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Two common tissue sampling techniques--colposcopic biopsy and cervical scrape--and two common human papillomavirus (HPV) detection techniques--Southern blot and dot blot (SB and ViraPap [VP])--were compared to determine whether differences in these techniques alter correlations between "oncogenic" HPVs and cervical neoplasia. In 87 women with persistently abnormal Papanicolaou (Pap) smears, concurrent biopsy and scrape specimens contained HPV in 21 (24%) and contained no HPV in 26 (30%); 30 scrape specimens (34.5%) tested positive when the biopsy tested negative and 10 (11.5%) scrape specimens tested negative when the biopsy tested positive (overall concordance, 54%). Concordance for the most prevalent HPVs (16/18) was 59%. In carcinoma in situ, HPV was found in biopsy samples significantly more frequently than in scrape specimens: 17 of 23 (75%) biopsy samples versus 9 of 23 (39%) scrape specimens (P = 0.018). Conversely, in mild or no dysplasia, 0 of 42 biopsy samples tested positive for HPV 16/18 compared with 12 of 42 scrape specimens (29%; P = 0.0001). Of 229 specimens analyzed by SB and VP, 43 (19%) tested positive and 148 (65%) tested negative for HPV by both methods (concordance, 84%). Corroborative results indicated that 29 of 35 (83%) VP-positive SB-negative results were truly positive compared with none of three SB-positive VP-negative results. Both the cervical sampling technique and the method for HPV detection can significantly affect statistical correlations between cervical dysplasia and HPV type.
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PMID:Human papillomavirus infection of the uterine cervix. Tissue sampling and laboratory methods affect correlations between infection rates and dysplasia. 131 86

Human papilloma virus type 16 (HPV 16) DNA is found in about 50% of cervical squamous cell carcinomas (SCCs), and this association has raised the possibility of a causal role for HPV 16 in cervical carcinogenesis. We have tested this hypothesis by assaying a series of biopsies (n = 119) ranging from normal mucosa to infiltrating SCC with the PCR-technique for the presence of HPV 16 DNA. While HPV 16 DNA was detected in 50% of our cases with invasive SCC, the incidence of HPV 16-positive samples was about 10% in all other biopsies ranging from normal mucosa to cases of carcinoma in situ. HPV 16 therefore appears to be involved in late tumor promotion but not in early tumor development.
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PMID:Increased detection of HPV 16 virus in invasive, but not in early cervical cancers. 131 24

The Ag-NOR staining technique for nucleolar organizer regions (Ag-NORs) was applied to 37 biopsies of the uterine cervix taken from colposcopically abnormal areas. Histological examination of the sections showed that 13 patients had condylomatous lesions without atypia, 15 had CIN I, 4 had CIN II, 3 had CIN III and 2 carcinoma in situ. The mean numbers of Ag-NORs in parabasal and basal cells of squamous epithelium increased progressively from CIN I to CIN III-CIS. There was no significant difference between the Ag-NOR count in condylomatous lesions and CIN I. Significant differences were found between the number of Ag-NORs in condylomatous lesions and in the various grades of CIN. The Ag-NOR technique is useful in the diagnosis of cervical intraepithelial neoplasia and confirms the need to regard condylomata of the uterine cervix as intraepithelial neoplasia grade I and recommend these patients for follow-up.
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PMID:Nucleolar organizing regions in human papillomavirus infection and in cervical intraepithelial neoplasia. 131 4

Researchers in Spain conducted a literature search of the medical database called MEDLINE, of the Spanish Medical Index, and of all references in recovered pertinent articles to conduct a metaanalysis of epidemiologic studies that dealt with the association between oral contraceptive (OC) use and cervical cancer. They analyzed data from 51 studies (18 cross-sectional studies, 22 case-control studies, and 12 cohort analyses) in 58 publications. They considered 30 studies to be likely biased. These 30 studies were included in the large metaanalysis (metaanalysis I), but excluded from metaanalysis II. They discarded 3 studies because they were unable to derive a summary relative risk (RR) from 1 study, unable to compute the variance of the RR from another. Participants in the 3rd study already had cervical dysplasia. RR estimates of metaanalysis I were lower than those of metaanalysis II. The researchers confined their comments to metaanalysis II. Overall findings included an RR for dysplasia of 1.52, for carcinoma in situ of 1.52, and for invasive cancer of 1.21. This risk increased with duration of OC use. A significant linear dose-response effect occurred for dysplasia (p.01 for cohort studies only), carcinoma in situ (p.01 overall), and invasive cervical cancer (p.01 overall). Since the risk increased at all stages of cervical cancer, it suggested that OCs may be tumor initiators. When the researchers pooled risk estimates of all stages of cervical cancer study, they found a very significant heterogeneity which decreased with stratification by stage and design. This indicated that OCs' effect on cervical cancer risk may depend on the stage of its natural history. Since hormone dose has decreased over time, the researchers did not know whether the RR for currently marketed OCs remains. Nevertheless they recommended all women who had every sued OCs to visit a health practitioner periodically for early detection of cervical cancer.
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PMID:Oral contraceptives and cancer of the cervix uteri. A meta-analysis. 132 13

Cystatin A was immunohistochemically demonstrated in the normal squamous epithelium of the uterine cervix, particularly in the parabasal and superficial cell layers whereas it was absent or scanty in the basal cells and in areas with parakeratosis. Cystatin A was also found in neoplastic lesions (dysplasia, carcinoma in situ and squamous cell carcinoma), but less abundant than in normal squamous epithelium. The immunoreaction in intraepithelial neoplasia was closely related to the degree of morphological maturation of the squamous cells with more abundant cystatin A in low grade dysplasia and less in high grade dysplasia and carcinoma in situ. In squamous cell carcinoma, cystatin A was often abundant in highly differentiated areas and almost absent in poorly differentiated ones. Cystatin A was found in the squamous epithelium in herpes and in condylomatous lesions. It was also found in the cytoplasm of neutrophils, but not in lymphocytes and plasma cells. In unspecific cervicitis, cystatin A was found extracytoplasmatically as small vesicles in the epithelial-stromal junction. The implications of cystatin A in neoplastic, virus, and inflammatory processes are discussed.
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PMID:Immunolocalization of cystatin A in neoplastic, virus and inflammatory lesions of the uterine cervix. 132 33

Forty-nine patients with assumed extragonadal germ-cell tumors (retroperitoneum: 39, mediastinum: 8, CNS: 2) were included in the present study. The patients were treated with 'high' (40 mg cisplatin/m2 and 200 mg etoposide/m2 daily x 5) or 'conventional' (20 mg cisplatin/m2 and 100 mg etoposide/m2 daily x 5) doses of cisplatin and etoposide together with bleomycin, depending on the presence or absence of poor prognosis factors. Forty-six patients were evaluable for response and 3 patients were classified as non-responders (1 early death, 2 toxic deaths). Eighty percent obtained complete remission and 76% are alive without evidence of disease after a median observation time of 41 months (88% of patients with primary tumor in the mediastinum, 72% with tumor in the retroperitoneal area, 87% of patients with seminoma and 71% with non-seminoma, respectively). In 48 patients testicular biopsies were performed. In 42% of patients with primary retroperitoneal tumors, carcinoma in situ testis (CIS) was diagnosed. None of the patients with tumors in mediastinum or CNS had CIS in the testicles. The therapeutic outcome for patients with extragonadal germ-cell tumors is now similar to that of patients with very advanced testicular cancer when considered in relation to the presence of prognostic factors. The coexistence of CIS and retroperitoneal tumor could indicate that these tumors are not truly extragonadal or that these lesions have a common malignant progenitor.
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PMID:Management of extragonadal germ-cell tumors and the significance of bilateral testicular biopsies. 132 76

The characteristics of one of a group of monoclonal antibodies named BIU-H6 are reported. Using McAb BIU-H6, by ABC-immunohistochemical staining directed against 34 bladder cancers and 5 normal bladders. It was found that BIU-H6 does not react with normal bladder epithelial and adenocarcinoma of the bladder, but with transitional cell carcinoma, squamous cell carcinoma and CIS of the bladder. The staining characters were variant according to the different grade/stage of the cancer. The result shows that BIU-H6 antigen is a tumor associated antigen of poorly differentiated and invasive carcinoma of the bladder.
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PMID:[Characterization of monoclonal antibody (BIU-H) directed against bladder cancer and its pathologic feature]. 132 48

Vaginal and vulvar scrapes from 30 patients which have HPV types 16 or 18 positive cervical neoplasia (13 of mild dysplasia, 5 of moderate dysplasia, 4 of severe dysplasia, 3 of carcinoma in situ, and 5 of invasive carcinoma) were examined by the polymerase chain reaction (PCR), to detect amplified E7 gene of HPV types 16 and 18 DNA sequences. In 24 vaginal and 15 vulvar scrapes, the same type of HPV as in cervical scrapes was detected. The frequencies of HPV DNA in vaginal and vulvar scrapes for histological diagnosis of cervical neoplasia were 84.6% (11/13) and 53.8% (7/13) in mild dysplasias, both were 100% (5/5) in moderate dysplasias, 75% (3/4) and 25% (1/4) in severe dysplasias, 66.7% (2/3) and 33.3% (1/3) in CISs, and 60% (3/5) and 20% (1/5) in invasive carcinomas, respectively. The results of vulvar scrapes showed that the frequency of HPV DNA in mild and moderate dysplasias was significantly higher than that in severe dysplasias, CISs and invasive carcinomas (p < 0.05). We suggest that, in addition to the investigation for the natural history of HPV infection, cell dynamics, local immunological status and any other factors in the HPV-infected lesion must be investigated to clarify the carcinogenesis of HPV in the uterine cervix. Furthermore, HPVs detected in the vagina and vulva were thought to have disappeared without reaching an integrated form during the follow-up of cervical neoplasia with HPV infection over a long period.
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PMID:[Molecular biological study on multifocal infection of HPV in uterine cervix, vagina and vulva]. 133 14

A fetal testis with abnormal germ cells similar to the cells of intratubular germ cell neoplasia (ITGCN) or so-called carcinoma in situ is presented. Elective abortion was performed in week 18 of the pregnancy of a 26-yr-old woman, because of 21 trisomy (Down's syndrome) at amniocentesis. At microscopical examination abnormal germ cells were found, similar to those occurring in the adult testis and with the same distribution as those described in ITGCN in children with dysgenetic gonads and with androgen insensitivity syndrome. PAS positivity and placental-like alkaline phosphatase (PLAP) was demonstrated in the abnormal germ cells. The finding indicates that the first event of germ cell tumor oncogenesis may take place before birth, in utero or even before. The occurrence of ITGCN in Down's syndrome has not been reported previously but is likely to occur, as there is evidence that these patients have increased risk of developing germ cell tumors.
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PMID:A fetal testis with intratubular germ cell neoplasia (ITGCN). 134 19

We have investigated whether monoclonal antibody (PC10) of proliferating cell nuclear antigen (PCNA) could be useful as a marker of proliferating cells within formalin-fixed, paraffin-embedded tissue sections of 140 gynecological tumors and their related lesions. There was a positive correlation (r = 0.76) between the labelling index for PCNA and that for Ki67. Immunohistochemical staining for PC10 was confined to the nucleus and showed a diffuse or granular pattern or a mixture of both. The distribution of PC10 staining in non-neoplastic tissues was localized to proliferating cell compartments. In malignant tissues, the localization of the distribution of PCNA-positive cells came to be lost and the proportion of positive cells varied from case to case as well as from field to field within the same tissue section. The cases in which more than 31% of cells were positive for PCNA were as follows: Cervical squamous dysplasia 2/3, squamous carcinoma in situ 2/5, microinvasive squamous carcinoma 2/2, invasive squamous carcinoma 9/13, adenocarcinoma in situ 4/4, microinvasive adenocarcinoma 3/3, invasive adenocarcinoma 6/7, endometrial adenocarcinoma 6/25, ovarian epithelial malignant tumors 11/17, sex cord stromal tumors 2/14, and germ cell tumors 3/22. It is concluded that immunohistochemical staining for PC10 may be useful as a marker for proliferating activity of the cells both in normal and tumor tissues rather than for malignancy.
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PMID:[Immunohistochemical study of proliferating cell nuclear antigen (PCNA) in gynecological tumors and their related lesions]. 134 57


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