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Differential expression of the early lung cancer detection marker, heterogeneous nuclear ribonucleoprotein-A2/B1 (hnRNP-A2/B1) in normal breast and neoplastic breast cancer.

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2/B1) is highly expressed during critical stages of lung development and carcinogenesis. To determine if the expression of hnRNP-A2/B1 is an informative biomarker in breast carcinogenesis, we analyzed hnRNP-A2/B1 overexpression by immunohistochemistry in archived specimens. Expression was detected in 48/85 (56.5%) primary invasive breast cancers and 7/72 (9.7%) specimens of normal breast tissue. Northern analysis of breast cancer cells also demonstrated higher level of hnRNP-A2/B1 expression compared to normal or transformed breast cells. Expression of hnRNP-A2/B1 in breast cancer cells was decreased by exposure to retinoids coordinately with decreased cell growth. These results warrant further evaluation of hnRNP-A2/B1 as a marker of breast carcinogenesis.

Biomarkers, Tumor↗

Low serum ferritin levels as a clue to colonic cancer detection in two patients with coronary artery disease: a case report.

We diagnosed colonic cancer using low serum ferritin levels as a clue in two patients with cardiac or cardiopulmonary disease. In the course of the follow-up, the serum ferritin levels decreased to less than 18 ng/mL without significant appearance of iron-deficiency anemia. One patient showed positive immunological fecal occult blood test results whereas the other not. Both patients rejected further colonoscopy because of their concern for stress in relation to their cardiac or cardiopulmonary diseases, but instead agreed to positron emission computed tomography (PET) using a F-18 deoxyglucose at their own expense. In both patients, PET documented abnormal tracer accumulation in the colon. From the results of PET imaging, they eventually agreed to colonoscopy. A colonic adenocarcinoma was detected at the site of the positive PET finding in each patient. Both patients underwent curative resection of the cancer. The detection of the levels of serum ferritin may be available for the screening colonic cancer in patients declining colonoscopic examination.

Adenocarcinoma↗

The biology of head and neck cancer. Detection and control by parallel histologic sections.

Microscopic fingers of epidermoid cancer can extend submucosally 1 to 3 cm from grossly discernible borders of upper aerodigestive tract cancers. These fingers are best detected by sectioning all surgical margins parallel to the margins. Microscopic disease was found at the original excisional margins in 75% of 70 cases. Using this principle for frozen-section evaluation, and reexcising further tissue as indicated, local disease was completely controlled in all 24 patients eligible for two-year follow-up.

Carcinoma, Squamous Cell↗

Skin cancer detection and prevention: a community program promoting sun safe behaviors.

New cases of skin cancer will be diagnosed over one million times in the United States in 1999. Basal and squamous cell types can cause significant cosmetic morbidity. Malignant melanoma can cause serious morbidity and mortality. Thus, early detection and prevention efforts are crucial for all skin cancers. Studies have identified genetic, hereditary, and environmental factors associated with increased risk of developing skin cancer. In this article, the incidence and risk factors are reviewed. The Howard County Skin Cancer Awareness Project, established in 1996, is presented as a community based program that aims to increase public awareness about the prevention and early detection of skin cancer. Future directions are also addressed.

Basal Cell Carcinoma↗

Advancing cancer detection and treatment using longitudinal routine clinical data.

Cancer management remains fragmented across its continuum, from late-stage diagnosis and salvage therapies to non-personalized surveillance. Here, we present Oncoformer, a unified multimodal transformer model trained on the China Oncology Multimodal Prediction and Surveillance Study (COMPASS) cohort (3.67 million individuals, 17.7 million clinical visits) and validated on independent external cohorts, including the UK Biobank. Oncoformer integrates longitudinal electronic health records with chest X-ray imaging to address multiple clinical tasks: pan-cancer diagnosis (area under the receiver operating characteristic curve [AUROC] = 0.956), future cancer prediction up to 1 year before diagnosis (AUROC = 0.869), tumor stage inference (mean AUROC > 0.90), patient-specific treatment-response forecasting, and recurrence-free survival stratification across ten cancer types (all p < 0.01). Staging predictions were independently validated against postoperative pathological endpoints and shown to converge on core cancer genomic pathways. By translating routine clinical data into a dynamic view of cancer evolution, Oncoformer provides a framework for risk-informed cancer prediction and treatment stratification using routine clinical data.

Humans↗

Repeat screening for prostate cancer after 1-year followup in 984 biopsied men: clinical and pathological features of detected cancer.

PURPOSE: We describe the yield of a repeat examination and biopsy procedure 1 year after initial biopsy was negative. We also assessed the parameters responsible for the failure to diagnose these cancers at the primary screening. MATERIALS AND METHODS: We screened 8,103 men randomized to the screening arm of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer using prostate specific antigen measurement, digital rectal examination and transrectal ultrasound. At the primary screening biopsy of 1,875 men was positive for prostate cancer in 374. Of the remaining 1,501 men 984 underwent repeat screening. RESULTS: Biopsy at repeat screening diagnosed prostate cancer in 49 of 442 men (11%), a rate significantly lower than the 19.9% true positive biopsy rate at the primary screening. Pathological characteristics of the tumors diagnosed were not significantly different in the 2 groups. However, prostate volume in men diagnosed with prostate cancer was significantly greater at repeat versus primary screening (mean 42.6 versus 34.9 cc, p = 0.003). The clinical characteristics were more favorable because of an increased proportion of stage T1C tumors. Prostate volume in men with stage T1C cancer was significantly greater than in those with palpable or visible tumors in whom prostate specific antigen values were in the same range. CONCLUSIONS: The most important factor responsible for the failure to diagnose these cancers at the primary screening was significantly greater prostate volume. Tumor characteristics were not significantly different in the groups. If prostate cancer screening were to become a routine health care policy, efforts would have to be made to improve the chances of diagnosing prostate cancer in larger prostates by repeat biopsy or by increasing the number of cores obtained.

Aged↗

Bladder cancer detection with urinary survivin, an inhibitor of apoptosis.

The current "gold standard" for the diagnosis of bladder cancer is cystoscopy and urine cytology. Cystoscopy, a naked eye assessment of the bladder, is invasive, uncomfortable and costly while cytology has high specificity but low sensitivity (40-60%) particularly for low-grade lesions. Therefore, there is a need for a molecular tumor marker assay that is simple to perform and sensitive, particularly for low-grade lesions. By looking to the pathophysiology of bladder cancer, we identified survivin, an inhibitor of apoptosis that is not generally expressed in fully differentiated adult tissue and is highly expressed in bladder cancer. Survivin is detected in whole urine of patients with TCC using a simple antibody based test. The sensitivity of survivin testing for new or recurrent bladder cancer is 100% while the specificity for other neoplastic and non-neoplastic genitourinary disease is 95%. The high sensitivity of this simple, noninvasive test is well suited to bladder cancer, a disease with high rates of recurrence.

Apoptosis↗

Cancer-specific genomic instability in bronchial lavage: a molecular tool for lung cancer detection.

We examined genomic instability in DNA from 80 bronchial lavage samples from patients with lung cancer and individuals with no malignant lung disease. We used a multiplex assay of eight fluorescent-tagged microsatellite markers that have a very high incidence of allelic imbalance in lung tumors. When genomic instability at individual loci was analyzed statistically against diagnosis, markers D3S1289 (P = 0.033), D3S1300 (P = 0.001), D13S171 (P = 0.009), and D17S2179E (P = 0.017) demonstrated significantly higher frequency of instability in bronchial lavage specimens from lung cancer cases than those with nonmalignant conditions. In contrast, markers D9S157, D9S161, D13S153, and D5S644 demonstrated lower specificity (P > 0.05) for lung tumors. These results suggest that genomic instability in some loci may be related to high proliferation rates but not necessarily to cell commitment to malignancy. When genomic instability was scored with only the four cancer-specific markers, the assay produced a sensitivity of 73.9% and a specificity of 76.5%. On combining the results from the cytological examination and the molecular assay, the sensitivity reached 82.6%. These results indicate that in our efforts to investigate genomic instability as a potential marker for the early detection of lung cancer, we need to identify cancer-specific genomic instability markers. This paper has shown that these first four markers may be considered to form an individual set of cancer-specific genomic instability markers.

Adult↗

The DNA-instability test as a specific marker of malignancy and its application to detect cancer clones in borderline malignancy.

Recent progress in cytogenetic and biochemical mutation assay technologies has enabled us to detect single gene alterations and gross chromosomal rearrangements, and it became clear that all cancer cells are genetically unstable. In order to detect the genome-wide instability of cancer cells, a new simple method, the DNA-instability test, was developed. The methods to detect genomic instability so far reported have only demonstrated the presence of qualitative and quantitative alterations in certain specific genomic loci. In contrast to these commonly used methods to reveal the genomic instability at certain specific DNA regions, the newly introduced DNA-instability test revealed the presence of physical DNA-instability in the entire DNA molecule of a cancer cell nucleus as revealed by increased liability to denature upon HCl hydrolysis or formamide exposure. When this test was applied to borderline malignancies, cancer clones were detected in all cases at an early-stage of cancer progression. We proposed a new concept of "procancer" clones to define those cancer clones with "functional atypia" showing positivities for various cancer markers, as well as DNA-instability testing, but showing no remarkable ordinary "morphological atypia" which is commonly used as the basis of histopathological diagnosis of malignancy.

Animals↗

Thomsen-Friedenreich and Tn antigens in nipple fluid: carbohydrate biomarkers for breast cancer detection.

PURPOSE: Novel biomarkers would facilitate early and accurate diagnosis of breast cancer. The Thomsen-Freidenreich (TF) and Tn antigens are aberrantly glycosylated carbohydrate cancer-associated antigens found in approximately 80% of adenocarcinomas. Both TF and Tn are expressed on cell-surface glycoproteins and glycolipids. Nipple aspirate fluid (NAF) is concentrated in secreted proteins and lipids from cells that give rise to cancer. The objective of this study was to determine if NAF from breasts with cancer contains elevated levels of TF and Tn compared with NAF from normal breasts. A sensitive and specific antigen capture immunoassay for TF and Tn detection in NAF was developed for this purpose. EXPERIMENTAL DESIGN: Fifty NAF samples, 25 from breasts with cancer and 25 from normal breasts, were examined. Antigen capture immunoassays were done on the samples using monoclonal antibodies that specifically recognized either TF or Tn antigen in NAF. These antibodies captured serially diluted NAF samples, and the concentration of TF or Tn was determined by comparing absorbance values against a standard curve generated from standard sources of TF or Tn. RESULTS: TF and Tn were detected in 19 of 25 and 20 of 25 NAF samples from breasts with cancer, respectively, compared with 0 of 25 and 1 of 25 NAF samples from breasts without cancer (P < 0.001 for both TF and Tn). In 92% of the cancerous breast NAF samples tested, either TF or Tn was found. CONCLUSIONS: Simultaneous measurement of TF and Tn in NAF may facilitate the noninvasive detection of breast cancer and warrants further study.

Adult↗

Microsatellite analysis of fecal DNA for colorectal cancer detection.

BACKGROUND AND OBJECTIVES: The advent of noninvasive methods of testing for colorectal cancer that have a high level of specificity and sensitivity is eagerly awaited. METHODS: Thirty patients with sporadic colorectal cancer and 11 patients with hereditary nonpolyposis colon cancer (HNPCC) enrolled in this study. We analyzed the loss of heterozygosity (LOH) in matched genomic DNA extracted from blood and surgical specimens (tumor and tumor-free colonic mucosa), and the corresponding oral rinse and stool specimens using seven microsatellite loci (APC, p53, DCC, hMLH1, D9S162, D9S171, and IFNA). To reduce the normal colonocyte DNA contamination of the stool samples, we compared three different methods for fecal genomic DNA extraction. As normal controls, we analyzed the LOH using the oral rinse and stool samples from 15 individuals without cancer. RESULTS: The LOH determined from the oral rinse and the stool samples matched those determined from the blood and the neoplastic tissue. All patients with HNPCC had microsatellite alterations at hMLH-1 in tumor DNA and corresponding fecal DNA. There were significant differences in the frequency of p53-LOH and D9S171-LOH between the group with sporadic disease and those with HNSCC (P = 0.0031 and 0.0294, respectively). Two cases with D9S162-LOH were detected in individuals without cancer. For the patients with sporadic disease, using p53 and adenomatous polyposis coli (APC), the sensitivity of the fecal DNA analysis was 96.7% (95% CI, 83-100) with a specificity of 100%. CONCLUSION: We demonstrate that LOH analysis using oral rinse and stool samples may be a suitable screening tool for colorectal cancer.

Aged↗

Free / total prostate specific antigen ratio for prostate cancer detection: a prospective blind study.

BACKGROUND: We conducted this prospective study to evaluate the ability of the percentage of free PSA (% fit PSA) to improve the specificity of prostate cancer (PC) detection. MATERIALS AND METHODS: Seven hundred and eighty-five patients with serum PSA levels between 4 and 25 ng/ml underwent sextant biopsies of the prostate. The % f/t PSA was analyzed for the sensitivity, specificity and positive predictive values. RESULTS: The mean % f/t PSA of the 169 patients with PC was 18.0 +/- 7.7 and was significantly (p < 0.0001) lower than that of the 616 patients who had histologically benign biopsy specimens, with a mean % f/t PSA of 26.6 +/- 9.7. Using 30% f/t PSA as the cut-off eliminated 34.4 % of the negative biopsies while still detecting 93.4% of the carcinomas. CONCLUSION: The optimal cut-off value of 30% f/t PSA may be applied as reference using the Cis bio international assay for PC detection.

Adult↗

High concordance of gene methylation in post-digital rectal examination and post-biopsy urine samples for prostate cancer detection.

PURPOSE: We evaluated the concordance between post-digital rectal examination and post-prostate biopsy urine samples using conventional methylation specific polymerase chain reaction analysis of 3 gene promoters in patients with suspected or confirmed prostate cancer. MATERIALS AND METHODS: Voided urine specimens were collected from 17 men after 15-second digital rectal examination and again after transrectal ultrasound guided biopsy of the prostate for suspected malignancy or for followup biopsy as part of an expectant management protocol. Urine sediment DNA was isolated and subjected to bisulfite modification. Methylation of GSTP1, EDNRB and APC promoters was determined by conventional methylation specific polymerase chain reaction analysis in post-digital rectal examination and post-biopsy samples, and correlated with clinical information. RESULTS: Prostate cancer was detected on prostate biopsy in 12 of 17 patients (71%). Promoter methylation was detected in post-digital rectal examination urine specimens for GSTP1 (24%), APC (12%) and EDNRB (66%). Promoter methylation was detected in post-biopsy urine specimens for GSTP1 (18%), APC (18%) and EDNRB (77%). The concordance between post-digital rectal examination and post-biopsy urine samples was 94% for GSTP1 and APC, and 82% for EDNRB. Overall 100% of patients with biopsy proven prostate cancer had at least 1 gene methylated in urine vs 60% of those without evidence of prostate cancer on biopsy. CONCLUSIONS: Gene analysis using conventional methylation specific polymerase chain reaction is a reliable method for detecting abnormal DNA methylation in voided urine samples obtained following digital rectal examination or prostate needle biopsy. The concordance between post-digital rectal examination and post-biopsy urinary samples for promoter methylation is high (82% to 94%), suggesting that urine collected after digital rectal examination may be used for genetic analysis with results similar to those in post-biopsy urine samples.

Adenomatous Polyposis Coli Protein↗

Disseminated tumor cells in breast cancer: detection, characterization and clinical relevance.

Hematogenous distant metastasis is the leading cause of cancer-related death in breast cancer and other solid tumors. By applying sensitive immunocytochemical or molecular assays, disseminated tumor cells (DTCs) in bone marrow can be detected in 20-40% of breast cancer patients without any clinical or even histopathological signs of metastasis. The detection of DTCs provides prognostic information and might help to identify patients who need adjuvant therapy, and to monitor the efficacy of adjuvant therapy. Within the last few years, various efforts have led to an increased sensitivity in the detection of DTC. This review will summarize the most important methods for DTC detection in bone marrow and for circulating tumor cells in the blood of breast cancer patients, the clinical relevance of DTCs and, finally, provide an outlook on clinical implications.

Bone Marrow Cells↗

Serum pro prostate specific antigen improves cancer detection compared to free and complexed prostate specific antigen in men with prostate specific antigen 2 to 4 ng/ml.

PURPOSE: Pro prostate specific antigen (pPSA) is a precursor form of PSA enriched in tumor compared to benign prostate tissues that may be a more specific serum marker for prostate cancer. Serum pPSA was measured in the clinically relevant early detection PSA range of 2 to 10 ng/ml. MATERIALS AND METHODS: Research use immunoassays were used to measure native and truncated forms of pPSA. The subject cohort contained 1,091 serum specimens from men enrolled in prostate cancer screening studies at 2 sites who had undergone prostate biopsy and were divided into PSA ranges of 2 to 4 ng/ml (benign 320, cancer 235) and 4 to 10 ng/ml (benign 315, cancer 221). RESULTS: In PSA ranges 2 to 4, 2 to 6, 4 to 10 and 2 to 10 ng/ml, pPSA in a ratio with free PSA (%pPSA) gave the highest cancer specificity. At 2 to 4 ng/ml and 90% sensitivity, %pPSA spared 19% of unnecessary biopsies compared to 10% for free PSA and 11% for complexed PSA(p <0.001). Similar results were obtained at PSA 2 to 6 ng/ml. At 90% sensitivity in the PSA 4 to 10 ng/ml range, %pPSA spared 31% of unnecessary biopsies compared to 20% for % free PSA and 19% for complexed PSA (p <0.0001). In the combined 2 to 10 ng/ml range, %pPSA spared 21% of unnecessary biopsies compared to 13% for % free PSA and 9% for complexed PSA (p <0.0001). CONCLUSIONS: The %pPSA significantly improved specificity for cancer detection and decreased the number of unnecessary biopsies in the PSA 2 to 4 ng/ml range. This relative improvement of %pPSA compared to % free PSA and complexed PSA was maintained throughout the PSA range of 2 to 10 ng/ml.

Biopsy, Needle↗

[Colorectal cancer: detection using the guaiac test at a primary care center].

BACKGROUND: Colorectal cancer constitutes a serious health care problem in the Western world due to its frequency and mortality. Early detection and strict follow up of disease with risk of degeneration may increase survival. The guaiac test for fecal occult blood detection (one of the first signs of cancer) may contribute to the aforementiokned. METHODS: The guaiac test was randomly offered to patients consulting in general medicine. Those who accepted were taken to group meeting in general information and the test. Patients with positive tests underwent colonoscopy. Patients delaying the conclusion of the study were remained by telephone. Participation and the lesions detected were evaluated. RESULTS: The test was offered to 1,605 subjects, of whom 1,334 attended the meetings and 1,166 completed the test. Sixty patients were found to be positive and 52 underwent colonoscopy. The most significant diagnosis were 5 carcinomas at different stages and 25 neoplastic polyps. One hundred seventy-eight people were recouperated from 481 telephoned. CONCLUSIONS: The high participation in this study concerning early detection and follow up of disease with risk of degeneration to colorectal carcinoma is emphasized, in addition to the good response to the use of the telephone. Moreover, the low rejection to colonoscopy and the important lesions detected during this study are also of note.

Adult↗

Recent advances in flow cytometric techniques for cancer detection and prognosis.

The application of flow cytometry to cancer diagnosis and the prediction of tumor behavior continues to expand. The ability of flow cytometry to examine multiple parameters of large numbers of individual cells is being exploited increasingly to characterize neoplastic processes better. This will allow closer examination of tumor heterogeneity and identification of subpopulations with different behavioral patterns. Flow cytometry is being used with greater frequency in attempts to predict tumor behavior and response to therapy. Flow cytometry may have the most to offer in this area. Diagnosis of cancer by routine histopathological examination will not be replaced by flow cytometry; flow cytometry will be used in conjunction with morphological descriptions. The detection of proliferation antigens and oncogene products, as well as cell cycling, provides information on neoplastic progression that is not readily obtainable by other methods. In addition, flow cytometry will undoubtedly be used to measure other features of neoplastic cells, such as enzyme levels and ion fluxes, which may better characterize the behavior of the tumor. Advances in flow cytometry instrumentation, light sources, fluorochrome development, and basic aspects of cellular and molecular biology will continue to permit this technology to define neoplastic cells and their behavior better, resulting in both improved patient care and a better understanding of tumor biology.

Antineoplastic Agents↗

Hepatic metastases from colorectal cancer: detection and false-positive findings with helical CT during arterial portography.

PURPOSE: To determine the sensitivity and false-positive rate of helical computed tomography during arterial portography (CTAP) in the detection of hepatic metastases from colorectal cancer. MATERIALS AND METHODS: Preoperative helical CTAP was performed to examine 23 patients (10 men and 13 women, aged 43-77 years [mean, 63 years]) who later underwent surgical tumor resection. Imaging findings were retrospectively reviewed by two radiologists and were correlated with intraoperative and histologic findings. RESULTS: Helical CTAP demonstrated 33 of 35 metastases, with diameters of 4-95 mm, that were identified in resected specimens (sensitivity, 94%). The two metastases not demonstrated were 4 and 5 mm in diameter. Five false-positive lesions were found in four patients, yielding a false-positive rate of 17% by patient analysis and 13% by lesion analysis. CONCLUSION: The sensitivity of helical CTAP in the preoperative detection of hepatic metastases is high, and its false-positive rate compares favorably with that of conventional CTAP, but future comparative studies are needed to determine which is the better modality.

Colorectal Neoplasms↗