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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer patients who were pregnant at the time of cancer diagnosis were identified by the National Cancer Registry of the German Democratic Republic for the years 1970 through 1979. A total of 355 such cases occurred in women aged 15-44, and during the same period 2, 103, 112 live births were registered. Rank by site in order of decreasing frequency was cervix, breast, ovary, lymphoma, melanoma, brain and leukemia. On the basis of general female population rates, 555.8 cases were expected, giving a significantly reduced observed to expected ratio (O/E) of 0.64. O/E ratios rose with age. The O/E for invasive carcinoma of the cervix was significantly elevated at 1.15; carcinoma in situ of the cervix occurred significantly less frequently than expected (O/E = 0.57). For breast, brain, melanoma and leukemia, significantly fewer cases were observed than expected. Explanations considered for the low number of pregnancy-associated incident cancer cases include underreporting of pregnancy-associated cancer, altered tumor progression in pregnancy or decreased fertility in women with early neoplastic disease.
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PMID:Pregnancy in association with a newly diagnosed cancer: a population-based epidemiologic assessment. 646 98

We have used a broad range of primers for HPV detection, using the polymerase chain reaction (PCR) so as to compare PCR typing of HPV with the results of cytological diagnosis in a New Brunswick population referred to the out-patient clinic of the Saint John Regional Hospital. The primers selected were found to be capable of amplification with high efficiency, therefore we did not perform further hybridization analysis for specific identification of HPV types. Amplification of selected fragments for detection of HPV 6, 11, 16, 18, 31 and 33 was obtained from cervical swabs collected from 154 patients. Microscopic examination was performed in duplicate samples and the results compared with the DNA-typing analysis. HPV of any of the above types was detected in 43 out of 154 patients. Among these, 32 patients showed single or multiple infections with "high-risk" HPV strains 16, 18, 31 or 33. Cytologically normal or atypical samples with any of the HPV types tested amounted to 17%, but increased to 56% in patients with CIN I, and to 100% in patients with CIN II or III. Prevalence of "high-risk" types alone increased from 15% and 10%, for normal and atypical cases respectively, to 48% for CIN I, 75% for CIN II and 100% for CIN III. Our results indicate that HPV detection and typing by this simple procedure can be a valuable indicator of cancer progression and thus can help to identify individuals at high risk in pre-malignant stages of the disease.
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PMID:PCR detection and typing of genital papillomavirus in a New Brunswick population. 840 88

Neoplasia is a progression of molecular, cellular, and tissue changes starting with a critical cell mutation and advancing by clonal evolution, involving further multiple mutations and expanding mutated clones. This process is characterized by five general stages: latency, focal growth of normal-appearing but disorganized cells, abnormal-appearing cells (dysplasia), microinvasion, and finally, metastasis. The two driving forces of neoplastic progression in an epithelium are mutagenesis and mitogenesis. These forces frequently occur concurrently, produced by exposure of the epithelium to environmental and endogenous mutagens and mitogens. The major strategy of chemoprevention is to block the effects of both mutagens and mitogens during the early stages of predysplasia and dysplasia. Surrogate endpoint biomarkers (SEBs) are tissue, cellular, and molecular changes that correlate with the later development of cancer. Because of the savings in cost, labor, and time, SEBs are urgently needed to replace the use of cancer incidence reduction as the endpoint for chemopreventive agent clinical trials. The advent of computer-assisted cytometry allows each of the seven basic criteria of dysplasia to be individually assayed as an SEB. Since the dysplastic changes that characterize intraepithelial neoplasia are embodied in the causal pathway to invasive neoplasia, they are already validated as predictors of cancer incidence. More attention should be paid to the quality control of SEB assays, including control of variation in cell composition of tissue samples, assay protocol, instrumentation used, and observer performance. The dose-response relationship between a known chemopreventive agent and the SEB should also be evaluated. The Division of Cancer Prevention and Control, National Cancer Institute, has begun a program to test chemopreventive agents in short-term Phase II clinical trials using dysplasia-based SEBs. The SEBs are assayed, when possible, by computerized cytometry. Trials are being conducted for oral leukoplakia, cutaneous actinic keratosis, superficial bladder cancer, pulmonary metaplasia/dysplasia, cervical dysplasia (CIN III), and adenomatous colonic polyps.
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PMID:Intraepithelial neoplasia, surrogate endpoint biomarkers, and cancer chemoprevention. 841 8

Changes in vascular patterns aid in the colposcopic diagnosis of cervical neoplasia. We have studied vessels in 50 cases of normal cervix, cervical intraepithelial neoplasia (CIN I, II, III), and invasive carcinoma by two markers, Von-Willebrand factor (VWF) and ulex europaeus lectin I. With both markers, an increase in microvessel counts parallel to neoplastic progression was seen, with highest counts observed in CIN III. Average counts for ulex lectin and VWF increased from approximately 6 vessels per field in normal cervices to 15 vessels per field in CIN III. For each diagnostic group, comparable numbers of vessels were stained by both markers, with a slight preponderance of VWF in invasive carcinomas and of ulex lectin in noninvasive lesions. No correlation was found between microvessel count and human papilloma virus (HPV) by in situ hybridization. We conclude that enhanced microvessel density occurs in cervical neoplasia. The vessels are mostly blood vessels, not lymphatics. Therefore, the role of enhanced microvessel density in tumor spread remains to be proven.
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PMID:Angiogenesis in uterine cervical intraepithelial neoplasia and squamous cell carcinoma: an immunohistochemical study. 942 Oct 72

We have shown previously that a significant number of invasive cervical cancers (ICC) have nonrandom chromosomal losses in 3p, 6p, 11q, 2q, 6q, and 19q, thereby suggesting that genes involved in the suppression of tumor development or progression are located in these regions. Cervical intraepithelial neoplasia (CIN) III is considered the precursor lesion for ICC of squamous type and occurs frequently with ICC of glandular type. In an effort to define which chromosomal losses are present in the precursor lesions, we identified CIN III lesions from 24 ICC treated by radical hysterectomy. Thirty-three CIN III associated with 22 squamous carcinomas and 2 adenocarcinomas were carefully microdissected from the paraffin-embedded sections. The whole genomic DNA from CIN III was amplified with short random primers. DNA from ICC, CIN III, and normal tissue was analyzed at the six chromosomal regions with polymorphic markers. Thirty-eight percent of hysterectomy specimens had loss of heterozygosity (LOH) in at least one of the CIN III lesions from each case. Loss occurred in 30% of cases in 3p14.1-12 (37% for associated ICC), 21% in 6p23 (33%), 14% in 2q33-37 (27%), 0 in 11q23.3 (33%), 4% in 19q13.4 (13%), and 0 in 6q21-23.3 (18%). These results suggest that mutations in 3p and 6p are important early in tumorigenesis, whereas 11q and 6q contain genes important later in tumor progression. Invasive and preinvasive cervical lesions appear to develop from multifocal genetic events since consistent losses do not occur within all precursor lesions in the same patient.
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PMID:Cervical intraepithelial neoplasia III shows frequent allelic loss in 3p and 6p. 959 35

Although genital human papillomavirus (HPV) infection is well established as the etiologic agent for cervical intraepithelial neoplasia (CIN), little is known about the cofactors involved in the development of high-grade lesions or the progression of low-grade to high-grade lesions. In our study of HPV-infected women with CIN (163 CIN I, 51 CIN II and 44 CIN III), women with CIN II or III were compared with those with CIN I for risk factors associated with high-grade lesions. After controlling for age, education, ethnicity and frequency of Pap smear screening, infection with HPV 16, but not high viral load or infection with multiple types, was associated with high-grade lesions (OR for CIN II = 11.96, OR for CIN III = 23.74). Risk of CIN III, but not CIN II, increased with number of cigarettes smoked per day (ORs = 1.49 and 3.35 for < or = 10 and > 10 cigarettes per day, respectively) and decreased with frequency of condom use during sex (ORs = 0.60 and 0.32 for women who used condoms occasionally/sometimes and most/all of the time, respectively). There were no associations between high-grade lesions and plasma levels of micronutrients (retinol, beta-carotene, alpha-tocopherol and reduced ascorbic acid). Our results indicate that infection with HPV 16 is associated with high-grade lesions. Additional cofactors, such as cigarette smoking, may be required as a carcinogen to advance HPV-infected cells toward neoplastic progression.
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PMID:HPV 16 and cigarette smoking as risk factors for high-grade cervical intra-epithelial neoplasia. 976 58

Reduced expression of the metastasis suppressor gene nm23-H1 has been previously correlated with high tumor metastatic potential and fatal clinical outcome in several types of human carcinomas. The aim of the study was to identify the expression of nm23-H1 in a variety of premalignant and malignant cervical lesions. The study comprised 106 cervical biopsies obtained from 106 women ranging in age from 23 to 68 (median 42) years. Histologic slides stained with H&E were evaluated blindly by two pathologists and a consensus diagnosis was established for each case. In addition, immunohistochemical stain was employed and a monoclonal antibody against nm23-H1 (YLEM Rome, Italy) was used. Twenty-five of the cervical biopsies showed changes of mild dysplasia (CIN I), whereas 28 demonstrated features of moderate dysplasia (CIN II) and 28 severe dysplasia (CIN III). In 25 cases infiltrating squamous cell carcinoma was identified. Expression of nm23-H1 was evident in 9/25 (36%) CIN I, 13/28 (46%) CIN II, 22/28 (78.5%) CIN III and 17/25 (68%) infiltrating carcinoma biopsies. Statistically significant differences were observed between CIN II and CIN III (p=0.003), and CIN II and infiltrating carcinoma (p=0.002) groups. Expression of the nm23-H1 gene in premalignant and malignant cervical lesions indicates that this gene may play a substantial role in carcinogenesis and tumor progression.
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PMID:Immunohistochemical analysis of nm23-H1 expression in human cervical lesions. 1119 46

We have previously demonstrated a strong relationship between loss of heterozygosity (LOH) at chromosome 11q23.3 and the presence of extensive tumor plugs in lymphvascular spaces (LVS) in stage 1B cervical carcinoma, suggesting that genes at this locus may regulate vasculoinvasion. This study examined LOH at 11q23.3 in microdissected tumor plugs within LVS and in metastatic foci in lymph nodes (MFLN), as well as corresponding invasive tumor and adjacent cervical intraepithelial neoplasia (CIN) 3 in stage 1B squamous cell carcinoma. Of 49 invasive carcinomas, 38.8% had LOH at 11q23.3. Of 36 tumor plugs in LVS, 39% had LOH at 11q23.3. Twenty percent of 15 MFLN demonstrated LOH at 11q23.3. Patients with LOH at 11q23.3 are significantly more likely to have disease recurrence than patients without LOH at 11q23.3 (P =.02). Of 10 foci of CIN 3, none showed LOH at 11q23.3. Although unlikely to have an impact early in carcinogenesis, tumor-suppressor genes located in the region of 11q23.3 appear to be important in tumor progression, facilitating lymphvascular space invasion and, by inference, spread to lymph nodes in squamous cell carcinoma of the cervix.
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PMID:Loss of heterozygosity at 11q23.3 in vasculoinvasive and metastatic squamous cell carcinoma of the cervix. 1138 64

Our objective was to review current large studies of human papillomavirus (HPV) DNA testing as an adjunct to the Papanicolaou test for cervical cancer screening programs. We analyzed 10 large screening studies that used the Hybrid Capture 2 test and 3 studies that used the polymerase chain reaction test in a manner that enabled reliable estimates of accuracy for detecting or predicting high-grade cervical intraepithelial neoplasia (CIN). Most studies allowed comparison of HPV DNA and Papanicolaou testing and estimates of the performance of Papanicolaou and HPV DNA as combined tests. The studies were selected on the basis of a sufficient number of cases of high-grade CIN and cancer to provide meaningful statistical values. Investigators had to demonstrate the ability to generate reasonably reliable Hybrid Capture 2 or polymerase chain reaction data that were either minimally biased by nature of study design or that permitted analytical techniques for addressing issues of study bias to be applied. Studies had to provide data for the calculation of test sensitivity, specificity, predictive values, odds ratios, relative risks, confidence intervals, and other relevant measures. Final data were abstracted directly from published articles or estimated from descriptive statistics presented in the articles. In some studies, new analyses were performed from raw data supplied by the principal investigators. We concluded that HPV DNA testing was a more sensitive indicator for prevalent high-grade CIN than either conventional or liquid cytology. A combination of HPV DNA and Papanicolaou testing had almost 100% sensitivity and negative predictive value. The specificity of the combined tests was slightly lower than the specificity of the Papanicolaou test alone, but this decrease could potentially be offset by greater protection from neoplastic progression and cost savings available from extended screening intervals. One "double-negative" HPV DNA and Papanicolaou test indicated better prognostic assurance against risk of future CIN 3 than 3 subsequent negative conventional Papanicolaou tests and may safely allow 3-year screening intervals for such low-risk women.
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PMID:Human papillomavirus DNA testing as an adjunct to cytology in cervical screening programs. 1287 67

Human telomerase reverse transcriptase (hTERT) and human nonmetastatic clone 23 (nm23-H1) may be separately involved in tumor progression of uterine cervix. We therefore investigate the correlations of hTERT and nm23-H1 in cervical carcinogenesis and further check their application. One hundred and twenty-eight cervical tissues, including 48 squamous cell carcinoma (SCC), 36 high-grade cervical intraepithelial neoplasia (CIN) (CIN 2 and CIN 3), 20 low-grade CIN 1, and 24 normal cases, were collected for immunohistochemical expression of hTERT and nm23-H1. Spearman rank correlation analysis was applied to assess their correlation in these samples. The Fisher exact or Chi-square test was used to evaluate the expression of hTERT or nm23-H1 among each subgroup. The sensitivity, specificity, positive and negative predictive values (PPV and NPV), and accuracy of hTERT and/or nm23-H1 were calculated for the prediction of high-grade CIN and SCC. We found normal cervix and CIN 1 samples had concurrent low expression of hTERT and nm23-H1, whereas high-grade CIN and SCC samples had concurrent high immunoreactivities. The hTERT alone and hTERT or nm23-H1 in combination had better sensitivity, NPV, and accuracy. The nm23-H1 alone as well as hTERT and nm23-H1 in combination had better specificity and PPV. Our results reveal a significantly positive relationship between expression of hTERT and nm23-H1 in normal and neoplastic tissues of uterine cervix. We suggest high expression of hTERT alone and hTERT or nm23-H1 in combination can be offered additional molecular information correlated with high-grade CIN and SCC.
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PMID:Concurrent high expression of human telomerase reverse transcriptase and human nonmetastatic clone 23 in high-grade squamous intraepithelial neoplasia and squamous cell carcinoma of uterine cervix. 1735 90


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