Biomedical subjects

Aasmund Berner

Publications and source records attributed to Aasmund Berner.

At least 37 records · Page 2Linked to original sources

PubMed2004

[Fine needle cytology of the thyroid gland].

BACKGROUND: Application of fine needle cytology (FNC) is important in the preoperative assessment of thyroid lesions. The method is rapid, minimally invasive and cost effective. The aim of this study was to evaluate the role of fine needle cytology at The Norwegian Radium Hospital in the management of thyroid nodules. MATERIAL AND METHODS: Data on FNC and comparable histology results were retrieved from the pathology database during the 5-year-period 1998 through 2003. 1770 FNC samples and corresponding histology results from 443 lesions were compared. Reviews of cytological slides were done in 39 discrepant cases and quality assessment parameters calculated. RESULTS: High complete sensitivity (77.5%) and specificity (90.1%) were found. The false positive rate was 1.2% and the false negative rate 23.7%. Inadequate FNCs were particularly seen in submitted specimens. A review of the discrepant cases showed that the main cause of false negative samples was sampling error. Micropapillary carcinoma was the predominant tumour type with false negative FNC. Eleven malignancies were diagnosed in repeat FNC specimens. INTERPRETATION: FNC is a highly reliable test to assess whether a thyroid nodule is benign or malignant. Diagnostic pitfalls are mainly due to inability to procure the diagnostic material.

Biopsy, Fine-Needle↗

PubMed2004

NY-ESO-1 protein expression and humoral immune responses in prostate cancer.

BACKGROUND: Due to restricted expression in normal tissues cancer/testis (C/T) antigens represent candidate molecules for immunotherapy of cancer. NY-ESO-1 is a well-studied C/T antigen with unknown expression and immunogenicity in prostate cancer (PC) patients. METHODS: NY-ESO-1 expression was determined by immunohistochemistry and humoral immune responses against NY-ESO-1 assessed by enzyme-linked immuno-sorbent assay (ELISA) and Western blotting. Protein expression and serological responses were correlated with clinical findings and survival. RESULTS: NY-ESO-1 expression was found in biopsies from 2 of 66 localized PC and 7/48 hormone refractory prostate cancer (HRPC) patients, respectively. Anti-NY-ESO-1 antibodies were detected in sera from 1 of 112 localized PC and 18 of 95 HRPC patients. Two of four HRPC patients with NY-ESO-1 positive biopsies had mounted a serological response. Positive anti-NY-ESO-1 titers were correlated with poor survival in HRPC patients. CONCLUSIONS: NY-ESO-1 is expressed in a subset of HRPC patients and, together with other C/T antigens, may serve as a target antigen for development of immunotherapy of PC. Spontaneous serological responses against NY-ESO-1 may be associated with poor survival.

Adult↗

PubMed2004

The role of flow cytometric immunophenotyping in improving the diagnostic accuracy in referred fine-needle aspiration specimens.

Flow cytometric (FCM) immunophenotyping has an important role in the diagnostic work up of fine-needle aspiration (FNA) specimens obtained from lymphoid lesions. The objective of the present study was to evaluate the feasibility of this method with respect to referred FNA specimens. One hundred and two FNA specimens referred to our laboratory for FCM analysis during the last 3 years were studied. Specimens were sent, accompanied by cytological smears, from 11 distant hospitals by ordinary mail. The evaluation of potential B-cell monoclonality, the main diagnostic issue to be resolved using FCM, was possible in 86 of these 102 cases. The remaining 16 samples could not be analyzed or adequately interpreted because of sparse or necrotic material. A monoclonal B-cell population was found in 17/86 satisfactory cases, of which 16 were histologically confirmed. Eight cases contained cells positive for the epithelial marker Ber-EP4 and were diagnosed accordingly as carcinomas. FCM analysis of specimens obtained with a clinical question of Hodgkin lymphoma or T-cell lymphomas did not yield definitive data. The time lapse between sampling and analysis (12-84 hr) did not affect the results. This probably was due to the fact that all aspirates were taken in Roswell Park Memorial Institute (RPMI) cell medium, supplemented with 50% fetal calf serum. In conclusion, this retrospective study establishes that it is possible, in the majority of cases, to refer FNA material for FCM immunophenotyping by mail, and that results regarding B-cell clonality in the case of small-cell lymphomas are reliable also after a transportation period of 3-4 days. Carcinoma may be similarly diagnosed and a diagnosis of lymphoma may be excluded in reactive proliferations. Cases with only a few atypical cells or specimens from patients suspected of having Hodgkin lymphoma or T-cell lymphomas are not suitable for analysis by FCM.

Biopsy, Fine-Needle↗

PubMed2004

Heparanase and basic fibroblast growth factor are co-expressed in malignant mesothelioma.

Heparanase is an endoglycosidase that degrades heparan sulfate (HS) in the extracellular matrix (ECM) and cell surfaces, and fulfills a significant role in cancer metastasis and angiogenesis. We evaluated the expression of heparanase and its possible association with the expression of angiogenic molecules in malignant mesothelioma (MM), and analyzed whether expression of these proteins is site-related (pleural vs peritoneal MM, solid lesions vs effusions). Sections from 80 MM (56 biopsies, 24 effusions) were analyzed for heparanase protein expression using immunohistochemistry (IHC). Sixty MM were of pleural origin, and 20 were peritoneal. Effusion specimens consisted of 6 peritoneal and 18 pleural effusions, while biopsies consisted of 14 peritoneal and 42 pleural lesions. Fifty-four specimens were additionally evaluated for expression of basic fibroblast growth factor (bFGF), interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) proteins using IHC. Microvessel density (MVD) was studied in 28 biopsies using an anti-CD31 antibody. mRNA expression of heparanase (HPSE-1), VEGF and the VEGF receptor KDR was analyzed in 23 effusions using RT-PCR. Heparanase protein expression was seen in 69/80 (86%) tumors. Of these, 35 showed combined membrane and cytoplasmic expression, 30 cytoplasmic expression, and four exclusively membrane expression. Both total (P = 0.001) and cytoplasmic (P = 0.002) expression was significantly higher in solid tumors compared to effusions. Protein expression of VEGF, IL-8 and bFGF was seen in 21/54 (39%), 22/54 (41%) and 44/54 (81%) specimens, respectively. Protein expression of bFGF was significantly higher in solid tumors (P < 0.001) and correlated with heparanase expression (P = 0.005). HPSE-1 and VEGF mRNA expression was detected in all 23 effusions using RT-PCR, while KDR mRNA was found in 12/23 MM. KDR mRNA expression correlated with that of both HPSE-1 (P = 0.005) and VEGF (P = 0.001). Our results document frequent expression of heparanase in MM, in agreement with the biological aggressiveness of this tumor. The co-expression of heparanase with bFGF is in agreement with the role of the former in releasing bFGF from the ECM. The concomitant reduction in protein expression of both molecules in effusions as compared to solid tumors, supports the hypothesis of a reduced need for pro-angiogenic stimuli in effusions, and may aid in defining tumor progression in this setting.

Adult↗

PubMed2004

The clinical role of the PEA3 transcription factor in ovarian and breast carcinoma in effusions.

Ets transcription factors play a central role in invasion and metastasis through regulation of synthesis of proteolytic enzymes and angiogenic molecules. The objective of this study was to investigate the role of PEA3 in tumor progression of ovarian and breast carcinoma metastatic to effusions, and to evaluate the expression of Ets-2 and Erg in ovarian carcinoma. Ovarian (83 malignant effusions, 102 corresponding solid lesions) and breast (33 malignant effusions, 40 corresponding solid lesions) carcinomas were evaluated for expression of PEA3 using mRNA in situ Hybridization (ISH). Expression of Ets-2 and Erg mRNA was analyzed in 50 ovarian carcinoma effusions using the same method. PEA3 mRNA expression was comparable at all sites in ovarian carcinoma (44 out of 83; 53% of effusions, 48 out of 102; 47% of solid tumors). PEA3 mRNA expression in effusions correlated with mRNA expression of the previously studied alphav (P = 0.022), alpha6 (P < 0.001) and beta1 (P < 0.001) integrin subunits, the matrix metalloproteinase (MMP) inducer EMMPRIN (P = 0.015) and interleukin-8 (IL-8) (P = 0.033). Erg and Ets-2 mRNA was expressed in 15 out of 50 (30%) and 18 out of 50 (36%) effusions, respectively, and co-localized with PEA3 (P = 0.017 for Erg, P = 0.004 for Ets-2). In breast carcinoma, PEA3 expression was seen in 19/40 (48%) of solid lesions, with a significant upregulation in corresponding effusions compared to primary tumors (24 out of 33; 73%, P = 0.038). PEA3 mRNA expression in effusions obtained prior to the institution of chemotherapy predicted significantly shorter overall survival in univariate analysis (24 vs 37 months, P = 0.03), with a similar trend for Erg (13 vs 30 months, P = 0.1). In conclusion, PEA3 is expressed at all anatomic sites in serous ovarian cancer and co-localizes with Erg, Ets-2 and several metastasis-associated molecules. PEA3 mRNA expression is a novel marker for tumor progression to malignant effusion in breast carcinoma, and predicts poor outcome in effusions sampled prior to therapeutic intervention in ovarian carcinoma. These findings support a biological role for Ets transcription factors in these malignancies and suggests that they may be targets for therapeutic intervention.

Base Sequence↗

PubMed2003

Definitive radiotherapy of prostate cancer: the possible role of staging lymphadenectomy.

PURPOSE: To evaluate the postradiotherapy 5-year cancer-specific (CSS), clinical progression-free (cPFS), and overall (OS) survival rates in patients with pN0 M0 prostate cancer (PC). METHODS: Between 1989 and 1996, 203 consecutive pN0 M0 PC patients (T1-2, 66; T3-4, 137) received conformal prostatic four-field radiotherapy (median target dose 66 Gy). Any hormone manipulation was delayed until clinical progression (growth of the primary tumor or development of distant metastases). RESULTS: After a median observation time of 87 months (range 11-156), 99 patients had relapsed clinically and 70 patients were dead, 37 of them as a result of prostate cancer. Five-year CSS, cPFS, and OS rates were, respectively, 90% (95% CI 86-94%), 64% (95% CI 57-71%), and 82% (95% CI 77-87%), with no difference of OS compared with age-matched males from the general population. Gleason score (< or =7A vs. > or =7B) and the T category predicted cPFS, whereas CSS was associated with Gleason score only. Preradiotherapy PSA failed to predict survival. Patients with T1-2 Gleason score < or =7A had a 97% 5-year CCS, as compared with 89% for all other patients. A median of eight lymph nodes (range 0-29) were described in the specimens from pelvic lymphadenectomy (LA). CONCLUSION: Despite still preliminary observations, our 5-year results challenge the use of combined hormone radiotherapy in patients who are proven to be pN0 by preradiotherapy LA; in particular, in patients with T1-2/Gleason score < or =7A, whereas the survival in all other patients with pN0 M0 prostate cancer may be improved by adjuvant androgen deprivation.

Aged↗

PubMed2003

[Fine-needle aspiration cytology or core biopsy when diagnosing tumours of the breast].

BACKGROUND: Fine-needle aspiration (FNA) biopsy is an established, highly accurate method for diagnosing breast lesions. In recent years, core biopsy (CB) has been increasingly used. The aim of this study was to compare the quality assessment parameters of FNA and CB in palpable and non-palpable breast lesions. METHODS: Data on FNA and CB results were retrieved from the pathology database and 4367 FNA samples and corresponding histology results from 1275 lesions were compared. Quality assessment parameters were calculated using the methodology detailed in the National Health Service breast screening programme guidelines. RESULTS: High absolute and complete specificity, absolute and complete sensitivity and low inadequate rates were found for CB compared with FNA. Low specificity for FNA was particularly seen in collagenous lesions and in submitted specimens sampled by doctors without particular experience with the FNA procedure. INTERPRETATION: CB may be an alternative method for preoperative diagnosis when experienced cytopathologists are not available. CB is superior to FNA in fibrotic and collagenous lesions such as lobular carcinoma and radial scar due to low cellularity. FNA is the more accurate method when an immediate assessment by a cytopathologist is performed for evaluation of adequate material so that additional aspirations can be done if needed.

Biopsy↗

PubMed2003

Fine-needle aspiration cytology vs. core biopsy in the diagnosis of breast lesions.

Fine-needle aspiration cytology (FNAC) is an established, highly accurate method for diagnosing breast lesions. However, in recent years there has been increased use of core biopsy (CB) in this setting. The aim of this study was to evaluate the accuracy of FNAC and compare the quality assessment parameters of FNAC and CB in palpable and nonpalpable breast lesions. Data regarding FNAC, CB, and excision biopsy (EB) diagnoses were retrieved from the archives of our department. A total of 4,367 FNAC samples from the years 1999-2001 was reviewed. Of these, corresponding histology results were available for 1,275 lesions, of which 1,248 were primary breast epithelial lesions (788 EB, 199 CB, 261 EB+CB). All cases were analyzed for sensitivity and specificity of FNAC. Cases with both FNAC and CB were compared and quality assessment parameters were calculated using the methodology detailed in the National Health Service Breast Screening Program guidelines. High specificity and sensitivity, as calculated for satisfactory specimens, were achieved with the use of both FNAC and CB. False-positive and false-negative diagnoses were seen in 7/404 (1.7%) and 45/635 (7.1%) of biopsy-proven specimens sampled by FNAC. The corresponding values for CB were 0% and 5.7%, respectively. Inadequate sampling (15.1%) with use of FNAC was particularly seen in collagenous lesions and in submitted specimens sampled by physicians lacking experience with the FNAC procedure. FNAC is a valuable method, although moderately less sensitive than CB. CB is the preferred method for preoperative diagnosis when sampling FNAC provides scarce material and suspicion of a fibrotic and collagenous lesion such as lobular carcinoma and radial scar arises. FNAC is most accurate when experienced cytologists are available and when immediate assessment by professionals is performed for evaluation of material adequacy, so that additional aspirations can be done when needed.

Adenocarcinoma↗

PubMed2003

Effusion cytology in ovarian cancer: new molecular methods as aids to diagnosis and prognosis.

Carcinoma of the ovary is the leading cause of death from gynecologic cancer in western countries. Ovarian carcinoma is commonly associated with the accumulation of fluid that contains malignant cells in the peritoneal and pleural cavities. This article details the current knowledge regarding the diagnostic and biologic characteristics of ovarian carcinoma cells in effusions, and the genotypic and phenotypic differences between solid primary tumors and metastatic lesions. Finally, we present a new approach, by which the analysis of fresh frozen viable cells allows us to study in vivo the links between expression and activity of extracellular mediators, membrane receptors, intracellular signaling, and transcription factors, and their potential therapeutic and prognostic significance.

Cell Biology↗

PubMed2003

Gonadal morphology and sex hormones in male and female Wistar rats after long-term lamotrigine treatment.

Drug-induced disturbances in reproductive hormones and gonadal morphology have been observed both in patients with epilepsy and in non-epileptic animals. Less is known about the influence of newer antiepileptic drugs including lamotrigine on reproduction. Lamotrigine is now increasingly used both in epilepsy and psychiatric disorders. Sixty-five Wistar rats were fed by gastric tube either 5 mg kg(-1) lamotrigine solution (males=15, females=20) or 0 (vehicle control, males=15, females=15) twice daily for 90 days. In males, no significant differences were found in body or testicular weight. Testicular atrophy was observed in one control animal and in two of the rats receiving lamotrigine. No morphological changes were seen in the other organs investigated (liver, kidney, pancreas, brain, lymphatic tissue, heart). None of the animals showed over-expression of p53. No significant differences were observed between the control rats and the male rats receiving lamotrigine regarding testosterone, FSH and LH. In females, no changes in ovarian morphology or alterations in other tissues were observed. Serum testosterone, FSH, LH, insulin and progesterone remained unchanged in the lamotrigine treated animals, while serum estrogen was significantly reduced.

Animals↗

PubMed2003

EMMPRIN (extracellular matrix metalloproteinase inducer) is a novel marker of poor outcome in serous ovarian carcinoma.

EMMPRIN is a member of the immunoglobulin superfamily of adhesion molecules and has a role in the activation of several matrix metalloproteinases (MMP). The objective of this study was to investigate the expression of EMMPRIN in effusions, primary and metastatic tumors of serous ovarian carcinoma patients, as well as to evaluate its association with clinicopathologic parameters and with MMP and integrin expression. Eighty effusions and eighty-three solid lesions were evaluated for expression of EMMPRIN mRNA using in situ hybridization (ISH). Protein expression was studied in 75 effusions and 55 biopsies using immunohistochemistry (IHC). EMMPRIN mRNA and protein were detected in carcinoma cells in 63/80 (79%) and 64/75 (85%) effusions, respectively. Expression was similar in peritoneal and pleural effusions. EMMPRIN was co-expressed with MMP-1 (P < 0.001), MMP-9 (P = 0.006) and the alphav (P = 0.013) and beta1 (P = 0.029) integrin subunits. In solid lesions, EMMPRIN localized most often to tumor cells (51/83 using ISH, 51/55 using IHC), but was also expressed in stromal and endothelial cells in approximately one third of the cases. EMMPRIN mRNA expression in tumor cells was most frequent in peritoneal metastases (P = 0.03). EMMPRIN expression in carcinoma cells of solid tumors showed an association with that of MMP-9 (P = 0.018), while labeling of stromal cells showed co-localization with the beta1 integrin subunit (P = 0.043). In survival analysis, EMMPRIN protein expression in stromal cells of primary tumors (P = 0.012) and in endothelial cells of all solid tumors (P = 0.023) correlated with poor survival. In conclusion, EMMPRIN is a novel prognostic marker in ovarian carcinoma, and is co-expressed with other metastasis-associated molecules in this malignancy. The identical phenotype of carcinoma cells in pleural and peritoneal effusions provides further evidence to our theory that cells at these sites share similar genotypic and phenotypic profiles.

Adult↗

PubMed2002

Independent prognostic significance of HER-2 oncoprotein expression in pN0 prostate cancer undergoing curative radiotherapy.

Existing prognostic algorithms for localized prostate cancer (PC) are hampered by poor validation for endpoints other than biochemical relapse such as clinical disease progression or survival. Therefore, the prognostic relevance of Her-2 (Her-2/neu, c-erbB2) protein expression in patients undergoing curative radiotherapy (RT) was compared to widely accepted prognostic factors such as pretreatment prostate-specific antigen (PSA) levels, biopsy Gleason score and T category of the primary tumor. Biopsies from 112 homogeneously treated patients with T1-4pN0M0 PC were examined by immunohistochemistry and 37% of cases showed membrane-bound Her-2 expression in more than 10% of cancer cells. No definite membrane staining was seen in normal prostate epithelium. With 25 patients dead of PC and a median follow-up of surviving patients of 71 months (range 48-144), the prognostic relevance of Her-2 expression was univariately associated with adverse outcome in terms of biochemical or clinical progression-free survival (B/C-PFS; p = 0.04), clinical progression-free survival (C-PFS; p = 0.02) and disease-specific survival (DSS; p = 0.02). In multivariate analysis, Her-2 expression, T category and Gleason score were independently associated with C-PFS, whereas only Her-2 expression and Gleason score were associated with DSS. Her-2 expression and Gleason score together discriminated 2 groups of patients with 5-year DSS of 95% and 79%, respectively (p < 0.001). Pretreatment PSA levels were associated only with B/C-PFS but not with C-PFS or DSS. Together the data show for the first time that expression of Her-2 is of prognostic relevance in localized PC undergoing RT and suggest that analysis for Her-2 may improve prognostic algorithms for clinically relevant endpoints other than biochemical relapse.

Adenocarcinoma↗

PubMed2002

Fine-needle aspiration cytology of lobular carcinoma in situ.

Fine-needle aspiration cytology (FNAC) plays a key role in the preoperative diagnosis of breast carcinoma but is less reliable in the diagnosis of in situ lesions. The objective of the present study was to investigate the cytological features of lobular carcinoma in situ (LCIS), regarding which little data is available to date. Cytological features of FNAC of the breast from 21 patients with histology-proven LCIS were described and compared with surgical specimens. Aspirates from 8/21 cases had cell groups diagnostic for or compatible with LCIS. Aspirates from an additional two cases demonstrated hypercellular, dissociated, and more pleomorphic tumor cells, which were originally diagnosed as invasive lobular carcinoma (ILC). The remaining 11 aspirates were diagnosed as benign or nondiagnostic. FNAC from the eight diagnostic specimens were characterized by loosely cohesive cell groups composed of uniform cells with occasional intracytoplasmic lumina, slightly irregular and eccentric nuclei. We conclude that the main difficulty in diagnosing LCIS by FNAC is sampling rather than recognition of the lesions. However, one should be aware of the cytological features of LCIS in order to reach a correct diagnosis. There are no reliable cytological criteria that help in differentiating pleomorphic and dissociated LCIS from ILC.

Adult↗

PubMed2002

Cystic change in metastatic lymph nodes: a common diagnostic pitfall in fine-needle aspiration cytology.

Fine-needle aspiration cytology (FNAC) of cystic metastases is a challenging diagnostic category and has been investigated in a limited number of malignancies and sites. The present study retrospectively reviewed 1,211 FNAC of superficial masses, including lymph nodes (1,102 aspirates), benign cystic lesions (64 aspirates), and lymphocysts (45 aspirates) with the aim of determining the tumors that cause cystic change in metastases. Cytology results from 1,102 lymph node aspirations were suspicious or positive for malignancy in 541 specimens (49.1%), benign in 230 (20.9%), and unsatisfactory in 331 (30%). There were 28 malignant aspirates demonstrating cystic change (5.2%). The tumor type that most frequently caused cystic change was thyroid papillary carcinoma (42.8% of cases), followed by squamous cell carcinoma (primary in the head and neck region 30.8% and in the skin 24%), tumors of unknown origin (6.3%), serous papillary carcinoma of the ovary or endometrium (4.8%), and malignant melanoma (2.1%). Cystic change was observed most commonly in the head and neck region lymph nodes (60%). The most challenging lesions to assess using FNAC were metastatic lymph nodes showing cystic change, accounting for six of the 16 false-negative diagnoses and one false-positive diagnosis. The results of this study suggest that cystic change in metastatic lymph nodes occurs in certain types of tumors and is an important cause of diagnostic error. FNAC should be repeated in case of suspicious hypocellular cystic aspirations, especially in patients with known malignancy.

Adult↗

PubMed2002

Ultrasound-guided fine needle cytology of retroperitoneal masses in patients with malignant germ cell tumours: diagnosis and therapeutic impact.

PURPOSE: There are few reports on the use of fine needle cytology (FNC) for the detection of retroperitoneal lymph node metastases from malignant germ cell tumours (MGCT). In order to determine efficiency of the procedure and its impact on therapeutic approaches, this study reviews experience with ultrasound-guided transabdominal FNC in patients with MGCT. PATIENTS AND METHODS: Twenty-four patients with known malignant germ cell tumour and four patients without previous histology, presented with retroperitoneal masses. They underwent ultrasound-guided fine needle cytology (aspirations were done twice in two patients). Clinical data were retrieved from the medical records and all cytological specimens were reviewed. In metastatic cases, the cytologic findings were correlated with the histology of the primary tumour. RESULTS: Twenty-one of 30 specimens (70%) were diagnosed as malignant, 6 (20%) were benign, and 3 (10%) were unsatisfactory for the cytologic diagnosis. Five of the 21 malignant lesions were < or =10mm. FNC yielded the correct diagnosis in all four cases of extragonadal malignant germ cell tumours. In four other patients, FNC solved significant staging problems at the diagnosis. In 7 of 11 patients with the suspicion of retroperitoneal recurrence and normal serum tumour markers during follow-up, FNC confirmed the malignant morphology of the lesions. CONCLUSIONS: In experienced hands, ultrasound-guided FNC can be a valuable method for the morphological diagnosis of retroperitoneal manifestations from MGCT. FNC should be added in follow-up and staging procedures (radiological imaging and serum tumour markers) in selected patients in whom the histological verification of such lesions is critical for the patient's management.

Adolescent↗

PubMed2002

Interleukin-8 and vascular endothelial growth factor mRNA and protein levels are down-regulated in ovarian carcinoma cells in serous effusions.

Angiogenic factors are involved in tumor growth and spread. The aim of this study was to evaluate the expression of angiogenesis-related genes in malignant serous effusions of patients with advanced-stage (FIGO stage III and IV) ovarian carcinoma. In addition, to compare the results for carcinoma cells in effusions with corresponding primary tumors and metastatic lesions, and analyze their prognostic role. Sections from 66 effusions and 90 primary and metastatic lesions from 62 ovarian and primary peritoneal carcinoma patients, were evaluated for expression of basic fibroblast factor (bFGF), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) using mRNA in situ hybridization (ISH). Protein expression was evaluated in a subset of specimens using immunohistochemistry (IHC). ISH results were correlated with clinical parameters. In both effusions and solid tumors, bFGF mRNA was the most commonly expressed factor (93% of effusions and 95% of solid tumors) followed by IL-8, while VEGF was expressed in a minority of the specimens (P < 0.001 for bFGF vs. IL-8 and VEGF). In solid tumors, angiogenic mRNA expression was seen in both tumor and stromal cells in the majority of positive cases. ISH results did not differ in primary and metastatic tumors. However, carcinoma cells in effusions showed down-regulated expression of VEGF, when compared with both primary tumors (P = 0.029) and metastases (P = 0.015). IL-8 showed a similar down-regulation in effusions, when compared with metastases (P = 0.005). IHC showed excellent agreement with mRNA findings on protein level. In the study of clinico-pathologic parameters, IL-8 mRNA expression in effusions was associated with higher tumor grade (P = 0.044). Angiogenic gene expression in effusions showed no correlation with patient age, previous treatment, residual tumor size, FIGO stage or disease outcome in survival analysis (P > 0.05). Peritoneal and pleural effusions showed similar expression patterns. In conclusion, bFGF is the major angiogenic factor expressed in ovarian carcinoma at the mRNA level. It is highly expressed in both solid tumors and serous effusions, while IL-8 and VEGF are down regulated in carcinoma cells in effusions, possibly due to the lack of interaction with stromal cells. mRNA expression of VEGF, bFGF, and IL-8 does not appear to be a predictor of disease outcome in advanced-stage ovarian carcinoma. Carcinoma cells in pleural and peritoneal effusions show a similar metastatic expression profile, in agreement with our previous findings, supporting the true metastatic nature of ovarian carcinoma cells in ascites.

Ascitic Fluid↗

PubMed2002

Cell cycle inhibitors and outcome after radiotherapy in bladder cancer patients.

The aim of this study was to correlate the expression of cell cycle inhibitors with outcome of patients with muscle-invasive bladder cancer treated with preoperative radiotherapy (46 Gy/4-5 weeks or 20 Gy/1 week) and cystectomy. Patients with pT3b (n = 42) or pT0 (n = 17) were included in the study. Expression of p16INK4a and p27KIP1 was assessed immunohistochemically in pre-radiotherapy biopsies and cystectomy specimens. Previously reported results of p21CP1 expression were also included. No difference in pretreatment protein expression was found between patients with pT0 and pT3b. Expression of p21CIP1 and p27KIP1 was lower in cystectomy specimens than in pretreatment biopsies. None of the proteins showed significant impact on survival when analysed separately. However, patients with tumours showing > 50% expression of p16INK4a, p21CIP1, or p27KIP1 displayed poorer cancer-specific survival rates compared with the remaining patients (p = 0.025). This effect was more pronounced in patients receiving 46 Gy than in those receiving 20 Gy. In conclusion, low expression of cell cycle inhibitors is related to favourable survival after pre-cystectomy radiotherapy.

Carcinoma, Transitional Cell↗

PubMed2002

Detection of malignant epithelial cells in effusions using flow cytometric immunophenotyping: an analysis of 92 cases.

We compared the efficiency of immunophenotyping using flow cytometry (FCM) and a combination of morphologic and immunocytochemical studies for detecting malignant cells in 92 effusions. Cytologic results were as follows: carcinoma cells, 43 specimens; benign, 42 specimens; suggestive of nonepithelial malignancy, 7 specimens. After immunocytochemical analysis, 5 benign specimens were reclassified as malignant and 4 malignant epithelial specimens as benign. With FCM, cells positive for Ber-EP4, B 72.3, AH6, and HB-TN were detected in 28 to 36 (64%-82%) of 44 carcinomas but only 2 to 12 (5%-29%) of 41 benign specimens. Significant association was seen for coexpression. Ber-EP4 and AH6 were the most sensitive; Ber-EP4 was the most specific. The presence of cells positive for 3 of 4 markers strongly suggested malignancy (34/44 carcinoma specimens [77%]; 3/41 reactive specimens [7%]). The presence of cells positive for all 4 markers was diagnostic of malignancy (17/44 malignant specimens [39%]; 0/41 reactive effusions [0%]). FCM and immunocytochemical resultsfor Ber-EP4 expression showed excellent association. FCM is a powerful tool for diagnosing difficult effusions and can quantify coexpression of various markers in fresh specimens. By using established cellular markers coupled with biological markers, FCM also has great promise for experimental purposes.

Antibodies, Monoclonal↗