis most often associated with vaginal lesions. The upper vagina was almost always involved. In 67% the lesion in the cervix appeared to be confluent with that in the vagina. Even when the lesions were confluent, biopsies form the cervical and vaginal components did not always show the same grade of intraepithelial neoplasia and in some biopsies they showed different lesions. Laser treatment appears to be effective for the vaginal lesions and is therefore recommended although, in selected patients, careful follow up alone may suffice.

Stereological estimates of nuclear volume in squamous cell carcinoma of the uterine cervix and its precursors

Using modern stereology, this study was carried out to obtain base-line data concerning three-dimensional, mean nuclear size in precancerous and invasive lesions of the uterine cervix. Unbiased estimates of the volume-weighted mean nuclear volume (nuclear vv) were obtained by point-sampling of nuclear intercepts in 51 pre-treatment biopsies from patients with invasive squamous cell carcinomas (SCC). Vertical sections from 27 specimens with cervical intraepithelial neoplasia (CIN) grades I through III were also investigated, along with 10 CIN III associated with microinvasion (CIN III + M). On average, nuclear vv was larger in SCC than in CIN III and CIN III + M together (2 P = 8.9 . 10(-5). A conspicuous overlap of nuclear vv existed between all investigated lesional groups. The reproducibility of estimates of nuclear vv in biopsies with SCC was acceptable (r = 0.85 and r = 0.84 in intra- and inter-observer studies, respectively). The efficiency of the sampling scheme was high, with more than 60% and more than 80% of the total observed variance contributed by differences between individual lesions with CIN and SCC, respectively. Estimates of nuclear vv based on sampling within the whole epithelial thickness and on sampling in the lower one-third in CIN I and the lower two-thirds in CIN II lesions were of the same magnitude. Approximate estimates of the absolute variation of nuclear vv were directly proportional to individual estimates of nuclear vv, whereas the relative variation of nuclear vv tended to decrease with increasing mean nuclear volume. Based on the rather small number of cases investigated, estimates of nuclear vv are unable to distinguish between different grades of CIN. However, the estimation of nuclear vv is well-suited for the purposes of objective grading of malignancy in SCC.

Colposcopic Features of Papillomaviral Infection and Premalignancy in the Female Lower Genital Tract

Colposcopy plays an important role in the investigation and direct management of papillomavirus infection of the female lower genital tract. The colposcopic appearance of subclinical papillomavirus disorders resembles intraepithelial neoplasia, and the matter is further confused in that subclinical lesions are often accompanied by intraepithelial neoplasia into which they grade with indefinite borderlines. High accuracy in prediction of histologic diagnosis in the spectrum that ranges from subclinical papillomavirus infection to major grades of intraepithelial neoplasia may be achieved by a system of grading of colposcopic appearances.

Glutathione S-transferase (placental) as a marker of transformation in the human cervix uteri: an immunohistochemical study

Using an indirect immunohistochemical technique on paraffin sections, employing a polyclonal antibody to the acidic (placental) form of glutathione-S-transferase (GST), we have evaluated cytoplasmic and nuclear staining in a series of 67 cervical biopsies including normal non neoplastic tissue, immature squamous metaplasia, all grades of cervical intraepithelial neoplasia (CIN) and invasive carcinomas of keratinising and non-keratinising types. No differences in cytoplasmic staining between the varied lesions studied were seen. However, there were marked differences in nuclear staining. While normal non-neoplastic stratified squamous epithelium showed weak staining of the lower one-third of the epithelium only, in immature squamous metaplasia and in all grades of CIN there was intense nuclear staining in all layers of the epithelium. Invasive carcinomas showed generally less intense nuclear staining than CIN lesions. Endocervical cell nuclei also showed intense nuclear staining. These findings indicate that GST is of limited use as a marker of transformation in the human cervix uteri.

Histopathological grading of cervical intraepithelial neoplasia (CIN)—is there a need for change?

Evaluation du systeme de grading histopathologique des neoplasies cervicales intra epitheliales (CIN) et de ses difficultes pratiques d'application. Proposition d'une etude combinant une analyse precise du grading des CIN par un echantillon d'anatomo-pathologistes avec une identification des sous-types de papillomavirus en cause par hybridation in situ

A Study of Nucleolar Organizer Regions in Cervical Intraepithelial Neoplasia and Human Papillomavirus Infection

A silver colloid technique for nucleolar organizer region-associated proteins (AgNORs) was applied to sections of cervix that comprised cervical intraepithelial neoplasia (CIN) grades I to III, koilocytosis indicative of human papillomavirus infection, squamous metaplasia, and basal cell hyperplasia. The AgNOR count was compared both within and between specimens. Proliferative activity was investigated by flow cytometric analysis. Significant differences in AgNOR numbers were found between normal internal controls and the lesions investigated. A correlation was found between the proliferative index (%S + G2) determined by flow cytometry and the number of AgNORs in cases of CIN.

Grading of cervical intraepithelial neoplasia.

Grading of cervical intraepithelial neoplasia.

Grading of cervical intraepithelial neoplasia

Grading of cervical intraepithelial neoplasia

Grading of cervical intraepithelial neoplasia.

Grading of cervical intraepithelial neoplasia.

Grading of cervical intraepithelial neoplasia

Grading of cervical intraepithelial neoplasia

Grading of cervical intraepithelial neoplasia

Grading of cervical intraepithelial neoplasia