[Show abstract][Hide abstract] ABSTRACT: The EGF/IGF growth factors are potent mitogens that regulate cell proliferation and cell survival and are involved in prostate cancer development. Using laser microdissection technology and real-time PCR, together with immunohistochemistry, we have explored the growth factor and integrin dependent PI3-kinase/PTEN/Akt signalling pathway in prostate cell lines and tumour samples by analysing EGF-R, IGF1-R, ILK, beta3 integrin, PTEN and p-Akt protein expression. We provide evidence that loss of PTEN expression rather than upregulated EGF/IGF1 receptor expression was responsible for increased p-Akt in neoplastic prostate cells. We therefore compared PTEN expression in patient biopsies at first time diagnosis recruited prospectively (Study I, 112 patients) and patients with confirmed metastasis recruited retrospectively from the Luxembourg cancer registry (Study II, 42 patients). In Study I, loss of PTEN expression at first time diagnosis was found in 26 of 112 patients (23%). In Study II, 25 of the 42 patients (59%) with lymph node metastasis had complete loss of PTEN expression in both the neoplastic glands of the prostate and the invasive prostate cancer cells in the lymph node, and of these 13 (52%) exhibited already loss of PTEN expression at first diagnosis. These findings demonstrate that loss of PTEN expression is an important factor in progression towards metastatic disease and could potentially serve as an early prognostic marker for prostate cancer metastasis.
International Journal of Cancer 03/2007; 120(6):1284-92. DOI:10.1002/ijc.22359 · 5.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Twenty years after the nuclear accident in Chernobyl (Eastern Europe), there is still a controversial debate concerning a possible effect of the radioactive iodines, especially I-131, on the increase of thyroid carcinomas (TCs) in Western Europe. Time trends in incidence rates of TC in Luxembourg in comparison with other European countries and its descriptive epidemiology were investigated.
The population-based data of the national Morphologic Tumour Registry collecting new thyroid cancers diagnosed between 1983 and 1999 at a nation-wide level in the central division of pathology were reviewed and focused on incidence rates of TC. Data from 1990 to 1999 were used to evaluate the distribution by gender, age, histological type, tumour size and the outcome.
Out of 310 new thyroid carcinomas diagnosed between 1990 and 1999, 304 differentiated carcinomas (A: 80% papillary; B: 14.5% follicular; C: 3.5% medullary) and 6 anaplastic/undifferentiated TCs (D: 2%) were evaluated. The M/F-ratio was 1:3.2, the mean age 48.3 years (range: 13-92). The overall age-standardized (world population) incidence rates over the two 5-year periods 1990-1994 and 1995-1999 increased from 7.4 per 100,000 to 10.1 per 100,000 in females, from 2.3 per 100,000 to 3.6 per 100,000 in males. Only 3 patients were children or adolescents (1%), the majority of the patients (50%) were between 45 and 69 years of age. The percentage of microcarcinomas (<1 cm) was A: 46.4%, (115/248); B: 13.3%, (6/45); C: 27.3%, (3/11). The unexpected increase of TCs in 1997 was mainly due to the rise in the number of microcarcinomas. The observed 5-year survival rates for both genders were A: 96.0+/-2%; B: 88.9%; C: 90.9%; D: 0%. Prognosis was good in younger patients, worse in males and elderly, and extremely poor for undifferentiated TCs.
The increasing incidence rates of TC, especially of the papillary type, seem mainly due to a rise in diagnosed microcarcinomas due to some extent to a change in histologic criteria and to more efficient diagnostic tools. This rise appears to be independent of the number of surgical treatments, the immigration rate, and the Chernobyl fallout as the incidence of TC in children remained stable.
BMC Cancer 04/2006; 6:102. DOI:10.1186/1471-2407-6-102 · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A major technical challenge related to gene expression profiling of tissue samples is the difficulty of procuring selected cell populations from tissues that by nature are heterogeneous, such as prostate tissue. In this study we have examined the expression of integrin-linked kinase (ILK) mRNA in prostate adenocarcinoma cells versus normal prostate epithelial cells in order to determine whether ILK could be used as a reference marker gene for prostate adenocarcinoma cell mRNA isolation. Using laser microdissection (LMD) technology and real-time PCR, together with immunohistochemistry, we have analyzed ILK mRNA expression in epithelial cells isolated from frozen prostate biopsy specimens as well as 4 prostate cell lines (RWPE-1, LNCaP, PC-3 and DU 145) and correlated ILK mRNA expression with ILK protein expression. We demonstrate that quantitative upregulation of ILK mRNA expression in prostate epithelial cells derived from prostate tissue correlated with ILK protein expression and with the histopathology diagnosis of prostate adenocarcinoma. We further show that the level of ILK overexpression was directly influenced by the method used to isolate prostate adenocarcinoma cells (bulk tissue versus LMD dissected cells). These data provide evidence that ILK mRNA is quantitatively upregulated in prostate adenocarcinoma cells versus normal epithelial cells and is therefore a useful internal reference gene marker to evaluate the quality of prostate adenocarcinoma cell derived mRNA used for large scale prostate cancer cDNA gene profiling.
International Journal of Oncology 07/2005; 26(6):1549-58. DOI:10.3892/ijo.26.6.1549 · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Atypical glandular cells on cervical smears are often associated with clinically significant uterine lesions. The frequency and accuracy of AGC-NOS (i.e. atypical glandular cells, not otherwise specified) diagnoses, regardless of the gland cell type or the degree of suspicion, and their outcome were investigated.
From January 1, 1990 to December 31, 1999 a total of 261 patients had an AGC-NOS diagnosis made by conventional cervical Papanicolaou smear interpretation representing 0.05% of all Pap-smears analyzed at the national level. 191 (73.2%) patients had a subsequent histological examination, 8 samples were not representative by origin and were excluded.
Out of 183 AGC-NOS diagnosed, 56.3% (103/183) were associated with tissue-proven precancerous and/or cancerous lesions, 44% being of endocervical and 56% of endometrial origin. 75% of all AGC-patients were asymptomatic. 66.7% (6/9) of the patients with subsequent invasive endocervical adenocarcinoma (AC) and 56% (28/50) of those patients with invasive endometrial AC were without clinical symptoms. 3 patients out of 9 with an invasive endocervical AC were 35 years of age or less. 10.1% and 12.3% of all 'new' tissue-proven invasive endocervical or endometrial AC respectively recorded by the national Morphologic Tumour Registry (MTR) were first identified by a cytological AGC-NOS diagnosis.
Our findings emphasize the importance of the cytological AGC-category even in the absence of a precise origin or cell type specification. 56% of the AGC-diagnoses being associated with significant cancerous or precancerous conditions, a complete and careful evaluation is required.
BMC Cancer 08/2004; 4:37. DOI:10.1186/1471-2407-4-37 · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: For quality assurance purposes, the results of the 1990's obtained by the National Cervical Cancer Screening Programme (NCCSP) launched in 1962 were reviewed. The positive cytodiagnosis, the histologically verified in situ and invasive cervical cancers and the mortality rates were reported.
[Show abstract][Hide abstract] ABSTRACT: For quality assurance purposes, the frequency of 'abnormal' cytological diagnoses of the non-systematic National Cervical Cancer Screening Programme (NCCSP) was evaluated. In 1999, an unexpected high number of Class (Cl) III cases (i.e. atypical squamous cells of undetermined significance) was reported. The cytological and histological results were reviewed in order to detect a possible cause for this threefold increase. The abnormal Papanicolaou (PAP) smears examined by conventional methods from 1 January 1990 to 31 December 2002 were analysed. The smears of 682 cases diagnosed in 1999 with a Cl III category were reviewed in 2000 and correlated with the available histological diagnoses provided by the Central Department of Pathology. Of the 682 Cl III cases, 176 cases (26.1%) had no follow-up, 314 cases (46.0%) had repeat cytology and 192 cases (28.2%) an histological correlate corresponding to 90 (46.9%) benign lesions, 78 (40.6%) squamous intraepithelial lesions, two (1%) invasive cervical cancers (one squamous and one glandular). Twenty-two Cl III cases (11.5%) were histologically within normal limits. Retrospective smear review confirmed 330 Cl III diagnoses (48.3%), 127 cases (18.6%) were recategorized as Cl IIIG (i.e. atypical glandular cells of undetermined significance), 22 cases (3.2%) as Cl IIID (i.e. mild to moderate dysplasia) and six cases (0.9%) as Cl IVa (i.e. severe dysplasia and/or carcinoma in situ). A total of 197 original Cl III cases had to be reclassified in the Cl II category (28.9%), only two cases showing mild and moderate dysplasia on histology. Thus, 195 cases (28.6%) comprised cytological overdiagnoses. The Cl III category being, by definition, a delicate and often subjective diagnosis, all external influences such as pressure of litigation should be avoided to reduce cytological overdiagnoses as a result of an unnecessary 'fear-factor'.