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1.
Breast Cancer Res Treat ; 90(1): 85-91, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15770531

ABSTRACT

BACKGROUND: Reports on long-term outcomes after endoscopic axillary lymph node dissection (ALND) of breast cancer patients are still lacking in the medical literature. The objective of this prospective study was to assess the oncological and functional outcomes in breast cancer patients after endoscopic ALND. METHODS: Fifty-five breast cancer patients were prospectively enrolled, of whom 52 were available for follow-up with a median of 71.9 months (range 11-96). The following oncological and functional endpoints were evaluated during follow-up at several time points: occurrence of local, axillary and distant metastases, seroma or infection, shoulder mobility (range of motion), numbness, pain, presence of lymphoedema as well as restriction in activities of daily living. RESULTS: In 52 patients endoscopic ALND of level I and II was successfully performed. Two port-site metastases (2/52, 4%) occurred, one of which in a patient with negative axillary lymph nodes. The same patient suffered from the only axillary recurrence (1/52, 2%). Three patients (3/52, 6%) developed lymphoedema. No other functional adverse events (shoulder mobility, pain, numbness, hypertrophic scar) were noticed at the end of the observation period. CONCLUSION: The present investigation with long-term follow-up after endoscopic ALND--the first one in the literature--reveals minor morbidity, good functional and cosmetic results. In contrary to conventional surgery, the endoscopic procedure is associated with the occurrence of port-site metastases, not seen in the open approach. Axillary recurrences do not appear more frequently when compared with results after conventional ALND. In the meantime the less invasive sentinel lymph node (SLN) biopsy is the established standard technique in evaluating the axillary lymph node status.


Subject(s)
Breast Neoplasms/surgery , Endoscopy , Lymph Node Excision , Activities of Daily Living , Adult , Aged , Aged, 80 and over , Axilla , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms/secondary , Female , Humans , Lymphedema/epidemiology , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Postoperative Complications/epidemiology , Prospective Studies , Switzerland/epidemiology , Treatment Outcome
2.
Am J Pathol ; 159(6): 2249-56, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11733374

ABSTRACT

Advances in genomics and proteomics are dramatically increasing the need to evaluate large numbers of molecular targets for their diagnostic, predictive or prognostic value in clinical oncology. Conventional molecular pathology techniques are often tedious, time-consuming, and require a lot of tissue, thereby limiting both the number of tissues and the number of targets that can be evaluated. Here, we demonstrate the power of our recently described tissue microarray (TMA) technology in analyzing prognostic markers in a series of 553 breast carcinomas. Four independent TMAs were constructed by acquiring 0.6 mm biopsies from one central and from three peripheral regions of each of the formalin-fixed paraffin embedded tumors. Immunostaining of TMA sections and conventional "large" sections were performed for two well- established prognostic markers, estrogen receptor (ER) and progesterone receptor (PR), as well as for p53, another frequently examined protein for which the data on prognostic utility in breast cancer are less unequivocal. Compared with conventional large section analysis, a single sample from each tumor identified about 95% of the information for ER, 75 to 81% for PR, and 70 to 74% for p53. However, all 12 TMA analyses (three antibodies on four different arrays) yielded as significant or more significant associations with tumor-specific survival than large section analyses (p < 0.0015 for each of the 12 comparisons). A single sample from each tumor was sufficient to identify associations between molecular alterations and clinical outcome. It is concluded that, contrary to expectations, tissue heterogeneity did not negatively influence the predictive power of the TMA results. TMA technology will be of substantial value in rapidly translating genomic and proteomics information to clinical applications.


Subject(s)
Biomarkers/analysis , Breast Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Breast Neoplasms/metabolism , Female , Humans , Immunohistochemistry , Middle Aged , Prognosis , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Survival Analysis , Tumor Suppressor Protein p53/analysis
3.
Anal Cell Pathol ; 22(4): 229-34, 2001.
Article in English | MEDLINE | ID: mdl-11564899

ABSTRACT

Multiple regions of the genome are often amplified during breast cancer development and progression, as evidenced in a number of published studies by comparative genomic hybridization (CGH). However, only relatively few target genes for such amplifications have been identified. Here, we indicate how small-scale commercially available cDNA and CGH microarray formats combined with the tissue microarray technology enable rapid identification of putative amplification target genes as well as analysis of their clinical significance. According to CGH, the SUM-52 breast cancer cell line harbors several high-level DNA amplification sites, including the 10q26 chromosomal region where the fibroblast growth factor receptor 2 (FGFR2) gene has been localized. High level amplification of FGFR2 in SUM-52 was identified using CGH analysis on a microarray of BAC clones. A cDNA microarray survey of 588 genes showed >40-fold overexpression of FGFR2. Finally, a tissue microarray based FISH analysis of 750 uncultured primary breast cancers demonstrated in vivo amplification of the FGFR2 gene in about 1% of the tumors. In conclusion, three consecutive microarray (CGH, cDNA and tissue) experiments revealed high-level amplification and overexpression of the FGFR2 in a breast cancer cell line, but only a low frequency of involvement in primary breast tumors. Applied to a genomic scale with larger arrays, this strategy should facilitate identification of the most important target genes for cytogenetic rearrangements, such as DNA amplification sites detected by conventional CGH. Figures on http://www.esacp.org/acp/2001/22-4/heiskanen.htm


Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/metabolism , DNA, Complementary/metabolism , Genetic Techniques , Nucleic Acid Hybridization , Oligonucleotide Array Sequence Analysis , Receptor Protein-Tyrosine Kinases/biosynthesis , Receptor Protein-Tyrosine Kinases/genetics , Receptors, Fibroblast Growth Factor/biosynthesis , Receptors, Fibroblast Growth Factor/genetics , Chromosomes, Human, Pair 10 , Female , Humans , In Situ Hybridization, Fluorescence , Receptor, Fibroblast Growth Factor, Type 2
4.
J Natl Cancer Inst ; 93(15): 1141-6, 2001 Aug 01.
Article in English | MEDLINE | ID: mdl-11481385

ABSTRACT

BACKGROUND: Only 25% of patients with HER-2/neu-positive metastatic breast tumors respond favorably to trastuzamab (Herceptin) treatment. We hypothesized that a high failure rate of patients on trastuzamab could result if some of the metastases were HER-2 negative and these metastases ultimately determine the course of the disease. METHODS: We used tissue microarrays (TMAs) containing four samples each from 196 lymph node-negative primary tumors, 196 lymph node-positive primary tumors, and three different lymph node metastases from each lymph node-positive tumor to estimate HER-2 gene amplification by fluorescence in situ hybridization (FISH) and Her-2 protein overexpression by immunohistochemistry (IHC). RESULTS: FISH and IHC analyses gave the same result with respect to HER-2 status for 93.7% of the tissues contained in the TMAs. Tissue samples were, therefore, considered to be HER-2 positive if they were positive for either HER-2 DNA amplification or Her-2 protein expression and HER-2 negative if both FISH and IHC gave a negative result. The HER-2 status of lymph node-positive primary tumors was maintained in the majority of their metastases. For HER-2-positive primary tumors, 77% (95% confidence interval [CI] = 59% to 90%) had entirely HER-2-positive metastases, 6.5% (95% CI = 8% to 21%) had entirely HER-2-negative metastases, and 16.3% (95% CI = 5% to 34%) had a mixture of HER-2-positive and HER-2-negative metastases. For HER-2-negative primary tumors, 95% (95% CI = 88% to 98%) had metastases that were entirely negative for HER-2. CONCLUSIONS: Our data suggest that differences in HER-2 expression between primary tumors and their lymph node metastases cannot explain the high fraction of nonresponders to trastuzamab therapy.


Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/pathology , Gene Amplification , Genes, erbB-2/genetics , Oligonucleotide Array Sequence Analysis , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/secondary , Carcinoma, Lobular/genetics , Carcinoma, Lobular/secondary , DNA, Neoplasm/analysis , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Lymphatic Metastasis , Oligonucleotide Array Sequence Analysis/methods , Trastuzumab , Up-Regulation
5.
Rofo ; 173(3): 224-8, 2001 Mar.
Article in German | MEDLINE | ID: mdl-11293864

ABSTRACT

PURPOSE: To compare the indications for biopsy with and without the use of the Breast Imaging Reporting and Data System. MATERIAL AND METHODS: Biopsies using the ABBI were performed in 62 patients with 64 non-palpable evident mammographic lesions. The initial decision for biopsy was made by non-radiologists due to suspicious microcalcifications (n = 53) and masses (n = 11). The indication was retrospectively reassessed by adopting the BI-RADS classification by three radiologists in consensus. The positive predictive value (PPV) of both indication strategies was assessed and compared. RESULTS: Biopsies adopting ABBI were performed without major side-effects and were diagnostic. Carcinoma was present in 14 lesions: nine specimens were diagnosed as DCIS and five as invasive carcinomas. For the 50 benign lesions histology revealed mastopathies (26/50) and fibroadenomas (8/50) as the most frequent diagnosis. The positive predictive value (PPV) for the initial indication was 22%, whereas PPV for BI-RADS based indications (categories 4 and 5) was 31%. CONCLUSION: ABBI enables stereotactically-guided procedures that result in representative and diagnostic biopsies. Standardized criteria like BI-RADS improve the PPV and should be a mandatory part of mammographic evaluation. Radiologists should remain involved in the decision making.


Subject(s)
Biopsy/instrumentation , Breast Neoplasms/pathology , Breast/pathology , Carcinoma in Situ/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma/pathology , Mammography , Adult , Aged , Breast Diseases/diagnosis , Breast Diseases/diagnostic imaging , Breast Diseases/pathology , Breast Neoplasms/diagnosis , Breast Neoplasms/diagnostic imaging , Calcinosis/diagnosis , Calcinosis/diagnostic imaging , Calcinosis/pathology , Carcinoma/diagnosis , Carcinoma/diagnostic imaging , Carcinoma in Situ/diagnosis , Carcinoma in Situ/diagnostic imaging , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Ductal, Breast/diagnostic imaging , Diagnosis, Differential , Female , Humans , Middle Aged , Palpation , Papilloma/diagnosis , Papilloma/diagnostic imaging , Papilloma/pathology , Predictive Value of Tests , Retrospective Studies , Stereotaxic Techniques , Time Factors
6.
Cancer Res ; 60(19): 5340-4, 2000 Oct 01.
Article in English | MEDLINE | ID: mdl-11034067

ABSTRACT

Studies by comparative genomic hybridization imply that amplification of the chromosomal region 17q22-q24 is common in breast cancer. Here, amplification and expression levels of six known genes located at 17q23 were examined in breast cancer cell lines. Four of them (RAD51C, S6K, PAT1, and TBX2) were found to be highly amplified and overexpressed. To investigate the involvement of these genes in vivo, fluorescence in situ hybridization analysis of a tissue microarray containing 372 primary breast cancers was used. S6K, PAT1, and TBX2 were coamplified in about 10% of tumors, whereas RADS1C amplification was seen in only 3% of tumors. Expression analysis in 12 primary tumors showed that RAD51C and S6K were consistently expressed in all cases in which they were amplified and also in some tumors without amplification. These data suggest that 17q23 amplification results in simultaneous up-regulation of several genes, whose increased biological activity may jointly contribute to the more aggressive clinical course observed in patients with 17q23-amplified tumors.


Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Chromosomes, Human, Pair 17/genetics , Saccharomyces cerevisiae Proteins , Adult , Aged , Aged, 80 and over , Blotting, Northern , DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/genetics , Female , Gene Amplification , Gene Expression , Gene Expression Profiling , Humans , In Situ Hybridization, Fluorescence , Middle Aged , Oncogene Proteins/biosynthesis , Oncogene Proteins/genetics , Oncogenes/genetics , Polymerase Chain Reaction , RNA-Binding Proteins , Rad51 Recombinase , Ribosomal Protein S6 Kinases/biosynthesis , Ribosomal Protein S6 Kinases/genetics , T-Box Domain Proteins/biosynthesis , T-Box Domain Proteins/genetics
7.
Cancer ; 89(3): 604-14, 2000 Aug 01.
Article in English | MEDLINE | ID: mdl-10931460

ABSTRACT

BACKGROUND: A new, internationally accepted histologic classification of renal cell carcinoma (RCC) and a new edition of the TNM staging system were introduced in 1997. In the latter, there was a dramatic change in the pT classification of organ-confined renal cancer in which the break point between category pT1 and pT2 was increased from 2.5 cm to 7 cm. METHODS: To study the significance of the new pT classification and the new recommendations for histologic classification, 588 nephrectomy specimens were reevaluated to define morphologic prognostic parameters in RCC. pT classification (TNM 1997), histologic subtype, histologic tumor grade, presence of necrosis, and sarcomatoid differentiation were assessed. RESULTS: The histopathologic review according to the new classification revealed 487 conventional (clear cell) (83%), 64 papillary (11%), 31 chromophobe (5%), and 6 collecting duct (1%) RCCs. Clinical follow-up was available for 470 RCCs. The new pT classification (1997) was strongly correlated with patient survival (P < 0.0001). Histologic grade, presence of necrosis, and sarcomatoid differentiation provided independent prognostic information on the clear cell subtype of renal cancer. Sarcomatoid differentiation, but not tumor necrosis, portended a dismal prognosis for patients with papillary RCC. Chromophobe RCC was associated with a significantly better prognosis than clear cell RCC (P = 0.05). Papillary RCC with scanty cytoplasm and small cells (type 1) behaved less aggressively than papillary tumors with eosinophilic cytoplasm and large cells (type 2; P < 0.001). CONCLUSIONS: Accurate histologic classification according to the new recommendations has implications because the prognostic importance of other histologic features that are of independent significance varies with tumor subtype. The data suggest that the new pT classification allows good separation of prognostic groups of patients with renal cancer.


Subject(s)
Carcinoma, Renal Cell/classification , Kidney Neoplasms/classification , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Humans , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Neoplasm Staging , Prognosis
8.
J Natl Cancer Inst ; 92(15): 1252-9, 2000 Aug 02.
Article in English | MEDLINE | ID: mdl-10922410

ABSTRACT

BACKGROUND: Studies by comparative genomic hybridization (CGH) have shown that chromosomal region 17q23 is amplified in up to 20% of primary breast cancers. We used microarray analyses to measure the expression levels of genes in this region and to explore their prognostic importance. METHODS: A microarray that contained 4209 complementary DNA (cDNA) clones was used to identify genes that are overexpressed in the MCF-7 breast cancer cell line as compared with normal mammary tissue. Fluorescence in situ hybridization was used to analyze the copy number of one overexpressed gene, ribosomal protein S6 kinase (S6K), and to localize it to the 17q23 region. Northern and western blot analyses were used to measure S6K gene and protein expression, and an enzymatic assay was used to measure S6K activity. Tumor tissue microarray analysis was used to study amplification of S6K and the HER-2 oncogene, another 17q-linked gene, and the relationship between amplification and prognosis was analyzed. The Kaplan-Meier method was used for data analysis, and the log-rank test was used for statistical analysis. All P values are two-sided. RESULTS: S6K was amplified and highly overexpressed in MCF-7 cells relative to normal mammary epithelium, and protein expression and enzyme activity were increased. S6K was amplified in 59 (8.8%) of 668 primary breast tumors, and a statistically significant association between amplification and poor prognosis (P =.0021) was observed. Amplification of both S6K and HER-2 implied particularly poor survival (P =.0001). CONCLUSIONS: The combination of CGH information with cDNA and tissue microarray analyses can be used to identify amplified and overexpressed genes and to evaluate the clinical implications of such genes and genomic rearrangements. S6K is likely to be one of the genes at 17q23 that is amplified during oncogenesis and may adversely affect the prognosis of patients with this amplification.


Subject(s)
Breast Neoplasms/enzymology , Breast Neoplasms/genetics , Chromosomes, Human, Pair 17/genetics , DNA, Neoplasm/analysis , Gene Expression Profiling/methods , Oligonucleotide Array Sequence Analysis , Ribosomal Protein S6 Kinases/metabolism , Blotting, Northern , Blotting, Western , Breast/enzymology , DNA, Complementary , Enzyme Activation , Female , Gene Expression Regulation, Neoplastic , Genes, erbB-2/genetics , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Prognosis , Ribosomal Protein S6 Kinases/genetics , Survival Analysis , Tumor Cells, Cultured , Up-Regulation
9.
Swiss Surg ; 6(3): 116-20, 2000.
Article in German | MEDLINE | ID: mdl-10894012

ABSTRACT

In view of introducing less invasive or selective axillary procedures for small breast cancers we investigated our own pT1 tumor patients. The incidence of pT1 carcinoma, the nodal involvement of pT1a, b and c, the axillary relapse and the overall survival were analyzed. From 1983 till 1997 185 consecutive patients have been treated for breast cancers with a diameter of < or = 20 mm. The survival data after Kaplan-Meier are based on a cohort of 117 patients with a median follow up of at least seven years. There were seven patients with a pT1a carcinoma, 30 with a pT1b and 148 with pT1c carcinoma. On an average 16 axillary lymph nodes were counted by the pathologists. The axillary involvement clearly depends on the size of the primary tumor: no nodal involvement in patients with pT1a carcinoma, 10% in patients with pT1b carcinoma and 30% in patients with pT1c carcinoma. Not one single axillary relapse was detected after this follow up time. The overall ten years survival for patients with pT1a was 100%, 91% for pT1b, but only 74% for pT1c carcinoma. Screening mammography is expected to detect more small breast cancers in pN0 stage. Risks and benefits of axillary dissection have to be carefully evaluated. Axillary involvement of small breast cancers is rare. Only a minority of patients will benefit from routine axillary lymphadenectomy, while the majority runs the risk of complications. The sentinel lymph node (SLN) procedure offers a selective approach to this dilemma.


Subject(s)
Breast Neoplasms/surgery , Lymph Node Excision/methods , Adult , Aged , Aged, 80 and over , Axilla/surgery , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Female , Follow-Up Studies , Humans , Lymph Nodes/pathology , Mammography , Middle Aged , Neoplasm Staging , Survival Rate
10.
Swiss Surg ; 6(3): 128-36, 2000.
Article in German | MEDLINE | ID: mdl-10894014

ABSTRACT

BACKGROUND: Axillary lymph node dissection (ALND) is an integral part in the therapy of breast cancer. Axillary lymph node involvement and tumour size are the most important prognostic factors. Restriction of ALND to level I and II (Berg) reduced high morbidity. The increasing proportion of patients with early breast cancer and negative axillary nodes led to a more selective method to avoid unnecessary ALND. The sentinel lymph node (SLN)--the first draining lymph node of a tumour--represents the status of the axilla. A negative SLN prevents from further completion ALND. PATIENTS AND METHODS: From 9/97 to 1/99 44 patients with invasive breast cancer underwent a prospective trial of lymphatic mapping with isosulfanblue and/or lymphoscintigraphy with 99m technetium-labelled human colloid. During the operation a hand-held gamma probe was used for detection. The SLN was removed selectively and examined by routine histopathology (H&E) and immunohistochemistry (IHC). ALND of level I and II was performed in all patients for correlation. RESULTS: The SLN were identified in 41 of 44 patients (93%). 2.4 SLN per patient were harvested, overall 17.6 axillary lymph nodes. Of the 41 patients, 21 patients had positive, 20 patients negative SLN. In the 20 patients with negative SLN only one patient (5%) had metastatic disease on complete dissection (negative predictive value of 95%). In 17 patients with positive axillary lymph nodes 16 were found to have positive SLN, only one SLN was negative (false negative rate of 5.9%). In two of 41 patients micrometastases were detected by IHC. Lymphoscintigraphy revealed drainage to the axilla and internal mammary nodes in two of 28 cases (7%). SUMMARY: Our validation study proves the reproducibility and reliability of the SLN procedure. A multidisciplinary approach is indispensable. The SLN procedure has the potency for becoming the selection criterion whether to perform an ALND or not. Multiple sections and IHC staining improve the detection rate of metastatic disease. Ongoing long time investigations will determine the impact on overall survival. Our own data are discussed in an extended review of the literature.


Subject(s)
Breast Neoplasms/pathology , Lymph Nodes/pathology , Adult , Aged , Aged, 80 and over , Axilla , Biopsy , Female , Humans , Lymph Node Excision , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Predictive Value of Tests , Prognosis
11.
Rofo ; 172(3): 287-94, 2000 Mar.
Article in German | MEDLINE | ID: mdl-10778462

ABSTRACT

Gastrointestinal stromal tumors (GIST) represent an extremely rare group of tumors, which are mostly of smooth muscle origin like leiomyomas, leiomyosarcomas and leiomyoblastomas. With the introduction of immunohistochemical analysis an epithelioid and an autonomic nerve variant can be distinguished. The purpose of this review is to demonstrate the image morphological appearance of these rare tumors together with the pathology based upon a retrospective analysis of five of our own cases since 1997. There are no pathognomonic imaging findings for characterizing a gastrointestinal stromal tumor; however, it should be included in the differential diagnosis if one or multiple large, round or oval, well-delineated gastrointestinal tumors occur in combination with central necrosis. Carney's syndrome is characterized by the syndromal association of a gastrointestinal stromal tumor (originally: gastric leiomyosarcoma) with an extra-adrenal paraganglioma and a pulmonary chondroma. In this rare syndrome, the radiological approach is important to diagnose or rule out the--simultaneous or consecutive--appearance of at least two of the three tumor entities (GIST, extra-adrenal paraganglioma, pulmonary chondroma).


Subject(s)
Chondrosarcoma/diagnostic imaging , Gastrointestinal Neoplasms/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Neoplasms, Multiple Primary/diagnostic imaging , Paraganglioma, Extra-Adrenal/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , Biopsy , Chondrosarcoma/diagnosis , Chondrosarcoma/pathology , Female , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/pathology , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/pathology , Paraganglioma, Extra-Adrenal/diagnosis , Paraganglioma, Extra-Adrenal/pathology , Rectal Neoplasms/diagnosis , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/pathology , Retroperitoneal Neoplasms/diagnosis , Retroperitoneal Neoplasms/diagnostic imaging , Retroperitoneal Neoplasms/pathology , Stomach Neoplasms/diagnosis , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Syndrome
12.
Cancer Res ; 59(14): 3475-9, 1999 Jul 15.
Article in English | MEDLINE | ID: mdl-10416613

ABSTRACT

The clinical behavior of invasive cervical carcinoma of clinical stage IB varies considerably in tumors presenting without regional lymph node metastases. The early identification of patients at higher risk for poor outcome may prove useful because these patients would benefit from aggressive adjuvant treatments. In this study, comparative genomic hybridization was applied to evaluate whether genomic aberrations have prognostic significance in cervical carcinoma. Genomic alterations were evaluated in 62 cervical carcinomas of clinical stage IB. DNA sequence losses were most prevalent at chromosomes 4q (53%), 3p (52%), 13q (45%), 4p (44%), Xq (44%), 5q (40%), 18q (37%), and 6q (35%). Several genomic alterations were associated with poor clinical outcome or metastasis. The total number of DNA aberrations/tumor (P < 0.02) and the number of DNA sequence losses/tumor (P < 0.04) were associated with disease-specific survival. 9p deletions were significantly more frequent in carcinomas with lymph node metastasis than in node-negative tumors (P < 0.03). Losses of chromosome 11p (P < 0.0001) and 18q (P < 0.01) were associated with poor prognosis in cervical carcinomas without lymph node metastasis. These data suggest that inactivation of tumor suppressor genes on chromosomes 9p, 11p, and 18q may play a role in the progression of cervical carcinoma.


Subject(s)
Carcinoma, Squamous Cell/genetics , Nucleic Acid Hybridization , Uterine Cervical Neoplasms/genetics , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Chromosome Aberrations , Chromosomes, Human/genetics , DNA, Neoplasm/genetics , Female , Follow-Up Studies , Humans , In Situ Hybridization, Fluorescence , Life Tables , Lymphatic Metastasis , Male , Prognosis , Proportional Hazards Models , Survival Analysis , Treatment Outcome , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathology
13.
Obstet Gynecol ; 94(1): 61-5, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10389719

ABSTRACT

OBJECTIVE: To compare two new transdermal, continuous, combined formulations and an oral regimen of hormone replacement therapy (HRT) with respect to endometrial hyperplasia, bleeding patterns, and climacteric symptoms in postmenopausal women. METHODS: This was a randomized, open, parallel-group trial during 1 year in 441 postmenopausal women who received either a 10-cm2 patch of 0.025 mg estradiol (E2) and 0.125 mg norethisterone acetate, a 20-cm2 patch of 0.05 mg E2 and 0.25 mg norethisterone acetate twice weekly, or tablets of 2 mg E2 and 1 mg norethisterone acetate once daily. The efficacy variables were frequency of endometrial hyperplasia after 1 year of treatment, number of bleeding and spotting days from the fourth to sixth treatment months, relief of climacteric symptoms, and tolerability. RESULTS: The frequency of endometrial hyperplasia was no more than 2% after 1 year of treatment in all groups. One case of simple hyperplasia was detected among the women treated with 10-cm2 patches and two among those treated with oral HRT. From the fourth to sixth treatment months, amenorrhea occurred in 73%, 47%, and 66% of the women in the 10-cm2, 20-cm2, and oral HRT groups, respectively. The 10-cm2 patches and oral treatment were associated with fewer bleeding days than were the 20-cm2 patches (P<.001). During the last 3 months of the treatment year, amenorrhea was found in 100 subjects (86%) for 10-cm2 patches, 61 (65%) for 20-cm2 patches, and in 85 (79%) for oral HRT. All treatments alleviated the climacteric symptoms to a comparable extent. CONCLUSION: In postmenopausal women, 10-cm2 patches relieved climacteric symptoms and prevented endometrial hyperplasia at least as effectively as oral HRT. Amenorrhea was induced early in a high percentage of women using 10-cm2 patches and oral HRT, and these therapies seemed to be convenient, effective, and safe for estrogen deficiency symptoms in postmenopausal women.


Subject(s)
Estradiol/administration & dosage , Estrogen Replacement Therapy , Norethindrone/analogs & derivatives , Administration, Cutaneous , Administration, Oral , Adult , Aged , Drug Therapy, Combination , Female , Humans , Middle Aged , Norethindrone/administration & dosage , Norethindrone Acetate
14.
Clin Nephrol ; 51(2): 67-72, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10069640

ABSTRACT

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAID) e.g. aspirin, indomethacin are reported in epidemiological and experimental studies to reduce the risk for colo-rectal cancer and potentially other malignant tumors. METHODS: We examined the effect of NSAIDs on tumor prevalence in abusers of mixed analgesics containing aspirin, phenacetine, caffeine or codein. 618 analgesic abusers who were autopsied between 1968-1983 were compared with a control group without evidence of analgesic abuse matched for sex, age and year autopsy was performed. RESULTS AND CONCLUSIONS: Abusers were found to have an overall risk of 0.40 fold of having developed a malignancy as compared with the controls. Excluding patients with urinary tract tumors which are increased in analgesic abusers the risk was further decreased to 0.28. No statistically significant effect was found for patients with prostate cancer. The results encourage prospective control studies in high risk patients.


Subject(s)
Analgesics/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Aspirin/administration & dosage , Neoplasms/prevention & control , Substance-Related Disorders , Aged , Female , Humans , Male , Odds Ratio , Risk Factors
15.
Cancer ; 83(7): 1376-83, 1998 Oct 01.
Article in English | MEDLINE | ID: mdl-9762939

ABSTRACT

BACKGROUND: A recently cloned novel p150 protein was found to be overexpressed in human breast carcinoma. To the authors' knowledge, no data on p150 expression in any other human tumors have been published previously. METHODS: To investigate whether the expression of p150 correlated with the clinicopathologic stages of cervical neoplasms or the prognoses of patients with these neoplasms, the authors conducted an immunohistochemical study of archival formalin fixed, paraffin embedded specimens. Seventy-two precancerous lesions (CIN), 75 clinical Stage IB invasive squamous carcinomas, and 20 samples of normal squamous epithelia were included. In addition to p150, the Ki-67 labeling index was assessed as a proliferation parameter. The presence of human papillomavirus was analyzed by in situ DNA hybridization. RESULTS: A significant association of p150 with the grade of atypia in cervical neoplasms was demonstrated. The highest expression of p150 was observed in low grade CIN, with subsequently decreasing expression in high grade CIN and invasive carcinoma. For patients with invasive carcinoma, p150 was significantly correlated with clinical outcome. Patients with high expression of p150 had a better prognosis than those with low p150. Those with regional lymph node metastasis and significant p150 expression had longer relapse free survival than those with insignificant p150 expression. Women whose carcinomas demonstrated vascular space invasion or high microvessel density survived longer when p150 was clearly expressed. p150 behaves as a potential tumor marker during early cervical carcinoma development and is later turned off as cells proceed to more advanced stages of their malignant phenotypes. CONCLUSIONS: p150 is a molecular parameter that might become useful in predicting disease progression and determining the prognoses of patients with invasive cervical carcinoma.


Subject(s)
Biomarkers, Tumor/analysis , Cytoskeletal Proteins/analysis , Uterine Cervical Neoplasms/mortality , Carcinoma in Situ/chemistry , Carcinoma in Situ/mortality , Carcinoma, Squamous Cell/chemistry , Carcinoma, Squamous Cell/mortality , Disease-Free Survival , Eukaryotic Initiation Factor-3 , Female , Humans , Immunohistochemistry , Ki-67 Antigen/analysis , Lymphatic Metastasis , Neoplasm Invasiveness , Papillomaviridae/isolation & purification , Prognosis , Uterine Cervical Neoplasms/chemistry
16.
Anticancer Res ; 18(4B): 2811-4, 1998.
Article in English | MEDLINE | ID: mdl-9713466

ABSTRACT

A one-page family history questionnaire was validated in two European areas covered by population-based cancer registries. Information on malignant tumor occurrence in first degree relatives was collected from 193 cancer patients in Trieste, Italy and from 64 in Basel, Switzerland. They were then compared with the corresponding data stored in the registries' files. The sensitivity of the questionnaire was 85% (Trieste) and 74% (Basel), the specificity was 97% in both studies and the overall accuracy 95% (Trieste) and 94% (Basel). The questionnaire is recommended for use in different geographical areas covered by population based registries for comparative analyses of cancer related family histories.


Subject(s)
Family Health , Neoplasms/epidemiology , Surveys and Questionnaires , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Pilot Projects , Reproducibility of Results , Sensitivity and Specificity
17.
Nat Med ; 4(7): 844-7, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9662379

ABSTRACT

Many genes and signalling pathways controlling cell proliferation, death and differentiation, as well as genomic integrity, are involved in cancer development. New techniques, such as serial analysis of gene expression and cDNA microarrays, have enabled measurement of the expression of thousands of genes in a single experiment, revealing many new, potentially important cancer genes. These genome screening tools can comprehensively survey one tumor at a time; however, analysis of hundreds of specimens from patients in different stages of disease is needed to establish the diagnostic, prognostic and therapeutic importance of each of the emerging cancer gene candidates. Here we have developed an array-based high-throughput technique that facilitates gene expression and copy number surveys of very large numbers of tumors. As many as 1000 cylindrical tissue biopsies from individual tumors can be distributed in a single tumor tissue microarray. Sections of the microarray provide targets for parallel in situ detection of DNA, RNA and protein targets in each specimen on the array, and consecutive sections allow the rapid analysis of hundreds of molecular markers in the same set of specimens. Our detection of six gene amplifications as well as p53 and estrogen receptor expression in breast cancer demonstrates the power of this technique for defining new subgroups of tumors.


Subject(s)
Breast Neoplasms/genetics , Genetic Techniques , Animals , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cyclin D1/genetics , Cyclin D1/metabolism , Female , Humans , Immunoenzyme Techniques , In Situ Hybridization, Fluorescence , Mice , Oncogene Proteins v-myb , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , Rabbits , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism , Retroviridae Proteins, Oncogenic/genetics , Retroviridae Proteins, Oncogenic/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
18.
Schweiz Med Wochenschr ; 128(21): 811-6, 1998 May 23.
Article in German | MEDLINE | ID: mdl-9642747

ABSTRACT

Advanced Breast Biopsy Instrumentation (ABBI) allows radiologically guided stereotactic excision of non-palpable radiodense lesions with high accuracy. Tissue cylinders of 5, 10, 15 or 20 mm diameter and of variable lengths can be removed very accurately under local anaesthesia and on an outpatient basis. Thirty-six patients with suspicious clusters of microcalcifications (n = 29) and with round lesions (n = 7) of the breast were qualified for ABBI. We were able to perform the excisional biopsy in a total of 34 patients. The breast of one woman was too small to safely fit into the system and in another woman the lesion could not be visualized by the system. In 2/34 cases (6%), the excision was imprecise due to slight dislocation of the breast parenchyma by the advancing cylinder knife. In one case (3%), ABBI missed the target within a dense mastopathic breast. In all cases the excisions were well tolerated. No wound complications occurred and the cosmetic result was excellent. Histology revealed 28 benign (82%) and 6 malignant (18%) lesions. Among the 27 small microcalcifications there were 3 invasive carcinomas, 3 ductal carcinomas in situ (DCIS), 1 lobular hyperplasia, 14 mastopathies, 1 fibroadenoma, 1 duct papilloma and 4 calcifications in scars. Four of the 7 round-shaped lesions were found to be fibroadenomas, 1 lobular hyperplasia, and 2 mastopathies. With the ABBI system, non-palpable breast lesions can be precisely localized and excised.


Subject(s)
Biopsy/instrumentation , Breast Neoplasms/pathology , Mammography/instrumentation , Precancerous Conditions/pathology , Adult , Aged , Breast/pathology , Breast Neoplasms/diagnostic imaging , Calcinosis/diagnostic imaging , Calcinosis/pathology , Diagnosis, Differential , Equipment Design , Female , Fibrocystic Breast Disease/diagnostic imaging , Fibrocystic Breast Disease/pathology , Humans , Middle Aged , Precancerous Conditions/diagnostic imaging , Sensitivity and Specificity
19.
Gynecol Oncol ; 68(3): 293-6, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9570983

ABSTRACT

A patient is described who was treated with tamoxifen for breast cancer and developed an androgen-producing ovarian tumor of low malignant potential, which itself is a rare condition. Clinically overt virilism was leading to the diagnosis and promptly improved after surgical removal of the tumor. A causal relationship between tamoxifen use and the tumor is discussed on the basis of the known tumor-inducing potential of tamoxifen.


Subject(s)
Antineoplastic Agents, Hormonal/adverse effects , Breast Neoplasms/drug therapy , Neoplasms, Second Primary/chemically induced , Ovarian Neoplasms/chemically induced , Ovarian Neoplasms/complications , Tamoxifen/adverse effects , Virilism/etiology , Androgens/biosynthesis , Androgens/blood , Antineoplastic Agents, Hormonal/therapeutic use , Epithelium/pathology , Female , Humans , Middle Aged , Neoplasms, Second Primary/complications , Neoplasms, Second Primary/pathology , Ovarian Neoplasms/pathology , Tamoxifen/therapeutic use , Virilism/blood
20.
Recent Results Cancer Res ; 152: 180-9, 1998.
Article in English | MEDLINE | ID: mdl-9928557

ABSTRACT

Nonpalpable, mammographically detected breast cancers are on the increase. The percentage of patients with histologically involved nodes is therefore decreasing. Axillary clearance aims at reducing the probability of later clinical involvement of the axilla and at establishing a sound basis for adjuvant treatment planning. Minimally invasive techniques have been applied to a growing number of surgical procedures now including exploration of the axilla. The technique used and results achieved in a series of 50 consecutive patients treated by liposuction and axilloscopy by one single surgeon, including all the patients from the very first attempt, are presented here. Patients were excluded with palpable lymph nodes or a primary tumor in the direct vicinity of the axilla that could be injured by the liposuction canula. The average number of lymph nodes removed was 13.4. Thirty-four percent of patients had involved nodes. The mean number of involved nodes in these patients was 3.1. After a median follow-up time of only 15 months no axillary recurrences or trocar site metastases have been found in the first 40 patients. Using a self-assessment questionnaire, the patients rate this technique as excellent. There was no lymphedema. The cosmetic result is certainly better than after conventional axillary clearance. Great experience of laparoscopic surgery and an excellent knowledge of the axillary anatomy are prerequisites for the practice of axilloscopic treatment of the axilla. The working space within the axilla is small and a number of structures need absolutely to be preserved. A longer follow-up period than the one so far achieved in this series or any other in the literature to date is necessary before this technique can be generally recommended.


Subject(s)
Axilla/surgery , Endoscopy , Lymph Node Excision/methods , Female , Humans , Lymphatic Metastasis , Middle Aged , Patient Selection
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