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Strategies in lung cancer detection. Achieving early identification in patients at high risk.

Screening can be crucial for timely identification of lung cancer and thus for early treatment and a favorable prognosis. This conclusion is true particularly for persons at high risk for lung cancer, including those exposed to asbestos or silicon dust. In this article, Drs Bechtel and Petty discuss the types of screening procedures available, their cost, and the approaches and timing that are most beneficial to the public as a whole.

Humans↗

[Metastatic tumor of the heart from gall bladder cancer detected by echocardiography: a case report].

Cardiac metastases have been reported increasingly partly because of the longevity of cancer patients, but its antemortem diagnosis is frequently missed. This is due to the nonspecific clinical manifestations or relative lack of characteristic signs which are masked by the underlying disease. This is a report of a 42-year-old man diagnosed as having a metastatic cardiac tumor by echocardiography, six months after operation for squamous cell carcinoma of the gall bladder. Echocardiography revealed abnormal structures in the regions of the posterior and lateral walls of the left ventricle and interventricular septum, suggesting metastatic tumors. The cytological findings of a fine-needle aspiration biopsy specimen were squamous cell carcinoma. The patient died of cardiac failure eight months after the echocardiographic diagnosis. At autopsy, the abnormal structures in the heart were identified as cardiac metastatic tumors from gall bladder cancer. Reports of cardiac metastasis of gall bladder cancer is very rare (0-3%). The myocardial metastasis may have a more serious prognostic importance than the primary neoplasm itself; thus, its definite diagnosis is mandatory.

Adult↗

HER-2/neu gene amplification in stages I-IV breast cancer detected by fluorescent in situ hybridization.

PURPOSE: Approximately 25-30% of breast and ovarian carcinomas have amplification of the HER-2/neu oncogene. The aim of the present study was to focus on HER-2/neu gene amplification in different clinical stages of breast cancer in order to (1) determine if fluorescent in situ hybridization (FISH) can be used to detect HER-2/neu gene amplification in different clinical stages of breast cancer, (2) establish whether HER-2/neu gene amplification characterizes a subset of breast cancer in each of these stages, and (3) determine whether a trend for correlation of amplification with the clinical stage of the disease can be detected using the FISH technology. METHODS: A total of 40 specimens of formalin-fixed, paraffin-embedded breast cancer tissues were analyzed cytogenetically, in a blinded fashion, for HER-2/neu gene amplification using FISH and the Vysis LSI HER-2/neu Orange and CEP 17 Green DNA dual color probe. The criterion for "high amplification" was an amplification ratio of >4.0, that for "moderate amplification" a ratio between 2.1 and 4.0, and that for "low amplification" a ratio of 1.5-2.0. RESULTS: Using a cutoff point of > or =1.5, the overall frequency of HER-2/neu gene amplification among stage I tumors was 30% (3 out of 10). Of these, one-third (1 out of 3) showed low amplification, one-third (1 out of 3) were moderately amplified, and one-third (1 out of 3) were highly amplified. The overall frequency of HER-2/neu gene amplification among stage II tumors was 0% (0 out of 10). The overall frequency of HER-2/neu gene amplification among stage III tumors was 10% (1 out of 10). The sole tumor found positive was classified as moderately amplified by our criteria. The overall frequency of HER-2/neu gene amplification among stage IV tumors was 50% (5 out of 10). Four of the 5 tumors found positive were highly amplified. The overall frequency of gene amplification in the 40 cases studied was 22.5% (9 out of 40 tumors studied). CONCLUSION: Although a linear correlation between HER-2/neu amplification and clinical stage cannot be established at this time, it is interesting to note that when stages I and II, and when stages III and IV are combined, respectively, the latter category has a higher amplification frequency than the former. Furthermore, stage IV has the highest frequency (5 out of 10) of HER-2/neu gene amplification than all three lower stages combined (4 out of 30). This is no doubt due to the high frequency of gene amplification observed in stage IV tumors, which, interestingly, also demonstrate high level amplification of HER-2/neu gene copy numbers. Although the biologic and clinical basis for gene amplification is not clear, given the observation that the most aggressive disease stage is associated with the highest frequency of gene amplification and the most high level amplification, further exploration of HER-2/neu as a prognostic marker of poor outcome using FISH is warranted.

Breast Neoplasms↗

[Position of cervix cancer detection in Gabon over a period of 19 years].

MATERIALS AND METHODS: We report the contribution of the cytology test for screening for cervix cancer in Gabon observed in a retrospective study over 19 years (1977-1995). Data from the Libreville Faculty of Medicine cytohistopathology laboratory were used. RESULTS: Over the 19-year period, 10,838 PAP smears were performed, an average of 570,42 smears per year. Sixty-eight cases of cervix cancer were diagnosed with this test: 40 invasive carcinomas (58.83%), 5 microinvasive carcinomas (7.35%), and 23 in situ carcinomas (33.82%). During the same period, 437 cervix cancers were reported in the same laboratory without prior cytology test. CONCLUSION: In Gabon, cervix cancer is usually diagnosed at an invasive stage, hence the need for systematic detection.

Carcinoma↗

Loss of peroxisomes causes oxygen insensitivity of the histochemical assay of glucose-6-phosphate dehydrogenase activity to detect cancer cells.

Oxygen insensitivity of carcinoma cells and oxygen sensitivity of non-cancer cells in the histochemical assay of glucose-6-phosphate dehydrogenase (G6PD) enables detection of carcinoma cells in unfixed cell smears or cryostat sections of biopsies. The metabolic background of oxygen insensitivity is still not understood completely. In the present study, rat hepatocytes, rat hepatoma cells (FTO-2B), and human colon carcinoma cells (HT29) were used to elucidate these backgrounds. The residual activity in oxygen was 0%, 55%, and 80% in hepatocytes, hepatoma cells, and colon carcinoma cells, respectively. N-ethylmaleimide (NEM), a blocker of SH-groups, did not affect G6PD activity in both carcinoma cell types but reduced G6PD activity in hepatocytes by 40%. Ultrastructural localization of G6PD activity was exclusively in the cytoplasm of carcinoma cells, but in hepatocytes both in cytoplasm and peroxisomes. NEM abolished peroxisomal G6PD activity only. Histochemical assay of catalase activity demonstrated absence of peroxisomes in both carcinoma cell lines. It is concluded that absence of SH-sensitive G6PD activity in peroxisomes in cancer cells is responsible for the oxygen-insensitivity phenomenon.

Animals↗

P-glycoprotein expression in primary breast cancer detected by immunocytochemistry with two monoclonal antibodies.

We have investigated P-glycoprotein (P-gp) expression in samples of primary breast cancer from 29 patients before therapy. We employed immunohistochemical techniques using two monoclonal antibodies (C219 and MRK16) and an indirect alkaline phosphatase method. Heterogeneous expression in epithelial cells was detected with both C219 (21 of 29) and MRK16 (16 of 29). A surprising finding was P-glycoprotein expression in stromal cells with both C219 (26 of 29) and MRK16 (12 of 29). Our results suggest that significant levels of P-glycoprotein expression may be present in breast cancer before exposure to drugs associated with multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Chromosome 7 abnormalities in prostate cancer detected by dual-color fluorescence in situ hybridization.

Aneusomy of chromosome 7 and loss at 7q (especially 7q31.1) have been reported in prostate cancer. To further investigate abnormalities of 7q and the relationship with whole chromosome 7 changes, we have conducted a dual-color fluorescence in situ hybridization (FISH) analysis on isolated nuclei from 28 primary prostate cancers. A pericentromeric probe for chromosome 7, five newly isolated sequence-specific bacterial artificial chromosome (BAC) probes from 7q31.1, and one BAC for the epidermal growth factor receptor (EGFR) gene at 7p12 were used in dual color hybridizations. Pericentromeric probes for chromosomes X and 4 were also used as controls. Sixteen (57.1%) of the 28 tumors showed clonal aberrations. Nine of them were trisomy 7 and four were hypertetrasomy for chromosome 7. Deletions at 7q31.1 were found in two of the high grade tumors. With the exception of these two cases, all other cases showed concordant results using all probes. These findings confirm previous studies that aneusomy of 7 is associated with prostate cancer progression, and there may be a tumor suppressor gene (TSG) at 7q31.1 which is associated with tumor progression. In addition, our study indicates: (1) the deletion pattern of individual nuclei infers that deletions at 7q31.1 precede reduplications of chromosome 7; and (2) the amplification of EGFR was not detected at the DNA level, suggesting that activation of this oncogene may play a minor role in prostate cancer.

Aneuploidy↗

Early breast cancer: detection of recurrence after conservative surgery and radiation therapy.

To determine the clinical and mammographic features of recurrent breast cancer after tumorectomy and radiation therapy, the authors reviewed the clinical history and serial mammograms of 48 patients with suspected recurrence. Of patients with recurrent disease, seven had positive mammograms alone, nine had positive findings at physical examination alone, and eight had both positive mammograms and positive results of physical examination. Positive mammographic findings included the development of new fine calcifications (six patients), a new mass (five patients), mass and calcifications (one patient), increasing opacity (two patients), or skin thickening (one patient). Patients in whom the breast recurrence was detected mammographically alone were less likely to develop metastatic disease in subsequent follow-up than when results of physical examination were positive at the time of breast recurrence. Serial mammographic and clinical examinations are complementary for optimal detection of recurrence after conservative surgery and radiation therapy.

Breast Neoplasms↗

The Potential of F-18-FDG PET in Breast Cancer. Detection of Primary Lesions, Axillary Lymph Node Metastases, or Distant Metastases.

This retrospective study was done to evaluate the utility of 2-[F-18]fluoro-2-deoxy-D-glucose positron emission tomography (F-18-FDG PET) in identifying primary and recurrent breast cancer and lymph node metastases. One hundred whole-body PET scans of 87 patients were reviewed. PET results obtained with F-18-FDG and an ECAT/EXACT-921 or an ECAT-931 (Siemens/CTI) were based on visual interpretation, or standardized uptake values (SUVs), related to histology and also compared to computerized tomography (CT) and mammography results. The sensitivity for PET in detecting primary (N = 35 studies) and recurrent breast cancer (N = 65 studies) was 96% and 85% with a specificity of 91% and 73%. The sensitivity for lymph node metastases at the time of initial diagnosis was 100% with a specificity of 100%. Quantitative SUV information did not improve the accuracy of F-18-FDG PET in identifying primary breast cancers. The results suggest that whole-body PET is useful in detecting recurrence or metastases, may be useful in detecting lymph node metastases prior to initial axillary lymph node dissection, but is less sensitive in excluding axillary lymph nodes metastases later in the course of the disease.

Journal Article↗

Meta-analysis and pooled re-analysis of copy number changes in colorectal cancer detected by comparative genomic hybridization.

BACKGROUND: Comparative genomic hybridization (CGH) provides an insight into chromosomal changes associated with colorectal cancer (CRC) development. However, a problem with many studies is the limited cohort size, making the significance of some findings unclear. MATERIALS AND METHODS: To derive a better insight into the chromosomal changes associated with CRC, we performed a meta-analysis and pooled re-analysis of published metaphase CGH data. RESULTS: In addition to recurrent alterations, gains of 20 13q, 8q and 7p and loss of 18, 17p, 8p and 4p, pooling identified less frequent, but significant changes, including gain of 1q and 3, and losses from 6q, 9p and 21q. CONCLUSION: These additional alterations may be characteristic of some tumors and thus have relevance to CRC biology. Meta-analysis not only has the potential to detect novel changes, present at low frequency in several independent studies, but can provide greater reliability for their detection than single studies alone.

Adenoma↗

[Breast cancer detected by a stellar opacity. Histologic characteristics: 155 cases].

UNLABELLED: Retrospective study (1985-1998) concerning surgical and histopathological features of 155 subclinical breast cancers revealed by spiculated opacity on screening mammograms. MATERIALS AND METHODS: The patients were 44-78 years old (mean age, 58.5 years), 129 were postmenopausal. Preoperative localization was stereotactic in 57 instances (36.5%), sonographic in 98 instances (63.5%). Maximum tumor diameter varied from four to 25 millimeters (mean diameter 11 mm), below 10 min in 97 cases, below 5 mm in 15 cases. Axillary lymph node dissection was performed immediately (95%) or secondarily (5%). RESULTS: Subclinical breast tumors exhibiting spiculated picture were infiltrating carcinomas: Infiltrating ductal carcinoma (IDC) in 130 cases (84%), infiltrating lobular carcinoma (ILC) in 25 cases (16%). Not any ductal carcinoma in situ (DCIS) was detected by such an irregular opacity. The grading according to Scarff-Bloom-Richardson was used in IDC: 95 grade I (73%), 31 grade II (24%), four grade III (3%). Hormone receptor status was obtained upon 145 tumors: both estrogen receptors were present in 125 cases (86%). Axillary lymph node involvement (N+) was found in ten cases (6%), always concerning IDC > 5 mm. Conservative surgery was achieved in mort cases (97%). DISCUSSION: Subclinical breast cancers revealed by spiculated opacity were predominantly corresponding to infiltrating process IDC or ILC, in contrast with breast cancers revealed by microcalcifications, mainly meaning DCIS. In our experience mammographically-detected spiculated malignant tumors were not bearing unfavourable pathological or biological features: they appeared commonly well differentiated and hormonosensitive, furthermore axillary lymph nodes were rarely involved.

Adult↗

[Occult breast cancer. Detection and radioguided surgery with 99mTc-MIBI].

We include those patients who present with an isolated metastasis of axillary adenopathy in the occult primary breast cancer group. Presumably, the primary tumor is a primitive breast carcinoma, unsuspected until this moment and not clinically demonstrable by mammography or ultrasonography. When no method succeeds in confirming the primary breast lesion, the patients are usually treated assuming the existing of breast cancer. Several diagnostic methods have been used to find the primary breast lesion. Magnetic Resonance imaging (MRI), Positron Emission (PET) and Doppler sonography have been used in this way and several papers present the results reached with them. Our group incorporates detection and radioguided surgery with 99mTechnetium (99mTc) methoxyisobutil isonitrile into the study of these patients. We perform a planar scintimammography and SPECT (Single Photon Emission Computed Tomography) with 99mTc-MIBI. If the radioisotopic method shows a functional image compatible with a carcinoma, a gamma detecting probe is then used to locate the lesion and guide its surgical removal. In this paper, we present the application of the technique in 5 cases and describe the technique and its possibilities. Its advantages are explained in comparison with other methods. The dosimetric values found in the performance of the technique are reported. We consider that detection and radioguided surgery with 99mTc-MIBI in the diagnosis and treatment of occult breast cancer adds an effective tool and means progress in the approach to this disease.

Adenocarcinoma↗

Active surveillance for prostate cancers detected in three subsequent rounds of a screening trial: characteristics, PSA doubling times, and outcome.

OBJECTIVES: To study active surveillance as a management option for the important number of prostate cancer patients who would not have been diagnosed in the absence of screening. PATIENTS AND METHODS: We analyzed baseline characteristics and outcome parameters of all men on active surveillance who were screen-detected in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). Recruitment and surveillance of men were not guided by a protocol but depended on individual decisions of patients and their physicians. RESULTS: Active surveillance was applied in 278 men detected by screening from 1993 to 2006. At diagnosis, their median age was 69.8 yr (25-75p; 66.1-72.8); median PSA 3.6 ng/ml (25-75p; 3.1-4.8), and the clinical stage was T1c in 220 (79.1%) and T2 in 58 (20.9%). During the follow-up of median 3.4 yr, 103 men (44.2%) had a PSA doubling time that was negative (ie, half-life) or longer than 10 yr. Men detected at rescreening were significantly more likely to be on active surveillance, and they had more beneficial characteristics. Deferred treatment was elected in 82 cases (29.0%). Overall survival was 89% after 8 yr; the cause-specific survival was 100%. CONCLUSIONS: This report shows a beneficial, although preliminary, outcome of screen-detected men managed on active surveillance. Men were more likely to be on active surveillance if the disease was detected at repeated screening. The report also shows that an important proportion of men have prolonged PSA doubling times, although the value of this parameter has not been established in untreated men.

Adult↗

Identification of oncofetal fibronectin in patients with advanced epithelial ovarian cancer: detection in ascitic fluid and localization to primary sites and metastatic implants.

BACKGROUND: The mechanisms by which metastatic ovarian cancer adheres to peritoneal surfaces are not well understood. A role for tumor-derived extracellular matrix adhesive molecules such as fibronectin (FN) has been proposed. Because oncofetal fibronectin (onfFN) isoforms function in the adhesion of trophoblasts and have been identified in association with several malignancies, we sought to study onfFN in patients with advanced epithelial ovarian cancer. METHODS: Total FN was identified with the nonspecific anti-FN monoclonal antibody CAF. OnfFN was identified using the specific monoclonal antibodies FDC-6 and X18A4. These antibodies were applied to: 1) ascitic fluid from advanced epithelial ovarian cancer patients and peritoneal fluid from patients without pathologic conditions and 2) tissue sections of primary lesions and metastatic ovarian cancer implants. Comparative histologic specimens included normal ovarian tissue and small bowel implants of endometriosis. RESULTS: When measured by sandwich enzyme-linked immunoadsorbent assay, all peritoneal fluids (32 malignant and 32 benign) contained marked quantities of total (CAF reactive) FN, although malignant ascites had higher concentrations than benign samples (173.2 +/- 36.8 microg/mL vs. 76.4 +/- 31.8 microg/mL; P = 0.001). Malignant ascites also had significantly higher levels of onfFN than benign peritoneal fluid (FDC-6: 3.4 +/- 0.6 vs. 0.9 +/- 0.2 microg/mL; and X18A4: 5.1 +/- 1.3 vs. 1.1 +/- 0.4 microg/mL; P = 0.0001). Immunohistochemical staining of malignant lesions revealed prominent localization of both CAF reactive FN and onfFN to the stroma surrounding epithelial tumor nests. More delicate fibrillar staining within tumor nests also was evident. In contrast, implants of endometriosis revealed strong stromal staining for CAF reactive FN but not for onfFN. CONCLUSIONS: These results demonstrate the presence of onfFN in advanced ovarian malignancies. We speculate that onfFN may participate in tumor-associated peritoneal adhesive interactions.

Adenocarcinoma, Clear Cell↗

Report of colon cancer detection in mass surveys using immunological occult blood test (Latex method).

Occult blood test for the screening of colon cancer has been made by immunological method using latex agglutination for 4 years since 1988. A total of 35,139 persons have received the screening test and out of 1886 persons, that is, 5.4% showed positive. Five hundred seventy of the positive result subjects (30.2%) underwent barium enema examination. Three hundred fifty nine subjects (62.8%) showed some abnormal findings. They underwent colonoscopic examination and 45 of them (7.9%) had colon cancer. Twenty six of these were of early stage type and 19 persons were of advanced stage.

Adenocarcinoma↗