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PubMed2006

Mitochondrial DNA as a potential tool for early cancer detection.

The recent surge in mitochondrial research has been driven by the identification of mitochondria-associated diseases and the role of mitochondria in apoptosis. Both of these aspects have identified mitochondrial analysis as a vital component of medical research. Moreover, mitochondria have been implicated in the process of carcinogenesis because of their vital role in energy production, nuclear-cytoplasmic signal integration and control of metabolic pathways. Interestingly, at some point during neoplastic transformation, there is an increase in reactive oxygen species, which damage the mitochondrial genome. This accelerates the somatic mutation rate of mitochondrial DNA. It has been proposed that these mutations may serve as an early indication of potential cancer development and may represent a means for tracking tumour progression. The purpose of this review is to explore the potential utility that these mutations may afford for the identification and monitoring of neoplasia and malignant transformation where appropriate body fluids or non-invasive tissue access is available for mitochondrial DNA recovery. Specifically, prostate, breast, colorectal, skin and lung cancers are discussed.

DNA, Mitochondrial↗
PubMed1997

Frequent homozygous deletion of cyclin-dependent kinase inhibitor 2 (MTS1, p16) in superficial bladder cancer detected by fluorescence in situ hybridization.

Deletion of all or part of chromosome 9 is a well-described genetic alteration in bladder tumors. It has been proposed that inactivation of a tumor-suppressor gene on chromosome 9 is an important event in tumor development. Recent reports have supported cyclin-dependent kinase inhibitor 2 (CDKN2, also known as MTS1, INK4, p16) at 9p21 as a candidate tumor-suppressor gene in solid tumors. However, the prevalence of CDKN2 mutations in primary bladder tumors has been controversial. Therefore, we applied gene-specific probes for CDKN2 and the interferon alpha gene (IFNA), also located at 9p21, to characterize further the genomic deletions at this locus in bladder cancer. Seventeen superficial (pTa or pT1) bladder tumor specimens were examined for gene deletion by fluorescence in situ hybridization. Dual-labeling hybridization with a repetitive pericentromeric probe for chromosome 9 and a gene-specific probe for CDKN2 was performed to characterize the gene copy number in relation to the chromosome 9 copy number on a cell-by-cell basis. Homozygous deletion for CDKN2 without homozygous IFNA deletion was found in 5 of 17 tumors tested. Both genes were deleted in one additional case, and one tumor showed deletion of IFNA without deletion of CDKN2. Homozygous deletion at the 9p21 locus was found only in tumors having monosomy for the chromosome 9 centromeric signal. These results indicate that the homozygous deletion of the CDKN2 gene is a frequent and early event in superficial bladder cancer.

Adult↗
PubMed2005

A multi-resolution approach for content-based image retrieval on the Grid--application to breast cancer detection.

OBJECTIVES: Hospitals and medical centers are producing more and more data that need to be processed. Those data are confidential, heterogeneous, and limited to the geographic site where they have been produced. Unless properly anonymized, they cannot be distributed on wide area networks. METHODS: Grid technologies allow the globalization of storage and processing resources, and enable large-scale experimentations on distributed data. They constitute a promising tool to treat the different data and analyze the knowledge they contain, while offering secured access and high-performance computing capacities to the different users. Our aim is to evaluate the possibilities of grid technologies for handling medical data. RESULTS AND CONCLUSIONS: In this paper, we focus on a breast cancer diagnosis assistance tool, based on distributed and incremental knowledge construction and a content-based image retrieval system. We analyze the different scenarios of uses of such a tool. We further propose an algorithm that indexes mammographic images for content-based query purposes. This algorithm is tested on images of different resolutions in order to reduce the indexation time and we analyze its performance with experiments on the grid.

Algorithms↗
PubMed1993

The role of ultrasound in prostate cancer detection in patients with an elevated prostate specific antigen level but no prostatic nodule.

An increased level of prostate specific antigen (PSA) in the blood is a relatively sensitive indicator of prostate disease; a significant minority of men with increased PSA will have prostate carcinoma. A total of 736 men with a PSA elevation of greater than 4.2 without a rectally palpable prostate mass were evaluated with transrectal ultrasound at the Ultrasound Institute of Baltimore over a three-year period. Transrectal biopsy under ultrasound control was performed when a localized mass was seen on ultrasound or the prostate was small and the PSA level significantly elevated (93% of the series underwent biopsy). There was a positive biopsy yield for cancer of 38.5% in the cases biopsied. This high positive yield was achieved by combining high quality ultrasound with two to three samples from a visible mass and random samples from other sites.

Adult↗
PubMed2000

Genetic imbalances in precursor lesions of endometrial cancer detected by comparative genomic hybridization.

Endometrial hyperplasia is regarded as a precursor lesion of endometrioid adenocarcinomas of the endometrium. The genetic events involved in the multistep process from normal endometrial glandular tissue to invasive endometrial carcinomas are primarily unknown. We chose endometrial hyperplasia as a model for identifying chromosomal aberrations occurring during carcinogenesis. Comparative genomic hybridization (CGH) was performed on 47 formalin-fixed, paraffin-embedded specimens of endometrial hyperplasia using the microdissection technique to increase the number of tumor cells in the samples and reduce contamination from normal cells. CGH analysis revealed that 24 out of 47 (51%) samples had detectable chromosomal imbalances, whereas 23 (49%) were in a genetically balanced state. The incidence of aberrant CGH profiles tended to parallel dysplasia grade, ranging from 22% aberrant profiles in simple hyperplasia to 67% in complex hyperplasia with atypia. The most frequent imbalances were 1p, 16p, and 20q underrepresentations and 4q overrepresentations. Copy number changes in 1p were more frequent in atypical complex hyperplasia than in complex lesions without atypical cells or simple lesions (42% versus 20% and 0%). Our results show that endometrial hyperplasia reveals recurrent chromosomal imbalances which tend to increase with the presence of atypical cells. The most frequent aberrations in endometrial cancer, 1q and 8q overrepresentations, are not present or are rare in its precursor lesions. This analysis provides evidence that tumorigenesis proceeds through the accumulation of a series of genetic alterations and suggests a stepwise mode of tumorigenesis.

Adenocarcinoma↗
PubMed2000

Performance of a neural network in detecting prostate cancer in the prostate-specific antigen reflex range of 2.5 to 4.0 ng/mL.

OBJECTIVES: To explore the potential role of a neural network-derived algorithm in enhancing the specificity of prostate cancer detection compared with the determination of prostate-specific antigen (PSA) and free PSA (fPSA) while maintaining a 90% detection rate. Recent information suggests that the incidence of detectable prostate cancer is similar in men whose PSA values range from 2.5 to 4.0 ng/mL and from 4.0 to 10.0 ng/mL. If the PSA threshold triggering a prostate biopsy is lowered to 2.5 ng/mL, approximately 13% of men older than 50 would be added to the patient biopsy pool. METHODS: One hundred fifty-one men were enrolled in a prospective, Institutional Review Board-approved protocol to evaluate the incidence of cancer in a population of men who participated in an early-detection program and whose PSA level was between 2.5 and 4.0 ng/mL. All the men underwent biopsy using an 11-core multisite-directed biopsy scheme, and all biopsy specimens were examined by one pathologist. All men had a second blood specimen drawn before the biopsy for a determination of serum PSA, creatinine kinase, prostatic acid phosphatase, and fPSA. A new neural network algorithm was developed with PSA, creatinine kinase, prostatic acid phosphatase, fPSA, and age as input variables to produce a single-valued prostate cancer detection index (PCD-I). This new algorithm was then prospectively tested in the 151 men. Performance parameters (including sensitivity, specificity, positive and negative predictive values, and biopsies saved) were calculated, and a comparative analysis was performed to evaluate the differences among the new algorithm, percent fPSA, PSA density, and PSA density-transition zone. RESULTS: Cancer was histologically confirmed in 24.5% (37 of 151) of the men. The median age of the men was 62 years (range 43 to 74). At a sensitivity of 92%, the specificity for percent fPSA was 11%. The new algorithm (PCD-I) demonstrated an additional enhancement of specificity to 62% at 92% sensitivity. Clinically, the PCD-I would result in a savings of 49% (74 of 151) of all biopsies or 63.6% (71 of 114) of all unnecessary biopsies. CONCLUSIONS: A new generation algorithm, derived from a neural network (PCD-I) incorporating the parameters of age, creatinine kinase, PSA, prostatic acid phosphatase, and fPSA can significantly enhance the specificity and reduce the number of biopsies while maintaining a 92% sensitivity rate.

Acid Phosphatase↗
PubMed1995

[Analysis of numerical chromosomal aberrations in bladder cancer detected by fluorescence in situ hybridization].

The recently introduced fluorescence in situ hybridization method (FISH method) is a chromosomal analysis for examining interphase nuclei and seems to be a promising approach for chromosomal analysis of a solid tumor, which is considered hard to deal with by a conventional chromosomal staining method. In the present study, a bladder tumor (transitional cell carcinoma) was evaluated by chromosomal analysis, including interphase nuclei, with this FISH method to examine chromosomal numerical aberration in relation to the grade and stage, expecting successful, accurate determination of reliable prognostic factors based on its relapse and invasive intensity. Tissue specimens obtained from 20 patients with bladder tumor (transitional cell carcinoma) were used. The probe used in this study was specific for chromosome No. 1, 7, and 9, which were frequently indicated as being abnormal by a conventional chromosomal staining method. As a result, a tendency towards polysomy was observed in chromosome No. 1 and 7 of high grade invasive cancer cases, while a tendency towards monosomy was evident in chromosome No. 9 of low grade noninvasive cancer cases. From the results mentioned above and consideration of related literatures, it was suggested that monosomy of chromosome No. 9 is important as an index for knowing changes in the initial developmental stage of bladder tumor and polysomy of chromosome No. 1 and 7 is important as an index for knowing changes in the progressive stage.

Adult↗
PubMed1982

Experimental study for cancer diagnosis with positron-labeled fluorinated glucose analogs: [18F]-2-fluoro-2-deoxy-D-mannose: a new tracer for cancer detection.

18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and 18F-2-fluoro-2-deoxy-D-mannose (18F-FDM) were tested as tumor diagnostic agents in a transplantable rat tumor and rabbit tumors. Tissue distribution studies in rats showed high tumor uptakes of both radiopharmaceuticals. The tumor uptake reached 2.65 +/- 0.61% dose 18 dose F-FDG/g and 2.65 +/- 0.81% dose 18F-FDM/g at 60 min and remained relatively constant until 120 min. Blood clearance both 18F-FDG and 18F-FDM was very rapid and tumor-to-blood ratios reached 22.1 and 29.4 at 60 min, respectively. Tumor-to-tissue ratios of both radiopharmaceuticals were very high in most organs, especially in the liver, kidney, and pancreas. Positron emission tomography (PET) of rabbit tumor with 18F-FDM clearly delineated the main tumor, central necrosis, and lymph node metastases. These data suggested that 18F-FDM, which is a by-product of 18F-FDG synthesis was also an excellent cancer diagnostic agent as well as 18F-FDG. This is not only a new feature of 18F-FDM, but also an economical improvement on cancer diagnosis by PET.

Animals↗
PubMed1988

Breast cancer detection: age-related significance of findings on physical exam and mammography.

Data of 909 consecutive patients who underwent physical exam (PE), mammography (MG), and breast biopsy were analyzed in a retrospective study. Preoperative findings of PE and MG were classified as (1) suspicious for malignancy, (2) probably benign lesion, (3) normal and correlated with histology of the biopsy and the patient's age. Sensitivity of PE remained on a 0.9 level approximately up to age 50 and dropped to 0.78 and 0.85 respectively thereafter. Sensitivity of MG was slightly lower and was 0 in the age group 30 years and younger. Specificity of PE rose from 0.52 to 0.84 and dropped to 0.55 in women above 70 years. Specificity of MG decreased from 0.9 to 0.4 over the age groups. The relatively low positive predictive value of both PE and MG--particularly in the lower age groups--leads to an excessive rate of benign biopsies up to the age of 60. Due to suboptimal sensitivity PE and MG have to be used as a combined diagnostic modality if a reduction of breast cancer mortality is to be accomplished. Screening programs are of particular efficacy in women over 45 years of age due to age-dependent incidence figures and diagnostic sensitivity of PE and MG in this age group.

Adolescent↗
PubMed2001

The value of a single biopsy with 12 transperineal cores for detecting prostate cancer in patients with elevated prostate specific antigen.

PURPOSE: Prostate cancer detection on standard sextant biopsy is considered inadequate. Various biopsy protocols have been introduced to improve cancer diagnosis. We report our experience with transperineal 12-core prostate biopsy. MATERIALS AND METHODS: In a prospective study 650 patients underwent prostate specific antigen (PSA) measurement during a 15-month period, of whom 141 with PSA greater than 4 ng./ml. also underwent transperineal 12-core prostate biopsy using the fan technique. Median PSA was 8 ng./ml. (range 4.1 to 5,000). RESULTS: Prostate cancer was detected in 72 of the 141 patients (51%), including 44 of the 97 (45%) with PSA between 4.1 and 10 ng./ml. This incidence is higher than previously reported in the literature using other biopsy techniques. Disease was low grade Gleason 2 to 4 in 4 cases (5%), intermediate grade Gleason 5 to 6 in 26 (35%) and high grade Gleason 7 to 10 in the remaining 42 (60%). CONCLUSIONS: A high cancer detection rate is achieved by 12-core transperineal prostate biopsy. Most tumors represent clinically significant cancer. Further randomized trials are required to confirm these data.

Aged↗
PubMedDate not supplied

Genetic discordance between primary tumours and metastases of head and neck cancer detected by microsatellite analysis.

Very little is known about possible intra-tumoural genetic heterogeneity between primary tumours and lymph node metastases in head and neck squamous cell carcinoma (HNSCC). To investigate this phenomenon, we analysed 96 micro-dissected tumour samples for allelic imbalance at four of the most frequently altered chromosomal locations in HNSCC (3p14.2; 9p21; 11q23.3; 17p13.1) using microsatellite markers. From 23 patients, matched pairs of primary tumour and lymph node metastasis were analysed. Discordance in the allelic distribution was identified in 8 cases (35%). With one exception, the metastasis contained a more balanced allelic status than the primary tumour. In contrast, in a group of 25 tumours with two anatomically different samples from the primary tumour site, discordance was identified in only 3 tumours (13%). These results are compatible with the dissemination of subclones from the primary tumour site with a more balanced allelotype in the metastasis. In our opinion, several scenarios could explain this phenomenon. From a clinical point of view, genetic discordance between the metastasis and the primary tumour must be taken into consideration when establishing molecular biologic markers for choice of therapy and prognosis in head and neck cancer.

Allelic Imbalance↗
PubMedDate not supplied

Improvement of liver cancer detection with simultaneous assessment of circulating levels of free alpha-fetoprotein (AFP) and AFP-IgM complexes.

We assessed the presence of alpha-fetoprotein (AFP) complexed with IgM (AFP-IgM IC) in serum of patients affected by hepatocellular carcinoma (HCC), cirrhosis and chronic hepatitis as well as in healthy subjects by means of a dedicated ELISA assay. The amount of AFP-IgM IC was expressed in arbitrary units (AU) on a reference standard curve. Free AFP (FAFP) levels were determined in parallel in each sample by means of an automated immunoassay system. The mean serum concentration of AFP-IgM IC was significantly higher in HCC patients (mean +/- SD: 1378.3 +/- 2935.7 AU/mL) than in cirrhotic patients (129.8 +/- 261.4 AU/mL) and in patients with chronic hepatitis (80.9 +/- 168.9 AU/mL) (p < 0.01). HCC patients had FAFP values above the 20 ng/mL cutoff in 44% of cases (22/50) and AFP-IgM IC values above the 120 AU/mL cutoff in 60% of cases (30/50). The occurrence of the free and IgM-complexed form of circulating AFP did not overlap, and 82% of patients (41/50) were positive for at least one marker. The results indicate that AFP-IgM IC is a complementary serological marker to FAFP and that the combination of these biomarkers may be useful in the diagnosis of liver cancer.

Adult↗
PubMed2004

Breast screening outcomes in women with and without a family history of breast and/or ovarian cancer.

OBJECTIVES: To compare breast screening outcomes between women with a moderate or strong family history of breast and/or ovarian cancer with those without such a history. SETTING: The Ontario Breast Screening Programme (OBSP) is a population-based programme offering mammography and clinical breast examination to Ontario women of 50 and older. METHODS: Data from a cohort of 143,574 women screened by the OBSP from 1996 to 1997 were included. Referral rates, cancer detection rates, positive predictive values and the histological features of screen-detected cancers were examined within family history groups, age groups and screening modalities. Logistic regression analysis of cancer detection was conducted to adjust for potential confounding variables; subgroup analysis by hormone replacement therapy (HRT) use was also undertaken. RESULTS: Compared with women with no family history, women with a moderate or strong family history of breast and/or ovarian cancer were more likely to have their cancer detected (odds ratio [OR]=1.44, 95% confidence interval [CI] 1.20-1.74 and OR=1.42, 95% CI 1.10-1.83, respectively). Among women using HRT, however, there was no association observed between family history and cancer detection (moderate: OR=0.98, 95% CI 0.65-1.48; strong: OR=1.17, 95% CI 0.68-2.02) with history. The histological features of invasive tumours were similar among family history groups. CONCLUSIONS: Greater cancer detection rates and high proportions of invasive tumours with good prognosis indicate that women aged 50 and over with a family history may have the potential to benefit from regular breast cancer screening. Further studies are required to identify optimal screening guidelines and to examine whether HRT reduces the ability to detect cancer in these women.

Breast Neoplasms↗
PubMed1997

Prospective evaluation of prostate specific antigen density and systematic biopsy for detecting prostate cancer in Japanese patients with normal rectal examinations and intermediate prostate specific antigen levels.

PURPOSE: To improve the specificity of cancer detection in patients with normal digital rectal examination and intermediate prostate specific antigen (PSA) level, PSA density has been recommended, with biopsy based on a PSA density of 0.15 or more. PSA density is reportedly higher in Japanese men than in white men, because of physiological differences between the 2 races. We prospectively evaluated PSA density as a discriminator of prostate cancer in Japanese men. MATERIALS AND METHODS: We evaluated prospectively 60 consecutive men with normal digital rectal examinations and serum PSA levels of 4.1 to 10.0 ng./ml. enrolled during a 17-month period. All patients underwent transrectal ultrasound guided sextant biopsies, regardless of calculated PSA density and transrectal ultrasound findings. Serum PSA levels were determined by IMx assay. RESULTS: Overall, 8 of 60 men (13%) had prostate cancer. There was no significant difference in mean PSA between those with positive and those with negative biopsies, but the difference was significant in the mean PSA density (mean 0.24 and 0.15, respectively, p < 0.01). Receiver operating characteristics curves for PSA and PSA density demonstrated superior benefit for PSA density in this patient population. A reference PSA density value of 0.19 was chosen because it showed the highest sum of sensitivity and specificity, which gave a sensitivity of 75%, a specificity of 87%, a positive predictive value of 46% and a negative predictive value of 96%. CONCLUSIONS: The results suggest that PSA density improves the specificity of cancer detection in men with a normal digital rectal examination and an intermediate PSA level. Although further study with a larger patient population is needed to obtain a best-fit value, an optimal PSA density cutoff seems to be higher than that recommended in the literature from western countries. Because of possible racial differences in serum PSA and prostate volume, the role of PSA density in Asian men should be studied independently.

Aged↗
PubMed1989

[Limitations and possibilities of detecting lung cancer by fluoroscopic screening of the population].

In 10th district of Budapest a longitudinal, epidemiological examination was started in 1975 with the aim of analysis of the objective factors influencing the population screening and determination of possibilities of screening effectiveness. It was found that effectiveness of lung cancer detection with screening depends on the tumour cell-type, as well as on the localization being in connection with same. By computer method based on mathematical modelling the population can be divided into the following groups: risk-free, moderate-risk, high-risk and superhigh risk groups. The screening was said to be absolutely unnecessary in risk free groups and in case of persons over the age of 70 irrespective of their risk factor status. The material savings resulting from the reduction of screenings can be assigned to introduction of complex methods. The switch-over from quantitative screening to the qualitative one can increase the effectiveness of lung cancer detection.

Fluoroscopy↗