Biomedical subjects

T Löning

Publications and source records attributed to T Löning.

At least 73 records · Page 4Linked to original sources

PubMed1998

Dysregulated expression of CD66a (BGP, C-CAM), an adhesion molecule of the CEA family, in endometrial cancer.

CD66a (BGP, C-CAM) is an adhesion molecule of the carcinoembryonic antigen family that has been shown to be down-regulated in colorectal, prostate, and breast cancers. The purpose of the present study was to determine its expression pattern in the normal human endometrium and in endometrial neoplasia. For this purpose, we performed immunohistochemistry using the 4D1/C2 monoclonal antibody on a series of 24 normal endometrial samples and 47 endometrial carcinomas. Strong CD66a expression was observed in glandular and luminal epithelial cells of the normal endometrium with a consistent localization at the apical poles of these cells throughout the cycle. In late secretory (premenstrual) phase, loss of cellular polarity resulted in a membranous expression pattern in some glandular cells. In the analyzed tumor samples increasing areas with a complete loss of expression were observed with increasing malignancy grade. The apical expression pattern of the normal epithelium was changed to a membranous all-around pattern in 55% of the tumors, mostly in solid areas. This change correlated with malignancy grade and could be observed in 3 of 15 G1 tumors, 4 of 12 G2 tumors, 11 of 12 G3 tumors, and 8 of 8 serous-papillary carcinomas. Areas with membranous expression pattern could be observed along with areas with a normal apical expression pattern in lower grade carcinomas and with areas with complete loss of expression in high grade tumors. Northern blot analysis showed a loss of mRNA expression in tumor samples and HEC-1B endometrial adenocarcinoma cells. Loss of protein expression in the tumor samples was also observed by Western blot. In conclusion, CD66a protein expression is dysregulated in endometrial carcinomas, showing reduction or loss of expression with increasing malignancy grade and a change from the apical to a membranous localization.

Antigens, CD↗

PubMed1997

Identification of allelic losses in benign, borderline, and invasive epithelial ovarian tumors and correlation with clinical outcome.

BACKGROUND: The somatogenetic alterations that lead to the development of benign adenomas, borderline tumors, and invasive ovarian carcinomas are not well understood. This study investigated allelic losses in these three types of ovarian tumors. METHODS: Twelve genetic regions on chromosomes 2q, 5q, 6p, 6q, 9p, 11q, 17p, 17q, 18q, and 22q were analyzed by polymerase chain reaction for loss of heterozygosity (LOH). The study was performed on formalin fixed, paraffin embedded tissue samples from 72 invasive ovarian carcinomas, 35 ovarian tumors of borderline malignancy, and 25 benign ovarian adenomas. RESULTS: LOH was found in only 8% of the analyzed adenomas (at 2q21 and 17p13) and 11% of the borderline tumors (at 2q21, 5q21, 6p21, 17p13, and 17q21). Allelic losses were noted for 77.7% of all of the invasive carcinomas analyzed. The frequency of LOH was 56% at a locus near 17p13 (TP53) and 40.5% at 17q21 (BRCA1). LOH was observed in 30.4% of informative cases at 5q21 and in 21.4% at chromosome 18q21. The chromosomal regions 2q21-22 and 9p21 had deletions at frequencies of 32.4% and 25%, respectively. International Federation of Gynecology and Obstetrics stage and the presence of LOH correlated significantly with survival but were not independent predictors of survival. Serous subtypes of invasive carcinoma were significantly more prone to deletions than nonserous tumors. CONCLUSIONS: The results of this study suggest that LOH occurs only occasionally in adenomas and borderline tumors, whereas it is frequently observed in invasive ovarian carcinomas. Therefore, other genetic events seem to be involved in early ovarian tumor development. However, the presence of multiple allelic losses is an indicator of higher stages of invasive carcinoma.

Adenoma↗

PubMed1997

p53 is a persistent and predictive marker in advanced ovarian carcinomas: multivariate analysis including comparison with Ki67 immunoreactivity.

p53 mutation and p53 protein overexpression are common findings in ovarian carcinomas. In order to evaluate the prognostic significance of the p53 status and its role in metastasis, we examined 104 ovarian carcinomas, among them 83 cases with follow-up data, and 40 pairs of primary tumors and metastases, by p53 immunohistochemistry and temperature-gradient gel electrophoresis. Comparison of primary tumors and their metastases revealed identical results in 88%-90% of the cases, indicating that, in most cases, mutant p53 occurs prior to metastatic spread and remains clonally conserved. With respect to all tumors, moderate/high p53 expression was significantly more prevalent in serous-papillary types, carcinomas with high grade, and high Ki67 scores, but was not associated with age, stage, or hormone receptor status. Kaplan-Meier analysis of 83 cases, followed-up for 9-96 months, demonstrated that moderate/high p53 overexpression in the group of 66 stage T3/M1 tumors was associated significantly (P = 0.0028 and P = 0.0105) with shorter overall and recurrence-free survival. Multivariate analysis revealed that advanced clinical stage and p53 positivity were the only independent predictive variables. No significance was seen in regard to second-look results and outcome of 50 patients receiving platinum-based chemotherapy. These observations show that p52 immunohistochemistry is an independent prognostic indicator at the given cut-off level, but does not reliably predict chemotherapy response.

Adult↗

PubMed1997

[Detection of human papillomavirus (HVP)-DNA in oral manifestation of lichen planus].

Human papilloma viruses (HPV) can be detected in different epithelia with the help of the polymerase chain reaction (PCR). The role of HPV in the development of anogenital cancers has been intensively studied, and current evidence shows that most cervical cancers are associated with so-called high risk HPV types (e.g. HPV 16 and 18). HPV-infections can also be demonstrated in oral premalignant lesions and squamous cell carcinomas. Depending on the sensitivity of the detection method, 40-67% of leukoplakias, 2.5-76% of squamous cell carcinomas and 0-87% of cases of lichen planus were described to be infected with HPV 16 or 18. Whether lichen planus can be considered as a premalignant lesion is still controversial. By the use of PCR and hybridization we found infections with the high risk HPV types 16, 18 and 31 in 42% (3/7) of the patients with lichen planus. Further investigations with a higher numbers of cases in combination with the analysis of the viral gene expression as well as the clinical and histological control of the corresponding regions are necessary. The aim of these studies is to find out the prognostic value of the HPV infection for this facultative premalignant disease.

DNA Probes, HPV↗

PubMed1997

Molecular and immunohistochemical analysis of p53 mutations in scrapings and tissue from preinvasive and invasive breast cancer.

Mutations of the p53 gene appear to be one of the most common abnormalities in human cancer. Although many studies have been published about p53 alterations in breast cancer, data on molecular biological detection of p53 mutations in in situ lesions are still rare, and the implications for breast cancerogenesis are unclear. Tissue samples from 83 patients with different stages of breast cancer and from 13 patients with benign breast lesions were screened for p53 gene mutations by polymerase chain reaction (PCR) followed by temperature-gradient gel electrophoresis (TGGE). p53 protein accumulation was analysed by immunohistochemistry (IHC). Samples were gained from fresh-frozen tissue, scrapings, or paraffin embedded tissue. Additionally, 23 pairs of primary tumours and corresponding lymph nodes were examined. p53 gene aberrations were found in 55.7% of the infiltrating carcinomas, in 31.5% of the ductal carcinomas in situ (DCIS) and in one atypical ductal hyperplasia. A positive correlation was seen with high-grade tumours and with comedo. There was no statistically significant relationship with respect to age, menopausal status, tumour size, hormone receptor status or lymphatic invasion. Concordance between TGGE and IHC was seen in only 63% of the cases analysed. However, with regard to p53 mutation screening by TGGE, a high significance (P = 0.0008) was seen between standard tissue extraction and our scrape preparation technique. Among 8 pairs of primary tumours and their corresponding lymph node metastases, only 3 harbored identical p53 mutations in the same exon, while in 5 cases with mutant p53 in the primaries, no mutation was seen in the lymph node. Our data indicate that p53 mutations are frequent in breast tumours associated with unfavorable prognosis, including high-grade or the comedo histotype. There is evidence that p53 gene alterations occur early in breast cancerogenesis, as mutations were detected not only in in situ carcinomas but also in atypical ductal hyperplasia.

Adult↗

PubMed1997

p53 gene mutations and HPV infection in primary head and neck squamous cell carcinomas do not correlate with overall survival: a long-term follow-up study.

We analyzed specimens of head and neck squamous cell carcinomas (HNSCC) from 110 patients for p53 gene mutations, and 92 of them for human papillomavirus (HPV) infection, in order to evaluate the prognostic significance of these factors by comparison with clinical follow-up data. Mutations within the exons 5 to 8 of the p53 gene were found in 48 tumors (44%). Sequencing revealed in most cases mis-sense mutations (16/21). Frequency of p53 gene mutations was not related to the tumor stage or the presence of lymph node metastases. Of the 46 tumors that were analyzed by immunohistochemistry, 26 stained positively (56%). The number of positively stained nuclei increased slightly with decreasing differentiation of the tumors, whereas no correlation was found between tumor stage and immunoreactivity. An infection with the high-risk HPV types 16 and 18 could be detected in 39/92 tumor specimens (42%). Follow-up data were obtained from 99 patients within a range of 2 to 112 months. No dependence of overall survival on the presence of p53 gene mutations or HPV infection could be observed. The absence of statistically significant correlations between p53 gene mutation and progressive disease, however, does not deny its putative relevance in early phases of tumor development.

Adult↗

PubMed1997

Differential expression of CD66a (BGP), a cell adhesion molecule of the carcinoembryonic antigen family, in benign, premalignant, and malignant lesions of the human mammary gland.

CD66a, also known as biliary glycoprotein (BGP), is a member of the carcinoembryonic antigen (CEA) family and the human homologue of the rat cell-CAM. There is evidence that aberrant expression or loss of CD66a in tumor tissue is of biological significance. No data about its expression in breast carcinoma cells and only sparse information about the expression of CD66a in normal breast are available thus far. In this study we used monoclonal antibodies to analyze the expression of CD66a and CEA in normal tissue, benign lesions, and in noninvasive and invasive carcinomas of the mammary gland. In normal tissue and benign lesions, CD66a was consistently expressed at the apical sites of epithelial cells and in myoepithelia, whereas CEA was absent or was restricted only to some apical membranes within the ductal tree. The specific staining of myoepithelia was most evident in pseudoinfiltrative radial scars and sclerosing adenosis. However, the apical expression of CD66a disappeared with the development of the malignant phenotype in noninvasive and invasive carcinomas, and changed gradually from low- to high-grade noninvasive carcinomas into a predominant uniform membrane staining all around the atypical cells. CEA expression was irregular in intensity and distribution. The native apical CD66a staining was partially preserved in some highly differentiated invasive carcinomas with a better prognosis, such as tubular and papillary carcinomas. These findings indicate that loss of CD66a expression rather than a change in staining patterns coincides with the development of the malignant phenotype.

Antibodies, Monoclonal↗

PubMed1997

Mutation of the tumor suppressor gene p53 in human prostate and bladder cancers--investigation by temperature gradient gel electrophoresis (TGGE).

PURPOSE: To test the value of a recently developed screening method for the detection of p53 mutations in prostate and bladder cancers. MATERIALS AND METHODS: Tumor tissue from 24 prostate cancers and 27 bladder cancers were evaluated. DNA of the critical p53 exons 5-8 were amplified and run on horizontal polyacrylamide gels under defined temperature conditions (TGGE) to yield specific gel shifts and sets of homo- and heteroduplexes in case of mutation. Sequencing with a laser-fluorescent electrophoresis unit was done directly from polymerase chain reaction (PCR) products and/or from reamplified mutant and wild type bands excised from the gels. RESULTS: The p53 genotype predicted from the TGGE analysis was always confirmed on the excised DNA fragments, in contrast to only 50% of cases tested by direct sequencing from mixed wild type and mutant DNA present in PCR products. With this screening protocol, 6 of 24 prostate cancers (25.0%) and 11 of 27 bladder cancers (40.7%) showed p53 mutations. At stage T1, none of prostate cancers and 41.2% of bladder cancers contained mutant p53. At higher stages (> or = T2), 30.0% of prostate cancer and 50.0% of bladder cancers were mutated. Histological tumor grading was > G1 in all but two prostate/bladder cancers with mutant p53. It appears that p53 mutations can occur early in bladder carcinogenesis. CONCLUSION: TGGE fulfills the clinical need of a rapid and specific screening method, and, at the molecular level, has the advantage of sorting out the wild type and mutant alleles for consecutive sequencing.

Adolescent↗

PubMed1997

[Gene products of human endogenous retrovirus (HERV)-K in germ cell and trophoblastic tumors].

Antibodies against Gag and Env proteins encoded by human endogenous retrovirus (HERV)-K genomes are found in the sera of patients with classical seminoma. This prompted us to study ovarian and testicular germ cell tumors, their precursor lesions, dysgenetic gonads, and trophoblast lesions for expression of HERV-K sequences by in situ hybridization using radioactive and non-radioactive probes. Expression of HERV-K sequences was found in all testicular and ovarian germ cell tumors with the exception of teratomas and spermatocytic seminomas. HERV-K expression was also found in testicular intraepithelial neoplasia (so-called carcinoma in situ) as well as in gonocytes of dysgenetic gonads. Among gestational trophoblastic lesions, HERV-K expression was regularly found in choriocarcinomas, but not in non-invasive molar lesions. There was no evidence for HERV-K expression in differentiated embryonal and adult tissues. The findings point to a common molecular pathogenesis of most germ cell tumor entities and malignant gestational trophoblastic disease. They furthermore support the concept of carcinoma in situ as a precursor lesion common to most testicular germ cell tumors. Conceivably, the detection of HERV-K gene products in body fluids and tissues will aid diagnosis and monitoring of germ cell tumors and related lesions.

Adult↗

PubMed1996

Comparison of benign and malignant endometrial lesions for their p53 state, using immunohistochemistry and temperature-gradient gel electrophoresis.

The aim of this study was to evaluate the presence and distribution of p53 alterations in pure endometrioid adenocarcinomas (n = 120) of different grades and stages, as opposed to normal endometrium (n = 13) and various risk groups of hyperplasia (n = 39). All samples were initially analysed by immunohistochemistry with the monoclonal antibody Ab-6. Normal endometria were negative. With increasing degrees of malignancy, the number of cases with p53 accumulation rose and ranged from 9% to 18% in hyperplasia, through 25% in low-grade carcinomas (G1), to 69% in high-grade carcinomas (G3). This increase was also seen when comparing tumours by stage. Of carcinomas in stage IA, only 17% showed p53 immunostaining, in contrast with 72% in stage IC. Of this material, 34 carcinomas and 8 hyperplasias were analysed for p53 mutations in exons 5-8 by means of polymerase chain reaction and temperature-gradient gel electrophoresis (TGGE). In none of 5 hyperplasia and 6 of 12 carcinomas showing p53 accumulation by immunohistochemistry, p53 mutations were detected by TGGE. In contrast, 4 of 22 carcinomas harboured mutant p53 but were negative by immunohistochemistry. Immunohistochemical and molecular investigations revealed that p53 alterations are related to the standard prognostic markers of endometrial cancer, i.e. grading and staging. TGGE, an indirect screening procedure for p53 mutations, is used to detect the type of p53 alteration and may provide additional insight into the complex figure of p53 abnormalities in the development and progression of malignant endometrial lesions.

Adult↗

PubMed1996

[Lobular cancer transformation of the female breast. Mammography diagnosis and clinical relevance].

Lobular cancerisation was diagnosed in 101 women between 1976 and 1980. Calcification in the mammograms and follow-up without mastectomy were analysed. Therapy was simple biopsy, because the term lobular cancerisation was not established at that time. Surgery was done at the University Clinic for Women and the Elim Hospital at Hamburg. Retrospective analysis of the specimens was performed at the Department of Gynaecological Histopathology of the Hamburg University Clinic. Mammograms were available in 72 cases, showing calcifications in 40 cases. It was impossible to match the calcifications in the mammograms and the histological slides. Hence, a further 23 cases from 1980 to 1990 were analysed, suffering from lobular cancerisation and ductal carcinoma in situ (DCIS). Comparing 13 mammograms showing calcifications, with large-area scans, only two showed corresponding calcifications. Based on these data a specific diagnosis of lobular cancerisation by mammography is impossible. The follow-up of 88 patients with breast-preserving surgery and lobular cancerisation showed ipsilateral invasive carcinoma in three cases (0.35% in a total of 100 follow-up years), ipsilateral DCIS in five, and contralateral invasive breast cancer in one case. The therapy of lobular cancerisation should depend on the coexisting DCIS. There is no additional risk of local recurrence by lobular cancerisation.

Breast↗

PubMed1996

CD66a (BGP), an adhesion molecule of the carcinoembryonic antigen family, is expressed in epithelium, endothelium, and myeloid cells in a wide range of normal human tissues.

CD66a, also called biliary glycoprotein (BGP), is a member of the carcinoembryonic antigen (CEA) family and of the immunoglobulin superfamily. CD66a is the human homologue of Cell-CAM, a well-defined cell adhesion molecule of the rat. In the present study a monoclonal antibody specific for CD66a was used to locate CD66a in human tissues. CD66a is expressed in epithelia, in certain endothelia, and in cells of the myeloid lineage. Hepatocytes were stained along the bile canaliculi. A characteristic apical membranous staining was observed in enterocytes, superficial absorptive cells of the colon, in the epithelia of esophageal and Brunner's glands, bile ducts and gallbladder, pancreatic ducts, proximal tubules of the kidney, prostate, endometrium, and mammary ducts. Selective staining of endothelia was present in glomeruli and vasa recta of the kidney, small placental vessels, adrenal sinusoids, endometrium, the prostate. Among the cells of the myeloid lineage, granulocytes and myelocytes were positive. The expression of CD66a by human cells and tissues is well comparable with the expression reported for Cell-CAM, the rat counterpart of CD66a. The wide tissue distribution of CD66a indicates that CD66a is a prominent human adhesion molecule.

Antigens, CD↗

PubMed1996

Differential expression of the monocyte chemoattractant protein-1 gene in human papillomavirus-16-infected squamous intraepithelial lesions and squamous cell carcinomas of the cervix uteri.

Monocyte chemoattractant protein (MCP)-1 is an important factor involved in the cross-talk between mononuclear cells and human papilloma-virus (HPV)-infected cervical epithelia. To prove the experimental model of a negative regulatory loop between the expression of the HPV oncogenes E6/E7 and the MCP-1 gene in vivo, we examined HPV-16-infected conization/hysterectomy specimens consisting of 6 low- and 6 high-grade squamous intraepithelial lesions (SILs) and 5 squamous cell carcinomas (SCCs) as well as the adjacent mucosa by isotopic RNA in situ hybridization. Langerhans cells and stromal macrophages were identified by the antibodies S-100 and PG-M1. E6/E7 expression was restricted to dysplastic or neoplastic keratinocytes, whereas MCP-1 transcripts were detectable in normal, dysplastic, and neoplastic epithelia, in endothelia, and in stromal macrophages. Langerhans cells were always negative. MCP-1 expression was predominant at the epithelial-mesenchymal junctions and especially intense when the stromal macrophage reaction was increased. Generally, the synchronous expression of E6/E7 and MCP-1 was very rare in SILs (2 of 12 cases). In high-grade SIL, MCP-1 expression was observed in 1 of 6 cases, whereas all lesions strongly hybridized with E6/E7 probes. In contrast, 4 of 5 SCCs re-expressed MCP-1, and 2 cases revealed marked transcriptional activities for both E6/E7 and MCP-1. Although preliminary, our observations lend support to the suggestion that the experimental model of transcriptional regulation and exclusion of either HPV E6/E7 or MCP-1 expression is especially pertinent to high-grade SIL, whereas in most SCCs, other environmental factors may influence this relationship.

Base Sequence↗

PubMed1995

Presence and persistence of HPV infection and p53 mutation in cancer of the cervix uteri and the vulva.

We studied 51 cervical carcinomas, among them 25 squamous-cell carcinomas (SCC) and 26 cervical adenocarcinomas (AdCa), and 40 vulvar SCC for the presence of HPV and mutant p53. HPV was detected by PCR, and p53 alterations by temperature-gradient gel electrophoresis/direct sequencing and immunohistochemistry. HPV, mostly type 16/18, was found in 80.4% of the cervical tumors (92.0% of the SCC and 69.2% of the AdCa), but in only 27.5% of vulvar carcinomas. In contrast, p53 mutations were found in 7.8% and 52.5% of cervical and vulvar tumors respectively. Mutant p53 occurred in pre-invasive vulvar lesions, indicating that this oncogenic factor is involved early in carcinogenesis. Further analysis of recurrent/metastatic lesions of 9 cervical and 14 vulvar tumors also showed remarkable differences: in cervical cancer, HPV was persistent, and p53 mutations absent, whereas in vulvar tumors, HPV was mostly absent or not persistent, and the p53 mutation rate was very high (78.6%). These observations suggest that HPV persistence is an important event for the evolution and maintenance of cervical cancer, whereas for vulvar cancers p53 mutation and not HPV activity is a central oncogenic event.

Adenocarcinoma↗

PubMed1995

p53 mutations in ovarian tumors, detected by temperature-gradient gel electrophoresis, direct sequencing and immunohistochemistry.

Samples from 94 ovarian tumors, comprising 24 cystadenomas/adenofibromas, among them 6 benign and 18 borderline tumors, one benign Brenner tumor, 39 carcinomas, 17 sex-cord stromal tumors, 5 germ-cell tumors and 8 metastatic or recurrent neoplasms were screened for p53 aberrations by polymerase chain reaction (PCR), temperature-gradient gel electrophoresis (TGGE), direct sequencing and immunohistochemistry. All sex-cord stromal and germ-cell tumors showed wild-type p53, except for a heterozygous silent germ-line mutation in one androblastoma. Somatic p53 mutations were detected in only one tumor of the cystadenoma/adenofibroma series (4.2%), in contrast to 38.5% of the carcinomas, among them 57.1% of serous papillary carcinomas, and 12.5 to 22.2% of endometrioid and mucinous carcinomas. By direct sequencing, the mutations of 13 cases were qualified as mis-sense mutations (n = 10), or 1 to 2-bp deletions (n = 3). Only 2 cases were immunohistochemically positive in the absence of detectable p53-gene abnormalities. The presence of p53 aberrations was significantly correlated with high grade, but not with stage of disease. For 21 bilateral tumors and/or tumors spread to the peritoneum, samples from both ovaries and/or ascites were analyzed. Among these, 16 cases were identical as to the p53 genotype, 5 cases showed discordant p53 states in ovary and/or in ascites DNA. We conclude that somatic p53 mutations are very frequent in serous papillary carcinomas, particularly in tumors of high grade, bilaterality, and peritoneal spread, less frequent in other carcinoma types and extremely rare in borderline and benign tumors of the ovary.

Adenocarcinoma↗

PubMed1995

HPV DNA and p53 alterations in oropharyngeal carcinomas.

We have examined a series of 37 oropharyngeal squamous cell carcinomas for the presence of HPV 6/11, 16, and 18 DNA by polymerase chain reaction (PCR)/Southern blotting and for p53 alterations by immunohistochemistry and mutation screening with temperature gradient gel electrophoresis (TGGE). HPV sequences were found in a total of 26 of 37 cancers (70.3%), most frequently HPV 16 (20/37) followed by HPV 18 (11/37). Double infections with HPV 16 and 18 were present in 5 tumours. p53 accumulation was detectable immunohistochemically in 21 of 37 carcinomas (56.8%). There were remarkable differences in the distribution of immunoreactive tumour cells in relation to the tumour grade. A mutation screening for p53 by TGGE, directed to the amplified exons 5-8, revealed p53 mutations in 14 of 37 carcinomas (37.8%). Mutations in two different exons were present in 3 tumours, 11 tumours being hit once. Exon 7 was mutated in 6 carcinomas, exons 5 and 8 in 4 cases, and exon 6 in 3 cases. When grouping the tumours with p53 mutation according to their HPV state, HPV-positive cases showed slightly more mutations (11/26) than HPV-negative cases (3/11). Only 5 of 37 carcinomas (13.5%) contained neither HPV DNA nor p53 alterations. Our results indicate that high-risk HPV and p53 mutations frequently coexist in oropharyngeal carcinomas, in contrast to genital tumours, notably carcinomas of the cervix uteri. This may reflect different pathways in carcinogenesis in squamous cell epithelium from different sites.

Adult↗

PubMed1995

[Primary lymphoma of the cervix uteri--2 case reports].

Two cases of primary non-Hodgkin's lymphoma of the uterine cervix are described. Diagnostic pitfalls and therapeutic applications of this rare disease are discussed. The main approach in local therapy is external beam radiation--with or without surgical staging. Prognosis is favourable--depending on the stage of disease.

Adult↗

PubMed1994

Polymerase chain reaction-assisted papillomavirus detection in cervicovaginal smears: stratification by clinical risk and cytology reports.

Seven hundred and twelve patients from cancer screening, pregnancy care, outpatient clinics for patients at risk for cervical dysplasia and human immunodeficiency virus (HIV) infection were tested simultaneously for cytological aberrations and human papillomavirus (HPV). Classification of these cases, and of all cytology records throughout 1991 and 1992 was performed according to the "Münchner Nomenklatur" and the Bethesda classification. HPV-directed polymerase chain reaction analysis was carried out with general primers, patients at risk for cervical dysplasia were tested by subsequent hybridization with HPV 16 and 18 probes. Patients from cancer screening and pregnancy care showed similar HPV prevalences ranging between 19.4%-24.6%. In contrast, patients from dysplasia and HIV units were infected in 56.2%-62.3% and 75.0%-76.9% respectively in centre of disease control stage III-IV, HPV detection rates in patients from dysplasia and HIV units increased gradually from 40.1%-52.9% in non-suspicious smears to 80.8%-100% in atypical smears. High risk HPV 16 and 18 infections were detected in 64% of smears with cytological evidence of HPV infection (koilocytosis) to 84.2% in severe dysplasia. Following the Bethesda guidelines, 2.9%-14.7% of all smears initially reported as Pap 2 K (suggestive of HPV infection) would be qualified as risk lesions (low grade squamous intraepithelial lesions), although they tested HPV negative in more than a third of cases. Thus, when using the Bethesda system, HPV analysis is needed to prevent overclassification and overtreatment. The "Münchner Nomenklatur" avoids this dilemma by not mixing morphological statements on infection, atypia and cancer risk.

Adult↗