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PubMed1986

Diagnostic techniques in prostatic cancer.

At present no single test is effective in detecting prostatic carcinoma, although some newer tests show promise. Several investigators are working to increase the specificity and sensitivity of various radioimmunoassays for prostatic cancer detection, but to date this research has not been rewarding. Careful rectal examination and close attention to the patient's symptoms may still be the only keys to diagnosis. Patients in their 50s and 60s with acute onset of symptoms have a relatively high incidence of prostatic carcinoma. These patients should have a rectal examination and aspiration biopsy cytology of any suspicious areas found on examination. Possibly these patients should have aspiration biopsy cytology even in the absence of suspicious findings to screen for disease before it becomes an obvious clinical entity. This is perhaps the best approach to prostatic cancer, ie, attack at a time in which there are fewer cells and a greater chance of cure.

Acid Phosphatase↗
PubMed2004

Molecular basis and diagnostics of hereditary colorectal cancers.

Hereditary colorectal cancer syndromes are classified according to the presence of unusually large number of adenomatous or hamartomatous polyps, or their absence. The latter category includes hereditary non-polyposis colorectal cancer (Lynch syndrome) and its variants Muir-Torre and Turcot's syndromes. Adenomatous polyposis syndromes include familial adenomatous polyposis (FAP) and its variants, and the recently identified MYH- (mutY homolog)-associated polyposis. Hamartomatous polyposis syndromes include juvenile polyposis, Peutz-Jeghers syndrome, and Cowden syndrome, which is now included within the broader category 'PTEN (phosphatase and tensin homolog) hamartoma tumour syndrome'. Other syndromes such as the 'hereditary breast and colon cancer' and 'familial colorectal cancer' are not yet fully characterized. This review addresses the molecular basis of these syndromes with particular reference to the recent advances in this rapidly progressive field and the applications of such knowledge in diagnosis and management.

Adenomatous Polyposis Coli↗
PubMed1980

The comparative diagnostic accuracy of cancer-cell detection obtained with Ficoll-Hypaque gradient separation and standard centrifugation technics on body-cavity fluids.

Ninety-two consecutive samples of body-cavity fluids from patients with confirmed or suspected cancer were compared for accuracy of diagnosis using a Ficoll gradient test and a standard centrifugation test. The percentage of positive test results was 76% (70/92) with the Ficoll test and 64% (59/92) with the routine test. The Ficoll and routine tests also gave a significant difference in the classification of malignancy, with the latter test giving a significantly higher proportion of negative or inconclusive test results. Besides the improved test results, the Ficoll gradient test has the further advantages of being less expensive and requiring only standard laboratory equipment. Elimination of blood and cellular debris by the procedure results in quick and easy cytologic screening. The Ficoll test is strongly recommended for those clinical fluids suspected to be positive for malignancy, especially where the routine test is negative or inconclusive.

Body Fluids↗
PubMed2004

Statistical methods of translating microarray data into clinically relevant diagnostic information in colorectal cancer.

MOTIVATION: It is a common practice in cancer microarray experiments that a normal tissue is collected from the same individual from whom the tumor tissue was taken. The indirect design is usually adopted for the experiment that uses a common reference RNA hybridized both to normal and tumor tissues. However, it is often the case that the test material is not large enough for the experimenter to extract enough RNA to conduct the microarray experiment. Hence, collecting n cases does not necessarily end up with a matched pair sample of size n. Instead we usually have a matched pair sample of size n1, and two independent samples of sizes n2 and n3, respectively, for 'reference versus normal tissue only' and 'reference versus tumor tissue only' hybridizations (n=n1 + n2 + n3). Standard statistical methods need to be modified and new statistical procedures are developed for analyzing this mixed dataset. RESULTS: We propose a new test statistic, t3, as a means of combining all the information in the mixed dataset for detecting differentially expressed (DE) genes between normal and tumor tissues. We employed the extended receiver operating characteristic approach to the mixed dataset. We devised a measure of disagreement between a RT-PCR experiment and a microarray experiment. Hotelling's T2 statistic is employed to detect a set of DE genes and its prediction rate is compared with the prediction rate of a univariate procedure. We observe that Hotelling's T2 statistic detects DE genes more efficiently than a univariate procedure and that further research is warranted on the formal test procedure using Hotelling's T2 statistic. CONTACT: bskim@yonsei.ac.kr.

Adult↗
PubMed2005

Utility of alpha-methylacyl coenzyme A racemase (p504s antibody) as a diagnostic immunohistochemical marker for cancer.

Alpha-methylacyl-coenzyme A racemase (AMACR; P504S) is a mitochondrial and peroxisomal enzyme involved in the metabolism of branched-chain fatty acid and bile acid intermediates. Recently, AMACR has been demonstrated to be overexpressed in localized and metastatic prostate cancer and in high-grade prostatic intraepithelial neoplasia but not in normal prostatic glands, suggesting that it may be an important tumor marker. This study examines AMACR expression in a variety of human cancers to assess its viability as a tumor marker in the clinical setting. Two hundred sixty-three cancers from different sites were examined in three multitumor tissue micro arrays, which included two or three tissue cores (1.0 mm in diameter) from each neoplastic and normal tissue specimen. Cancers studied included breast (94 cases), prostate (38), lung (28), endometrium (27), colon (29), ovary (26), and melanoma (21). Normal tissues in the microarray were prostate (15), lung (6), endometrium (5), colon (4), ovary (2), and skin (3). Sections were immunostained, after prior pressure cooker antigen retrieval, using rabbit monoclonal AMACR antibody (1:40) (Zeta Corp, Sierra Madre, CA) and horseradish peroxidase-labeled polymer conjugated secondary antibody (Envision, Dako, Carpinteria, CA). A section of prostate cancer and prostatic intraepithelial neoplasia was used as positive control. Protein expression was scored as negative, weak (faint cytoplasmic or granular apical staining), moderate (diffuse granular cytoplasmic stain), and strong (diffuse intense cytoplasmic stain). Only moderate and strong staining was considered as positive staining, based on prior work. AMACR protein overexpression was found in several cancers, including prostate (34/38 [89.5%]), colon (13/29 [44.8%]), lung (4/28 [14.3%]), melanoma (2/21 [9.5%]), endometrium (2/27 [7.4%]), and breast (3/94 [3.2%]). None of the ovarian cancers (26 cases) demonstrated AMACR overexpression. AMACR expression was not present in any of the normal tissues nor in benign prostatic tissue associated with prostate carcinomas. This study suggests that AMACR is potentially an important tumor marker, particularly for prostate and colon cancer. It may be a useful adjunct to an immunohistochemical panel employed in the differential diagnosis of colon versus ovarian and breast carcinoma; the latter two infrequently express AMACR.

Biomarkers, Tumor↗
PubMed2004

A diagnostic test for prostate cancer from gene expression profiling data.

PURPOSE: Multiple recent studies show excellent classification accuracy using bioinformatics tools applied to expression profiling data on various tumors. However, the clinical applicability of these techniques remains unfulfilled because of difficulty in translating complex multigene mathematical algorithms into reproducible, platform independent tests. We recently developed a broadly applicable platform independent method based on simple ratios of gene expression to diagnose and predict outcome in cancer. In the current study we applied this technique to the diagnosis of prostate cancer. MATERIALS AND METHODS: We developed a ratio based predictive model using a training set of 32 samples with previously published gene profiling data. We then tested and refined the model using additional independent samples with previously published microarray data from another source (that is the test set of 34 samples). Finally, the optimal ratio based test was examined with quantitative reverse transcriptase-polymerase chain reaction for data acquisition in a third cohort of samples consisting of 10 frozen normal and 10 tumor prostate tissues. RESULTS: A 3-ratio test using 4 genes was 90% accurate (18 of 20 samples) for distinguishing normal prostate and prostate cancer samples obtained at surgery (Fisher's exact test p = 0.0007). This test did not result in any false-negative findings. CONCLUSIONS: We describe and validate a new gene ratio based test for the diagnosis of prostate cancer, which was developed from the analysis of extensive gene profiling data for the diagnosis of prostate cancer. This test can be easily adapted to the clinical arena without the need for complex computer software or hardware. We anticipate that the gene ratio based diagnosis of prostate cancer using fine needle aspirations could serve as a useful adjunct to standard histopathological techniques.

Gene Expression Profiling↗
PubMed2005

Anastomotic leak following mesorectal excision for rectal cancer: true incidence and diagnostic challenges.

OBJECTIVE: Anastomotic leakage is a potentially serious complication of low anterior resection which may be accompanied by clinical symptoms (clinical leak) or may be silent (subclinical leak). In this study the true incidence of the complication was evaluated, and the diagnostic accuracy of clinical symptoms, conventional rectal radiography (CRR) and computed tomography (CT) was compared. PATIENTS AND METHODS: Fifty-six consecutive patients were included in a prospective trial. Clinical parameters were recorded and CRR and CT performed 6-10 days postoperatively or earlier if a leak was suspected. Endoscopy was performed three months postoperatively. RESULTS: Based on all available information including late endoscopy, 5 (9%) patients had clinical leak and five a leak that was asymptomatic during the hospital stay. Clinical assessment, CRR and CT during the hospital stay had an accuracy of 82%, 93% and 94%, respectively, and a sensitivity of 50%, 60% and 57%, respectively. The specificity of clinical assessment was 89%, whereas both CRR and CT had a specificity of 100%. CONCLUSION: The incidence of anastomotic leakage seemed acceptable when compared with other series. Fifty per cent of the leaks were silent. CRR and CT may be false negative and immediate treatment should be started if clinical signs are highly suggestive of leak, irrespective of radiological findings CT was not more accurate than CRR in detecting anastomotic leak.

Anastomosis, Surgical↗