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PubMed2005

Diagnostic assessment of nonpalpable breast cancer--the difference in diagnostic approach for the clinical treatment of breast cancer between the Japanese Guidelines and the National Comprehensive Cancer Network(USA)Guidelines.

The detection of non-palpating breast cancer might improve the survival of patients with whole breast cancer because it can be diagnosed at an early stage. Therefore, to standardize the quality of patient care, a published assessment guideline is necessary in a clinical setting. For this purpose, Japan and USA have independent guidelines with different approaches. ''The evidence-based guideline for clinical treatment of breast cancer'' that was published in June 2005 by the Japanese breast cancer society, is the first set of integrated guidelines pertaining to breast cancer in Japan. These guidelines are presented in the research questions (RQ)format. This paper explains 7 RQs(out of 31 RQs)and also discusses the recommendations pertaining to the diagnosis of nonpalpable breast cancer. The National Comprehensive Cancer Network (NCCN; USA)guidelines, which are widely recognized as one of the most reliable guidelines based on published evidences, also contain the diagnostic assessment of asymptomatic patients with a negative physical examination. This paper discusses pros and cons of each of the above mentioned guidelines as well as their clinical application. It is necessary to use both the Japanese and NCCN guidelines while understanding the differences between the two.

Breast Neoplasms↗
PubMed1981

The molecular biology of cancer and its diagnostic implications.

The origin of cancer is discussed from the view of the two-stage model of malignant transformation. Environmental carcinogens play an integral part in the process. When the cell is transformed, cell surface changes are found for such components as fibronectin, collagen, actin, myosin, glycopeptides and enzyme activities. Hormone receptors are a fruitful line for research. Both qualitative and quantitative alterations are also seen with cancer cell enzymes. Among enzymes that can be used as markers of malignancy are the protease. A group of oncodevelopmental proteins, hormonal and non-hormonal, are in regular service for the management of cancer. Improvements in diagnostic specificity can be expected as the newer technologies are harnessed for medical use.

Carcinogens, Environmental↗
PubMed2001

Defining a test for HER-2/neu evaluation in breast cancer in the diagnostic setting.

In breast cancer amplification of the HER-2/neu oncogene and over-expression of the protein product is associated with poor prognosis, predicts response to some chemotherapeutic regimens and is the target for Herceptin treatment. To date there are several methods to assess the amplification/over-expression of HER-2/neu with each having advantages and disadvantages. We have studied amplification and over-expression of HER-2/neu in 250 consecutive cases of breast cancer (220 invasive and 30 in situ carcinomas) presenting to the Department of Pathology at Women's College Campus of Sunnybrook and Women's College Health Sciences Center. Thirty percent of the invasive carcinomas were node positive. HER-2/neu protein over-expression was assessed by immunohistochemistry (IH) using antibody CB11 and amplification of the gene by differential PCR. The percentage of tumor cells showing CB11 staining was determined and the most significant cut off point for positivity was > or =10% moderate or strong complete membranous staining. The gene was considered amplified if the density score of the product was > or =2. There was 94% concordance between the two methods (P value.0001). Both methods were positive in 16% of cases and negative in 78% of cases. Discrepant cases were examined by FISH which confirmed the IH results in 9/11 invasive carcinomas. These results show that there is excellent concordance between IH and PCR. However, immunohistochemistry is easier to perform and cheaper than PCR and could be used in routine assessment of HER-2/neu in breast cancer patients.

Breast Neoplasms↗
PubMedDate not supplied

[Roentgen diagnostics with the emphasis on it's traditional roentgenological method is a major sourse to improve gastric cancer diagnosis].

The main idea of the article is presentation of todays problem of gastric cancer diagnosis. Authors, supported by long-term experience of gastric cancer diagnostics, demonstrate the necessity of the return of traditional roentgenological method for it's diagnostics, along with endoscopic technique. In the first place it is determined by the increase of sclerotic and mixed forms. In the second place, it is associated by the change of gastric cancer primary localizations, supporting the need of active use of roentgen diagnostics for it's diagnosis. One of the important parts of the article consists of the author's attempt to change general opinion about insignificancy role of traditional roentgenological method for diagnosis of gastric cancer. Authors demonstrate modern techniques of traditional stomach roentgenology and firstly, it's digital development with CR-systems for the improvement of diagnosis of the intramural forms of carcinomas. In the initial stages it is obligatory to engage classical roentgenology with double contrast study and endoscopy as main equally important methods. The unfavourable situaition in the diagnosis of gastric cancer can be changed only with conjoint use of these two approaches. It is chiefly depends with the difficulties of endoscopic study of diffuse (endophytic) forms of gastric carcinoma. Authors separately underline the necessity of including specialists in roentgen diagnostics in the national project of modernization of roentgenological equipment in medical institutions.

Adult↗
PubMed2004

Gene expression profiling identifies platelet-derived growth factor as a diagnostic molecular marker for papillary thyroid carcinoma.

PURPOSE: Cancer diagnostics and therapeutics are often based on clinically relevant markers that are expressed specifically in a malignant tissue at levels higher than in normal tissue. We examined potential markers for papillary thyroid carcinoma (PTC) by monitoring PTC-specific gene expression using cDNA microarray. EXPERIMENTAL DESIGN: Gene expression profiles for PTC tissue, normal thyroid tissue, and healthy peripheral blood cells were compared by use of a human 4000-gene cDNA microarray. Protein expressions of the up-regulated genes in PTC were examined in thyroid tissues by immunohistochemistry. RESULTS: Sixty-four genes were overexpressed in PTC tissue relative to normal thyroid tissue and healthy peripheral blood cells. The genes that were up-regulated in PTC were involved in cell cycle regulation, DNA damage response, angiogenesis, and oncogenesis. Among these genes, basic fibroblast growth factor and platelet-derived growth factor were identified by immunochemical methods as proteins that are specifically expressed at high levels in thyroid neoplasms. Basic fibroblast growth factor, which has been identified as a biomarker for PTC, was overexpressed in 54% of PTC cases, 67% of follicular thyroid carcinomas, and 36% of benign thyroid neoplasms. Platelet-derived growth factor was overexpressed in 81% of PTC cases and 100% of follicular carcinomas, but was immunonegative in normal thyroid tissues and benign thyroid neoplasms. CONCLUSIONS: Platelet-derived growth factor may be a potential biomarker for PTC and follicular carcinoma. Expression profile analysis using a microarray followed by immunohistochemical study can be used to facilitate the development of molecular biomarkers for cancer.

Carcinoma, Papillary↗
PubMed2000

[Developments in minimally invasive breast surgery - overview and our own experience: new diagnostic and therapeutic challenges in breast cancer].

New diagnostic and therapeutic modalities in breast cancer are necessary because nowadays an increased number of suspicious breast lesions are referred to breast clinics for a histological diagnosis. In the future more than one quarter of patients might present with a preinvasive lesion and more than half of the patients will have tumors less than 2 cm. Mammography screening helps to find more preinvasive lesions. Therefore we need new tools for exact stereotactic breast biopsies in the outpatient setting, such as the advanced breast biopsy instrumentation (ABBI((R))) or the Mammotome((R)) system. For axillary clearance we need methods that lead to less morbidity. The detection of the sentinel lymph node is one of these new techniques. Endoscopic axillary clearance after liposuction also helps to reduce morbidity. Due to better visualization of the anatomic structures with axilloscopy less traumatic surgery is possible. We also combined these two new methods and described the endoscopic clearance of the sentinel lymph node in the axilla with the additional help of isosulfan blue. However, this combined method is not only time-consuming but also more expensive and shows no obvious advantage compared to the open sentinel technique. Therefore we stopped using the endoscopic sentinel technique and we now promote open sentinel lymph node biopsy without full axillary clearance when frozen section shows sentinel node-negative lymph nodes.

Axilla↗
PubMed2000

Telomerase activity in cancer as a diagnostic and therapeutic target.

Major advances have been made in understanding the role of telomerase in cellular immortalization and carcinogenesis. Human telomeres undergo progressive shortening with cell division, and critical shortening of telomeres with cellular aging triggers a signal for cells to stop dividing and senesce. Telomerase is an enzyme that adds telomeric-repeated sequences to the ends of human chromosome DNA. Telomerase is active in the vast majority of tumors, but not in normal somatic tissues, and prevents progressive shortening of telomeres with cell division, probably giving tumor cells a growth advantage over normal cells. Highly-sensitive PCR-based TRAP (telomeric repeat amplification protocol) assay provided the means to analyze telomerase in a wide variety of tissues. Evidence has been accumulated that this assay may be useful as a potential diagnostic tool for cancer. The constituents of telomerase complex have recently been identified, and human telomerase reverse transcriptase (hTERT) has been found to be responsible for the enzymatic activity of telomerase. Detection of hTERT mRNA may therefore be useful for the screening and diagnosis of cancers. The mechanisms regulating hTERT expression have been extensively analyzed, and transcriptional regulation of hTERT has been found to be essential for hTERT expression, in which several nuclear factors including c-Myc play crucial roles. Understanding of such mechanisms might provide insight into molecular basis of human carcinogenesis and contributes to the development of novel cancer gene therapy targeting telomerase.

Animals↗
PubMed2000

A case of penetrating aortic atherosclerotic ulcer with hemoptysis.

A 69-year old Japanese woman with hypertension was admitted because of continuous back pain and recurrent hemoptysis. Radiographic findings showed an enhanced irregular mass, at the aortic arch fed by the tracheal artery, which implied both a penetrating aortic atherosclerotic ulcer and lung cancer. Diagnostic surgery revealed no evidence of cancer but did reveal a rupture of the intima at the distal part of the aortic arch. It is assumed that the transmural oozing occurred after development of the penetrating aortic ulcer, which formed an extra-aortic hematoma and caused surrounding inflammation, and led to tracheal artery feeding. The intramural hematoma might have weakened vascular wall tension from the aorta, and formed an oozing extra-aortic hematoma instead of an acute rupture.

Aged↗
PubMed1985

Diagnostic tests in breast cancer. Clinical strategies based on diagnostic probabilities.

Optimal diagnostic strategies used in screening for breast cancer and evaluating breast masses depend on the likelihood of malignancy, findings at physical examination, and the accuracy of tests and procedures. Results from published series, in conjunction with calculations of the probability of malignancy based on test results, indicate that only mammography is needed for screening. A clinical sequence for evaluating palpable breast masses should include a combination of mammography, ultrasound examination, and needle aspiration. In patients with negative findings, the probability of cancer will be sufficiently low to obviate the need for immediate surgical biopsy. However, if there are positive findings, or the initial clinical likelihood of malignancy is high, excision of the mass is indicated.

Adult↗
PubMed2004

Development of new prostate specific monoclonal antibodies.

BACKGROUND: Despite the need for new prostate-specific diagnostic and therapeutic targets, very few unique prostate (cancer) specific antigens have been characterized. Monoclonal antibody (mAb) technology is a powerful tool to identify specific antigenic markers, which could be potential targets for cancer diagnostics or therapy. METHODS: Splenocytes from mice immunized with prostate cancer (PCa) homogenates of different origin were fused using standard techniques. Employing a differential high-throughput screening method followed by immediate screening in immunohistochemistry (IHC) a large number of hybridomas were screened for prostate (cancer) specificity. RESULTS: From 25 successful fusions approximately 300 clones were identified excreting PCa-reactive antibodies. Subsequent immunohistochemical fine-specificity analysis reduced this number to 26. Eventually, after extensive fine-specificity analysis, the number of mAbs appearing to define prostate-specific antigenic structures that might serve as new diagnostic or therapeutic targets was reduced to three. CONCLUSIONS: Using mAb technology combined with a high throughput screening method we have developed three mAbs (1.8, 2.26, and 3.10) directed against prostate associated antigens that might identify potential new therapeutic targets.

Animals↗
PubMed2000

[Diagnostic significance of cancer procoagulant activity in colorectal cancer].

This study aimed at evaluating diagnostic significance of cancer procoagulant (CP) activity in the homogenates of colon cancer tissues and in blood serum of patients with this neoplasm. Procoagulant activity, depending of specific cancer procoagulant, has been found in all examined tissues as well as in blood serum of cancer patients. CP activity in homogenates of colon cancer tissues as well as in blood serum of the examined cancer patients has been markedly higher than in the normal subjects. These data indicate that CP activity in the neoplastic tissue homogenates and in blood serum may be of value in the diagnosis of cancer.

Adult↗
PubMed1993

[Evaluation of tumor extension in invasive cancer of the uterine cervix. Diagnostic evaluation of cervix cancer].

Cancer of the uterine cervix accounts for approximately 30% of deaths from malignancies in gynecology and this rate has remained unchanged for more than 40 years. The most important prognostic factor is the extent of the disease at the beginning of treatment. There is, however, a discrepancy of some 50% between clinical and postoperative staging. The aim of this study was to evaluate different diagnostic investigations leading to the preoperative classification (FIGO) of 261 patients with cervical cancer. Data of presurgical clinical and radiological examinations were compared with postoperative histopathological findings. Rectovaginal palpation and computerized tomography (CAT) both showed a positive predictive value of 60%. The performance of CAT and lymphography in the diagnosis of lymph node metastasis was poor with positive predictive values of 36.3 and 20%, respectively. In the absence of parametrial infiltration on palpation, cystoscopy and rectoscopy are superfluous since they are always normal. Urography, because of the possibility to show the topographic anatomy of the urinary tract, was justified in all cases. The value of surgical staging and more recent techniques such as sonography and magnetic resonance is discussed.

Adult↗
PubMed1984

[Hypercalcemia of cancer and myeloma].

Hypercalcemia secondary to malignancies can be divided into two groups according to their calcium elevating mechanism: solid tumors with bony metastases, most frequently originating from the breast or the bronchi, and solid tumors without bony metastases, associated with secretion by the tumor of a substance which increases the calcium level. This substance resembles parathormone in pseudo-hyperparathyroidism, prostaglandins, or other substances not yet identified. The most common tumors involved are bronchial or renal cancers. Diagnostic problems vary depending on whether the cancer has been identified or not, and if bony metastases have or have not been discovered. Primary hyperparathyroidism must also be considered since it is frequently associated with cancer. Hypercalcemia from blood dyscrasias (myeloma and lymphoma) originates from the same mechanisms. It may or may not be associated with bony lesions. The hypercalcemia could be due to a "parathormone like" substance, to prostaglandins, to a substance that stimulates osteoclasts (OAF), or to calcitriol (1,25-dihydroxycholecalciferol). The treatment of hypercalcemia due to malignancies is primarily through the use of antiosteoclastic agents: calcitonin, mithramycin, and more recently diphosphonates. Corticosteroids and the prostaglandin inhibitors can have an additional calcium lowering effect.

Bone Neoplasms↗
PubMed2025

Discovery and performance of DNA methylation panels for cancer detection and classification in blood.

Examining DNA in a liquid biopsy for non-invasive cancer detection relies on identifying dilute signal in a high background. This study aims to identify DNA methylation biomarkers for multi-cancer detection. Utilizing large tissue datasets, we apply novel search algorithms to discover confined biomarker panels capable of distinguishing tumor from normal and determining the tissue of origin. We explore the applicability to blood-based testing using targeted methylation sequencing followed by machine learning classification. We present an 8-marker panel, which successfully predicts tumors across 14 types with a 91% average sensitivity, maintaining a low false positive rate (< 0.04%). Additionally, a panel of 39 CpG sites exhibits accuracies ranging from 69% to 98% for identifying tissue of origin. When tested on 114 patient plasma samples (colon, liver, pancreatic, prostate, and stomach cancer), the 8-marker panel obtains an AUC of 0.78 with a 78% sensitivity among 32 early-stage patients (stage I-II), and 60% overall. Using the 39-marker panel in a multi-class classification model selecting only the best match, 54% of tumor samples were on average correctly assigned to the tissue of origin, and up to 80% when allowing more inclusive criteria. Using a limited set of biomarkers, our work contributes to advancing non-invasive cancer diagnostics.

DNA methylation↗
PubMedDate not supplied

Application of an antibody biochip for p53 detection and cancer diagnosis.

Detection of the p53 tumor suppressor gene is important in early cancer diagnostics because alterations in the gene have been associated with carcinogenic manifestations in several tissue types in humans. We have developed an antibody-based detection instrument, the biochip, to detect the presence of the anti-p53 antibody in human serum. The design of this highly integrated detector system is based on miniaturized phototransistors having multiple optical sensing elements, amplifiers, discriminators, and logic circuitry on an IC board. The system utilizes laser excitation and fluorescence signals to detect complex formation between the p53 monoclonal antibody and the p53 antigen. Recognition antibodies are immobilized on a nylon membrane platform and incubated in solutions containing antigens labeled with Cy5, a fluorescent cyanine dye. Subsequently, this membrane is placed on the detection platform of the biochip and fluorescence signal is induced using a 632.8-nm He-Ne laser. Using this immuno-biochip, we have been able to detect binding of the p53 monoclonal antibody to the human p53 cancer protein in biological matrices. The performance of the integrated phototransistors and amplifier circuits of the biochip, previously evaluated through measurement of the signal output response for various concentrations of fluorescein-labeled molecules, have illustrated the linearity of the microchip necessary for quantitative analysis. The design of this biochip permits sensitive, selective and direct measurements of a variety of antigen-antibody formations at very low concentrations. Furthermore, the acquisitions of the qualitative and quantitative results are accomplished rapidly, in about 15 min. These features demonstrate the potential of this antibody-based biochip for simple, rapid and early biomedical diagnostics of cancer.

Antibodies, Monoclonal↗
PubMed1991

Cancer risks after diagnostic doses of 131I with special reference to thyroid cancer.

Between 1951 and 1969 a total of 35,074 patients less than 75 years of age (mean = 44 years) were examined with diagnostic doses of 131I. The mean administered activity of 131I was 52 microCi and the radiation dose to the thyroid gland was on the average of 0.5 Gy. The cohort was matched with the Swedish Cancer Register for the years 1958-1984. During this period, 3746 cancers occurred more than 5 years after the 131I examination, and the resulting standardized incidence ratio (SIR) was 1.01 (95% confidence interval [CI] = 0.98 to 1.04). SIR for thyroid cancer was 1.18 (95% CI = 0.88 to 1.56). The risks for both cancer of all sites and for thyroid cancer were highest 5 to 9 years after examination (SIR = 1.07 and 2.06, respectively) and did not differ from unity thereafter. With greater than or equal to 10 years of follow-up, risk was not statistically associated with the dose of 131I.

Adolescent↗