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The paper present the experience gained in 10 years at the consultation and diagnosis room for buccal mucosa abnormalities in Dental Health Center No. 56 in Moscow. Three cases with cancer and precancer of the buccal mucosa and red lips detected in this room are described.
Cancer screening by definition as an organized effort to detect cancer at an early stage when reduced mortality is possible. Cancer screening should not be the exclusive responsibility of comprehensive cancer centers or large urban medical centers. Rather, every health professional should play a significant role in the early detection and education of patients with cancer. As seen here, some of the most common and life-threatening forms of cancer are the most preventable. Practical and inexpensive steps exist for thorough and effective screening. Nurses educated in the early detection of cancer are in a unique position; they are on the front line of patient care in the promotion and education of patients to the many benefits of early detection. Preventive efforts, such as screening and early detection, coupled with vastly improved treatment modalities, provide a very real and potent weapon against diseases that only 20 years ago were considered incurable.
PURPOSE: Aberrant promoter hypermethylation of Wnt-antagonist genes contributes to the pathogenesis of several cancers. We hypothesized that combined methylation analysis of Wnt-antagonist genes could improve their use as a panel of biomarkers for diagnosing and staging of bladder cancers. EXPERIMENTAL DESIGN: Samples (54 total) of bladder tumor and corresponding normal bladder mucosa were analyzed for the methylation and expression levels of six Wnt-antagonist genes (sFRP-1, sFRP-2, sFRP-4, and sFRP-5, Wif-1, and Dkk-3). To increase the sensitivity/specificity of bladder tumor detection, the methylation score (M score), a new method for multigene methylation analysis, was developed. The M score of each sample was calculated as the sum of the corresponding log hazard ratio coefficients derived from multivariate logistic regression analysis of the methylation status for each Wnt-antagonist gene. Receiver operator characteristic (ROC) curve analysis was used to determine the optimal sensitivity/specificity of the M score. Urine DNA from 24 matched patients with bladder tumor and 20 cancer-free volunteers was also used to investigate the methylation status of Wnt-antagonist genes. RESULTS: The methylation levels of Wnt-antagonists were significantly higher and mRNA levels were significantly lower in bladder tumor than in bladder mucosa. Each methylation level was inversely correlated with the corresponding mRNA level. In multivariate regression analysis, the methylation levels of sFRP-2 and Dkk-3 were significant independent predictors of bladder tumor (P < 0.05 and P < 0.01, respectively), whereas with sFRP-1, sFRP-5, and Wif-1 there was a trend towards significance as independent predictors. The M score of Wnt-antagonist genes was significantly higher in bladder tumor than in bladder mucosa (P < 0.05). Overall, the M score had a sensitivity of 77.2% and a specificity of 66.7% as a diagnostic biomarker (areas under the curve, 0.763). The M score could distinguish superficial from invasive bladder tumors with a sensitivity of 72.2% and a specificity of 61.1% as a staging biomarker (areas under the curve, 0.671). In patients with bladder tumor, 80.6% of the methylation-specific PCR results had identical methylation in samples of tumor- and urine-derived DNA. Most urine DNA in normal controls showed no aberrant methylation of the Wnt-antagonist genes. CONCLUSIONS: Hypermethylation of Wnt-antagonist genes plays an important role in the pathogenesis of bladder tumor and can be detected using cellular DNA extracted from urine samples. This is the first report demonstrating that M score analysis of Wnt-antagonist genes could serve as an excellent epigenetic biomarker panel for bladder tumors.
BACKGROUND: Limited data are available on the genetic events underlying gastric cancer. Studying a few cases by conventional cytogenetic techniques, we previously reported that chromosome 8 might be frequently involved. The aim of our study was to evaluate the numerical aberrations of chromosome 8 in gastric cancer using fluorescence in situ hybridization (FISH). MATERIALS AND METHODS: FISH, with an a-satellite DNA probe specific for chromosome 8, was applied to 37 primary gastric tumors directly processed for cytogenetic study. RESULTS: Numerical aberrations of chromosome 8 were observed in 23 out of 37 tumors (62.16%). Trisomy was detected in 16 cases (43.24%), tetrasomy in 4 cases (10.81%) and monosomy in 3 cases (8.10%). No correlation was found between polysomy 8 and the histopathologic characteristics of the tumors. CONCLUSION: An increase in the number of chromosome 8 may frequently occur in gastric cancer. Advanced and more aggressive gastric tumors did not harbor polysomy 8. Further studies at molecular and clinical level must be carried out to identify the gene alterations reflected by polysomy 8 and possibly to facilitate the detection of specific tumors subtypes.
Gene amplification is clearly an important aspect of tumour growth and development and has prognostic significance in certain tumours. The identification and genetic characterisation of new areas of amplification in human malignancy remains an important goal in understanding the underlying genetic lesions within these tissues. In the present work, arbitrarily primed-PCR (AP-PCR) has been applied to detect and characterise amplified DNA fragments in human non small cell lung cancer (NSCLC). Our results show that gains of genomic sequences occur at high frequency (64% of all genomic changes analysed). Moreover, we succeeded in detecting a genomic sequence that is highly amplified in one of the tumours analysed. The amplification intensity of this DNA fragment was also increased in 29 (45%) of the 65 NSCLC patients from our study. The amplified DNA fragment was isolated and identified as a 600 bp sequence mapped to chromosome 6p12. This sequence did not show significant homology with known human DNA sequences. Interestingly, a gene related to cancer processes, the pim-1 oncogene, is placed neighbouring to this region on chromosome 6. Survival studies revealed that disease-free interval of NSCLC patients was shorter in patients bearing the amplified sequence (p = 0.05 by the Breslow test). Our findings suggest that the amplified sequence located on chromosome 6 might be relevant in the pathogenesis of human NSCLC. Int. J. Cancer (Pred. Oncol.), 84:344-349, 1999.
PROBLEM BEING ADDRESSED: Colorectal cancer (CRC) is a substantial cause of death and morbidity in Canada. Endoscopy screening by colonoscopy has been recommended, but widespread implementation is impossible because it is difficult to obtain, especially in rural areas. OBJECTIVE OF PROGRAM: To screen for CRC safely and effectively using colonoscopy performed by non-specialist endoscopists in rural areas. PROGRAM DESCRIPTION: Health providers and community organizations were informed about the screening program. Patients between the ages of 50 and 75 and those at high risk of CRC based on family history were screened. Measures of safety and effectiveness were monitored. In 2 years of screening, one of 152 patients was found to have CRC, and 23.7% had adenomatous polyps. There were no complications. Rates of CRC and adenoma detection and cecal intubation were similar to rates found in other screening studies. CONCLUSION: It was not difficult to design and implement a CRC screening program in our small rural community. Colonoscopies performed by family physicians have been effective, and there have been no serious complications.
BACKGROUND: A cohort of 51 consecutive patients with roentgenographically occult lung cancer, identified by sputum cytology and confirmed by bronchoscopy was reported previously. METHODS: All patients have now been followed beyond 5 years and the causes of death ascertained. RESULTS: The actual 5-year survival of 27 patients who were resected for cure was 74% including death for all causes. The 5-year survival of all patients who received either surgery or radiation in an attempt to cure was 54.3%. Twelve secondary cancers were found by sputum cytology; eight of these patients have died. CONCLUSIONS: Sputum cytology can be useful in the identification of early stage lung cancer in patients at high-risk where the chances of cure are favorable.
Pancreatic cancer is characterized by an increasing incidence and an extremely poor prognosis. It is resistant to most of the conventional treatment modalities. Histomorphologically, it presents with a strong desmoplastic reaction around cancer cells, and lymphocytes are typically localized as aggregates in the fibrotic interstitial tissue. Using the method of multi-epitope imaging with fluorochrome-tagged specific MoAbs which allows the simultaneous localization and characterization of T cells in tissues, we studied phenotypes and distribution of tumour-infiltrating lymphocytes (TIL) in pancreatic cancer. CD3+ T cells comprised up to 90% of the tumour-infiltrating cells which were either CD4+ or CD8+, most of them being memory cells (CD45RO+). In decreasing order of frequency, T lymphocytes carried the markers for CD45RO, CD18, CD103 and TCR gammadelta. Very few natural killer cells (CD56+) were observed. Twenty percent of CD8+ were labelled with CD103. These CD8+CD103+ T cells, analogous to the gut intraepithelial lymphocytes (IEL), were found in the fibrous interstitial tissue. Furthermore, an inverse correlation was found between the expression of CD18, the beta2-integrin, which mediates adhesion of activated lymphocytes, and CD45RO in the CD8+ subset of TIL (P = 0.046). In conclusion, phenotyping of T lymphocytes in pancreatic cancer raises the possibility that pancreatic cancer cells develop several strategies to escape the T cell-induced cytolysis by (i) the aggregation of cytotoxic CD8+CD103+ T cells in the fibrous tissue distant from the tumour cells, and (ii) the presence of CD18-bearing cells which lack the expression of the activation marker CD45RO.
Use of mammography in asymptomatic women does discover breast cancer at an earlier point in development, as measured by size, invasiveness, and nodal involvement. The integration of mammography into routine periodic evaluation of asymptomatic women over 35 years of age should diminish the threat of breast cancer.
In this study, breast cancer knowledge, beliefs and practices in low income black women were examined. First, focus groups were held with a total of 33 participants. Information gathered from the focus groups was used to develop a telephone survey which was partially based on the Health Belief Model (HBM) and administered to 92 subjects. Utilization rates of mammography and breast self-examination (BSE) were quite high; 66.3% of survey participants reported having at least one mammogram and 72.5% performed BSE. Because low-cost mammograms were available to the survey participants, these results suggest that women in this target population will utilize accessible and affordable mammograms. Several knowledge deficiencies that need to be addressed were also identified. Most of the health beliefs were not significantly associated with mammography or BSE utilization. Because the HBM has never been extensively tested on this population, its appropriateness as a behavior model for low-income women is examined. Implications for future research and interventions are discussed.
Peripheral blood leukocytes from patients with gastric cancer and various other malignant and nonmalignant diseases and peripheral blood leukocytes from apparently healthy volunteers were tested in the leukocyte migration inhibition test with the use of 4-5 different 3 M KCl extracts of gastric cancer tissue. An operational criterion for defining sensitization of patients' leukocytes was developed; i.e., evidence in an individual sample of leukocytes of either decreased or increased migration areas (migration index less than or equal to 0.79 and larger than or equal to 1.20, respectively) with 3 or more antigen extracts. With this as an indicator of sensitization, it was found that 91% of patients with gastric cancer (39/43), comparto 5% (5/94) and 3% (1/32) of patients with nonmalignant, nongastric diseases and normal controls, respectively, were reactive. Patients with various nongastric cancers were sensitized in 36% (49/135) of cases. Gastritis and gastric, as well as duodenal, ulcer did not influence the reactivity of patients' leukocytes, but considerable sensitization was found in patients with atrophic gastritis or intestinalization. When classified in the usual manner, i.e., by considering the reaction with individual tumor extracts, the specificity and the sensitivity of the test was markedly diminished: More false negative determinations were found in the group of gastric cancer patients, and the percentage of false positives in the group of nonmalignant diseases increased. The results gave evidence of tumor-associated antigens in gastric cancer patients, against which the host elicited a cellular immune response. The high incidence of positive reactivity of leukocytes from patients with gastric cancer, together with the considerable cross-reactivity of leukocytes from patients with nongastric cancer, pointed to the expression of antigens with organ-related and widespread specificities.
CT has recently been used in mass screening for lung cancer. Small cancers have been identified but the growth characteristics of these lesions are not fully understood. We identified 82 primary cancers in our 3-year mass CT screening programme, of which 61 were examined in the present study. The volume doubling time (VDT) was calculated based on the exponential model using successive annual CT images or follow-up CT images. All cases were also examined in the hospital by high resolution CT (HRCT). Lesions were divided into three types based on HRCT characteristics: type G (n = 19), ground glass opacity (GGO); type GS (n = 19), focal GGO with a solid central component; and type S (n = 23), solid nodule. 18 (95%) lesions of type G, 18 (95%) of type GS and 7 (30%) of type S were invisible on conventional chest radiographs. The mean size of the tumour was 10 mm, 11 mm and 16 mm for type G, type GS and type S, respectively. Most tumours (80%) were adenocarcinomas; 78% of these were GGO (type G and GS). Mean VDT values were 813 days, 457 days and 149 days for type G, type GS and type S, respectively; these are significantly different from each other (p < 0.05). Our results show that annual mass screening CT for 3 successive years resulted in the identification of a large number of slowly growing adenocarcinomas that were not visible on chest radiographs.
BACKGROUND: Complementary DNA array analysis of gene expression has a potential application for clinical diagnosis of disease processes. However, accessibility, affordability, reproducibility of results, and management of the data generated remain issues of concern. Use of cDNA arrays tailored for studies of specific pathways, tissues, or disease states may render a cost- and time-effective method to define potential hallmark genotype alterations. MATERIALS AND METHODS: We produced a 332-membered human cDNA array on nylon membranes tailored for studies of angiogenesis and tumorigenesis in reproductive disease. We tested the system for reproducibility using a novel statistical approach for analysis of array data and employed the arrays to investigate gene expression alterations in ovarian cancer. RESULTS: Intra-assay analysis and removal of agreement outliers was shown to be a critical step prior to interpretation of cDNA array data. The system revealed highly reproducible results, with intermembrane coefficient of reproducibility of +/- 0.98. Comparison of placental and ovarian sample data confirmed expected differences in angiogenic profiles and tissue-specific markers, such as human placental lactogen (hPL). Analysis of expression profiles of five normal ovary and four poorly differentiated serous papillary ovarian adenocarcinoma samples revealed an overall increase in angiogenesis-related markers, including vascular endothelial growth factor (VEGF) and angiopoietin-1 in the diseased tissue. These were accompanied by increases in immune response mediators (e.g. HLA-DR, Ron), apoptotic and neoplastic markers (e.g. BAD protein, b-myb), and novel potential markers of ovarian cancer, such as cofilin, moesin, and neuron-restrictive silencer factor (REST) protein. CONCLUSIONS: In-house production of tailored cDNA arrays, coupled to comprehensive analysis of resulting hybridization profiles, provides an accessible, reliable, and highly effective method of applying array technology to study disease processes. In the ovary, abundance of specific tumor markers, increased macrophage recruitment mediators, a late-stage angiogenesis profile, and the presence of chemoresistance-related markers distinguished normal and advanced ovarian cancer tissue samples. Detection of such parallel changes in pathway- and tissue-specific markers may prove a hallmark ready for application in reproductive disease diagnostic and therapeutic developments.
Early diagnosis of breast cancer using breast examination, mammography and ultrasonography is highly accurate, but radiologically dense breast represent a challenge for the mammographic detection of early stage tumors. The aim of this study is to determine the clinical value of scintigraphic techniques in the early diagnosis of breast cancer when other methods give non-conclusive results. The study includes 160 women with clinical suspicion of breast cancer and non-conclusive findings in mammography, randomized either to scintigraphic scans with Sestamibi Tc 99m or Tl 201. Up to date, 64 women have been enrolled, 46 in Tl-201 and 18 in Sestamibi Tc 99m. Results obtained show 73% sensitivity and 94% specificity with Tl 201 and 77% sensitivity and 100% specificity with Sestamibi Tc 99m. In this group, diagnostic accuracy improves when the tumors are bigger than two centimetres in diameter or when they are palpable. These preliminary results show that scintigraphic breast examination seems useful when other diagnostic methods provide non-conclusive results.
A small sodium iodide scintillation detector was designed for insertion through a fiberoptic bronchoscope to detect and localize sites of deposition of cobalt-57 bleomycin in lung cancer. The detector was used in 40 diagnostic studies of 34 patients; 21 of the patients had tumors. We compared the sensitivity, specificity, accuracy, and predictive value of the detector to those of plain chest x-ray films and bronchoscopy in detecting tumors. Sensitivity and specificity for the detector were 68 percent and 80 percent, respectively; for bronchoscopy, 72 percent and 100 percent; and for roentgenograms, 80 percent and 53 percent. Sensitivity for the detector and bronchoscopy combined was 92 percent. The detector succeeded in locating nonvisible submucosal and extraluminal tumors, and may contribute to early diagnosis and more accurate staging of lung cancer.
Mutations in the tumor-suppressor p53 gene TP53 are frequent in most human cancers including breast cancer. A new solid phase chemical cleavage of mismatch method (CCM) allowed rapid and efficient screening and analysis of the TP53 gene in DNA samples extracted from tumors of 89 breast cancer patients. The novel CCM technique utilized silica beads and the potassium permanganate/tetraethylammonium chloride (KMnO(4)/TEAC) and hydroxylamine (NH(2)OH) reactions were performed sequentially in a single tube. Mutation analysis involved amplification of five different fragments of the TP53 gene using DNA from the 89 tumor samples, then pairing of the 391 labeled PCR products and forming heteroduplexes. A total of 41 unique signals were revealed in the analysis of TP53 exons 5-9 and eight were identified by direct sequencing. The three novel mutations detected are c.600T>G (p.Asn200Lys), c.601T>G (p.Leu201Val), and c.766-768delACA (p.Thr256del). The detected mutations c.638G>T (p.Arg213Leu), c.730G>T (p.Gly244Cys), and c.758C>T (p.Thr253Ile) have not been reported in breast cancer but have been recorded in tumors of other organs. A previously reported mutation c.535C>T (p.His179Tyr) and a heterozygous polymorphism c.639A>G were also detected. Of the 41 unique signals, 36 were not identified as a sequence change. As direct sequencing requires the mutant allele concentration to be greater than 30% when the mutant allele is present in a mixture with the wild-type allele, the CCM method represents a more sensitive technique requiring a lower mutant allele concentration in the wild-type mixture compared with direct sequencing. This reveals the advantage of CCM for unknown point mutation detection in DNA samples of cancer patients.
OBJECTIVE: To investigate the relationship between interphase cytogenetics and the grade and stage of bladder cancer in patients with transitional cell carcinomas of the urinary bladder. PATIENTS AND METHODS: By use of in situ hybridization with chromosome-specific DNA probes, the copy number of pericentromeric sequences on chromosomes 7, 10, 11, 17, 18, X and Y was detected within interphase nuclei in formalin-fixed and paraffin-embedded sections of the routinely processed bladder cancers from 20 patients. The percentage of hyperdiploid cells (three or more spots) was estimated using light microscopy. RESULTS: The percentage of hyperdiploid cells for chromosomes 7, 11 and 17 was highly correlated with increasing tumour grade (P < 0.01, Spearman rank correlation) or increasing pathological stage (P < 0.01). The percentage of hyperdiploid cells for chromosome Y was not correlated with either grade or stage (P > 0.05). As high tumour grade and stage are both indicative of more aggressive tumour behaviour and a worse prognosis, these findings suggest that the percentage of hyperdiploid cells, especially for chromosomes 7, 11 and 17, may be highly predictive of bladder tumour aggressiveness. CONCLUSION: These preliminary results suggest that measurement of numerical chromosome aberrations using in situ hybridization in bladder cancer may offer a new objective and quantitative assay of the biological potential of individual tumours.
DNA in situ hybridization techniques for cytogenetic analyses of human solid cancers are nowadays widely used for diagnostic and research purposes. The advantage of this methodology is that it can be applied to cells in the interphase state, thereby circumventing the need for high-quality metaphase preparations for karyotypic evaluation. In situ hybridization (ISH) with chromosome specific (peri)centromeric DNA probes, also termed "interphase cytogenetics", can be used to detect numerical changes, whereas comparative genomic hybridization (CGH) discloses chromosomal gains and losses, i.e. amplifications and deletions. We wanted to compare both methods in human solid tumors, and for this goal we evaluated ISH and CGH within a set of 20 selected prostatic adenocarcinomas. Chromosomes 7 and 8 were chosen for this analysis, since these chromosomes are frequently altered in prostate cancer. ISH with chromosome 7 and 8 specific centromeric DNA probes was applied to standard, formalin-fixed and paraffin-embedded, histological sections for numerical chromosome analysis. CGH with DNA's, extracted from the same histologic area of the archival specimens, was used for screening of gains and losses of 7 and 8. ISH with centromeric probes distinguished a total of 26 numerical aberrations of chromosome 7 and/or 8 in the set of 20 neoplasms. In the same set CGH revealed a total of 35 losses and gains. CGH alterations of 7 and 8 were seen in twenty-two of the 26 chromosomes (85%) that showed aberrations in the ISH analysis. Concordance between ISH and CGH was seen in 11 (of 26; 42%) chromosomes. Eight chromosomes were involved in gains (5 x #7, 3 x #8), three in losses (3 x #8). This included both complete (3/11) and partial (8/11) CGH confirmation of the numerical alteration. Partial CGH confirmation was defined as loss or gain of a chromosome arm with involvement of the centromeric region. In the majority of these cases it concerned a whole chromosome arm, mostly the long arm. We conclude that generally a fair correlation was found between ISH and CGH in interphase preparations of a series of prostate cancers. However, when specified in detail, most of the numerical ISH aberrations were only partly represented in the CGH analysis. On the one hand, it suggests that CGH does not adequately discriminate numerical abnormalities. On the other hand, it likely implies that not all numerical changes, as detected by interphase cytogenetics, are truly involving the whole chromosome. A part of these discrepancies might be caused by structural mechanisms, most notably isochromosome formation.