Pathway to the piezoelectronic transduction logic device.

The piezoelectronic transistor (PET) has been proposed as a transduction device not subject to the voltage limits of field-effect transistors. The PET transduces voltage to stress, activating a facile insulator-metal transition, thereby achieving multigigahertz switching speeds, as predicted by modeling, at lower power than the comparable generation field effect transistor (FET). Here, the fabrication and measurement of the first physical PET devices are reported, showing both on/off switching and cycling. The results demonstrate the realization of a stress-based transduction principle, representing the early steps on a developmental pathway to PET technology with potential to contribute to the IT industry.

Schottky-to-Ohmic crossover in carbon nanotube transistor contacts.

For carbon nanotube transistors, as for graphene, the electrical contacts are a key factor limiting device performance. We calculate the device characteristics as a function of nanotube diameter and metal work function. Although the on-state current varies continuously, the transfer characteristics reveal a relatively abrupt crossover from Schottky to Ohmic contacts. We find that typical high-performance devices fall surprisingly close to the crossover. Therefore, tunneling plays an important role even in this regime, so that current fails to saturate with gate voltage as was expected due to "source exhaustion."

Glycosyltransferase expression in human colonic tissue examined by oligonucleotide arrays.

For an understanding of tumor-related alterations of the complex carbohydrate pattern of carcinomas, it is indispensable to monitor the expression profile of the various glycosyltransferases. The objective of this contribution was to perform an evaluation of the usefulness and the limits of the microarray approach for the identification of enzymes responsible for carbohydrate synthesis with differential expression in carcinomas. Expression profiles of colonic carcinomas were studied by oligonucleotide arrays using a novel strategy: colonic tissue of healthy individuals was compared with early staged colonic carcinomas; 'pure' cell populations were obtained by laser microdissection; RNA samples for hybridization with the oligonucleotide arrays were prepared by in vitro transcription without additional amplification. Expression of 39 glycosyltransferases and of 10 sulfotransferases in colonic tissues was analyzed by Affymetrix GeneChip technology. GeneChip analysis proved the high expression level of ST6Gal-I, beta4Gal-TI, II and III, GalNacT-1, FT-III and showed that ST3Gal-IV was the most abundantly expressed enzyme in healthy tissue. The strong overexpression of FT-VI in healthy tissue has not been described so far, as well as the upregulation of FT-VIII and downregulation of GnT-I in carcinoma tissue. Quantitative RT-PCR confirmed that FT-VI expression was significantly enhanced in healthy tissue. On the other hand, GeneChip analysis failed to detect any expression of GnT-III and GnT-V as well as of ST3Gal-I and ST3Gal-II, although these sequences could be amplified from the samples used for microarray analysis. According to our restricted analysis of only those 39 glycosyltransferases present on the GeneChip U95A, alterations of sialyltransferases ST6Gal-I, ST3Gal-IV, of fucosyltransferases FT-VI, FT-III, and probably FT-VIII, of GalNacT-I, and of beta4GalT-II seem to be of relevance for the aberrant biosynthesis of membrane-bound carbohydrates during colonic carcinogenesis and metastasis.

Titer determination of Ad5 in blood: a cautionary note.

Recombinant adenoviruses are presently the most efficient in vivo gene transfer system available. Targeting single organs or large tumors by adenoviral vectors requires an intravascular route of application. During the first pass of viral particles through the vascular bed of the target tissue, virus uptake is not quantitative and indefinite amounts of particles leak into circulation. To determine the amount of leaking particles and to calculate organ-specific uptake (in-/outflow ratio), it is necessary to titrate virus particles directly in blood. In preclinical and clinical trials titration is currently mostly done with blood plasma instead of full blood. However, this technique provides valid results only as long as there is no affinity between adenovirus particles and erythrocytes. In this study we demonstrate that Ad5 particles, as mostly employed for gene therapy, have a strong affinity to human erythrocytes. At 60 min after coincubation of human erythrocytes and Ad5 particles, more than 98% of the particles are attached to the surface of erythrocytes. Therefore, ignoring the amount of red cell bound particles by performing titration in plasma leads to severe miscalculation of organ-specific transfer rates or virus circulation half-life. The biological impact of an increased affinity between virus particles and erythrocytes will be discussed.

Mid-IR microspectroscopic imaging of breast tumor tissue sections.

IR microspectroscopic imaging is a relatively new approach for the examination of tissue sections. In contrast to standard light microscopy based procedures, the IR approach requires neither sample staining nor fixation. The IR spectra of breast tumor tissue sections are obtained via a microscope equipped with a focal plane array detector. This enabled the simultaneous collection of individual mid-IR spectra from thousands of different sample positions with a spatial resolution near the diffraction limit. The analysis of the IR data reveals a high sensitivity of the IR approach toward changes in tissue biochemistry and variations in breast tissue architecture. Moreover, the data demonstrate the need for collecting spectra with high spatial resolution at the level of individual cells. This minimizes problems associated with tissue microheterogeneity and is an essential prerequisite for future studies aimed at developing IR microspectroscopic imaging as a complement to present diagnostic tools for breast cancer.

Detailed deletion mapping in sporadic breast cancer at chromosomal region 17p13 distal to the TP53 gene: association with clinicopathological parameters.

Chromosome 17p is among the most frequently deleted regions in a variety of human malignancies including breast cancer. This study has further refined the localization of a putative tumour suppressor gene (TSG) at 17p13 distal to the TP53 gene in breast carcinomas. It was found that 73% (37 of 51) of the breast tumours exhibited loss of heterozygosity (LOH) at one or more loci at 17p13. The allelic loss patterns of these tumours suggest the presence of at least seven commonly deleted regions on 17p13. The three most frequently deleted regions were mapped at chromosomal location 17p13.3-17p13.2 between the markers D17S831 and D17S1845 (56% LOH), at 17p13.1 between D17S1810 and D17S1832 (53% LOH), and at 17p13.1 between D17S938 and TP53 (55% LOH). A significant correlation was found between loss at 17p13 and tumour grade, size, proliferative activity, and oestrogen receptor (ER) status. Losses at 17p13 were seen more frequently in large and poorly differentiated tumours with high proliferative activity. These data support and extend previous reports on the presence of a putative TSG(s) at chromosomal region 17p13 distal to the TP53 gene and show that different subsets of LOH are associated with more aggressive tumour behaviour.

Overexpression of sialyltransferase CMP-sialic acid:Galbeta1,3GalNAc-R alpha6-Sialyltransferase is related to poor patient survival in human colorectal carcinomas.

Thomsen-Friedenreich (TF)-related blood group antigens, such as TF, Tn, and their sialylated variants, belong to a family of tumor-associated carbohydrates. The aim of the present study was to examine tumor-associated alterations of glycosyltransferases involved in the biosynthesis of the TF glycotope in colorectal carcinomas. To this end, glycosyltransferase expression was examined in 40 cases of colorectal carcinoma specimens classified according to the WHO/Union International Contre Cancer guidelines and in "normal" mucosa of the same patients. Occurrence of TF glycotope was examined by immunohistochemistry with the monoclonal antibody A78-G/A7. Expression of sialyltransferases CMP-sialic acid:Galbeta1,3GalNAc-R alpha3-sialyltransferase I and II (ST3Gal-I and ST3Gal-II) and CMP-sialic acid:Galbeta1,3GalNAc-R alpha6-sialyltransferase (ST6GalNAc-II) and of core 2 beta1,6-N-acetylglucosaminyltransferase was determined by reverse transcription-PCR in the same cryostat sections used for immunohistochemistry. Additionally, alpha2,3-sialyltransferase enzyme activity was studied in each of these tissues. The TF glycotope was detected in 7% of the normal mucosa, but in 57% of the carcinoma samples. Expression of alpha2,3-sialyltransferases ST3Gal-I, ST3Gal-II, and enzyme activity of alpha2,3-sialyltransferase was significantly increased (P < 0.001) in carcinoma specimens compared with normal mucosa. ST3Gal-I mRNA expression was significantly increased (P = 0.05) in cases showing invasion of lymph vessels. Expression of ST6GalNAc-II was significantly increased (P = 0.04) in cases with metastases to lymph nodes along the vascular trunk. Moreover, ST6GalNAc-II expression provides an prognostic factor for patient survival (log rank, P = 0.02). In an attempt to study the functional relevance of the glycosyltransferases for TF biosynthesis, SW480 colorectal cells were transfected with each of the enzymes, and cell surface expression of the TF glycotope was examined by flow cytometry. The presence of TF was not altered by transfection of the cells with either sialyltransferase ST3Gal-I or ST3Gal-II. However, successful transfection with core 2 beta1,6-N-acetylglucosaminyltransferase led to reduced expression of TF. In contrast, increased cell surface expression of TF was found after ST6GalNAc-II transfection. Thus, expression of TF on the cell surface of SW480 colorectal carcinoma cells depends on the ratio of core 2 beta1,6-N-acetylglucosaminyltransferase and ST6GalNAc-II. Earlier immunohistological studies demonstrated that TF is a prognostic factor for patient survival. Our results suggest that sialyltransferase ST6GalNAc-II is of crucial relevance for the prognostic significance of TF.

Prognostic significance of activated CD8(+) T cell infiltrations within esophageal carcinomas.

The purpose of this study was to explore whether there is a linkage between the infiltration of CD8(+) T cells and the risk of death from esophageal cancer. Cases of 70 consecutive patients in whom esophageal squamous cell carcinomas ( n = 33) or adenocarcinomas (n = 37) were R0-resected between 1993 and 1999 were reviewed. The presence of activated CD8(+) T cells was evaluated by quantitative real-time PCR and immunohistochemistry and compared to clinical and pathological stages. The primary end point analyzed was overall survival, and a multivariate analysis was performed to distinguish any factors conferring an improved survivorship. Intratumoral (i.t.) CD8(+) T cells accumulating within the epithelial complexes were detected in 11 of all (16%) cases: in 9 of 25 (36%) patients with Union Internationale Contrele Cancer stage I or II versus 2 of 45 (4%) patients with Union Internationale Contrele Cancer stage III or IV (P = 0.001). Intratumoral CD8(+) T cell infiltrations showed proliferative activity and also IFN-gamma secretion. The presence of i.t. CD8(+) T cell infiltration more than peritumoral infiltration was associated with a good prognosis in both squamous cell and adenocarcinomas. Multivariate analysis showed that i.t. CD8(+) T cell infiltration was an independent prognostic factor (hazard ratio, 0.5; P = 0.0004) indicating favorable outcome. In conclusion, the presence of CD8(+) T cell infiltration in esophageal carcinomas is a favorable prognostic factor that should have diagnostic and therapeutic implications.

Protoporphyrin IX occurs naturally in colorectal cancers and their metastases.

Colorectal cancers exhibit a red fluorescence. The nature of the responsible fluorophore and its eventual diagnostic potential were investigated. Thirty-three consecutive colorectal resection specimen, 32 of which with histologically confirmed cancer, and a total of 1053 palpable mesenteric nodes were fluorimetrically characterized ex vivo. Furthermore, frozen material from 28 patients was analyzed, selected for the availability of primary tumor material and metastatic tissue, e.g., lymphatic and liver metastases from the same patient. Biochemical characterization was carried out through chemical extraction and reversed phase high-performance liquid chromatography. The fluorescence spectra of tissues, tissue extracts, and standard solutions of porphyrins were determined using a pulsed solid-state laser system for excitation and an imaging polychromator, together with an intensified CCD camera for time-delayed observation. Protoporphyrin IX (PpIX) was identified as the predominant fluorophore in primary tumors and their metastases. The fluorophore occurred in the absence of necrosis and in sterile locations. In untreated cases (n = 24), PpIX fluorescence discriminates metastatically involved lymph nodes from all other palpable nodes with a sensitivity of 62% at a specificity of 78% (P < 0.0001). After neoadjuvant treatment of rectal cancer, the PpIX fluorescence level of the primary tumors was reduced and a discrimination of lymph nodes based on PpIX-fluorescence was impossible. We conclude that colorectal cancer metastases accumulate diagnostic levels of endogenous PpIX as a result of a tumor-specific metabolic alteration.

Accuracy of endorectal ultrasound after preoperative radiochemotherapy in locally advanced rectal cancer.

OBJECTIVES: Factors limiting the accuracy of endorectal ultrasound in staging, locally advanced primary rectal cancer after preoperative neoadjuvant radiochemotherapy (RCT) were evaluated. METHODS: Patients (n = 84) with initial locally advanced rectal cancer (uT3/uT4) undergoing R0 resection were investigated after preoperative treatment that combined radiotherapy up to 45 Gy with two cycles of chemotherapy (5-FU and leucovorin on d 1-5 and 22-28). At 4 to 6 weeks after completion of RCT and before tumor resection, preoperative endoluminal ultrasound was performed. RESULTS: The accuracy to predict the depth of tumor infiltration (T-category) was found to correlate with downstaging. The T-category was correctly staged before surgery in 15 of the 51 responders (29%) and in 27 of 33 nonresponders (82%), whereas misinterpretation occurred in 36 of the responders (71%) and in 6 of the nonresponders (18%) (p < 0.001). Neither tumor distance from anal verge nor tumor location correlated with the staging accuracy. Lymph node involvement was correctly assessed in 48 patients (57%). Wall invasion was correctly ascertained in 42 patients (50%), with under estimation in 11 patients (13%) and overestimation in 31 patients (37%). CONCLUSIONS: After radiochemotherapy, endosonography does not provide a satisfactory accuracy for preoperative staging of rectal cancer. New interpretation and diagnostic criteria are needed for the prediction of treatment response.

Immunohistological analysis of E-cadherin, alpha-, beta- and gamma-catenin expression in colorectal cancer: implications for cell adhesion and signaling.

Intercellular adhesion mediated by the E-cadherin/catenin complex is a prerequisite for epithelial integrity and differentiation. In carcinomas, E-cadherin function is frequently disturbed, and has been suggested to increase invasion and metastasis of tumour cells. beta-catenin has also been implicated in signaling pathways essential for tumour formation. We analysed the E-cadherin/catenin adhesion system of colorectal tumours at different clinical stages. In primary carcinomas (n = 91), there was a frequent reduction in E-cadherin (44%) and alpha-catenin expression (36%). In contrast, beta-catenin and gamma-catenin expression were seldom reduced (4% and 15%, respectively). Similar expression patterns were observed in liver metastases from unrelated colorectal tumours (n = 27). There was a significant relationship between loss of E-cadherin and alpha-catenin expression and poorly differentiated (G3-4) tumours. Our results suggest that reduction of E-cadherin/alpha-catenin expression is a frequent event in primary and metastatic colorectal carcinomas. Furthermore, beta-catenin expression remains normal in colorectal cancer, suggesting the essential role of beta-catenin in signaling pathways.

GLI gene expression in bone and soft tissue sarcomas of adult patients correlates with tumor grade.

The GLI gene encodes a transcription factor harboring five zinc finger motifs that bind to DNA in a sequence-specific manner. The gene was originally identified because of its amplification in a human glioblastoma, and previous studies have shown it to be amplified in a significant proportion of mesenchymal tumors, such as childhood sarcomas. Here we evaluate GLI gene expression in bone and soft tissue sarcomas of adult patients. Samples from 40 patients (37 sarcomas and 3 benign mesenchymal tumors) and samples of 15 normal mesenchymal tissues were examined for GLI gene amplification and expression by Southern hybridization, reverse transcription-PCR of tissue RNA, and immunohistochemistry, using a new polyclonal GLI antibody developed against an epitope outside of the zinc finger region. In contrast to childhood sarcomas, amplification of the GLI gene was not observed in sarcomas of adult patients. Although GLI gene expression in sarcomas was significantly higher than that in normal mesenchymal tissues (P < 0.0001), the levels were very variable. Attempts to correlate the expression data with different pathophysiological parameters only showed a significant relationship to tumor grade. Based on these data, increased levels of GLI gene expression may be indicative of the aggressiveness of the tumor.

Transendoscopic ultrasound of esophageal and gastric cancer using miniaturized ultrasound catheter probes.

BACKGROUND: The aim of this study was to investigate the value of miniaturized ultrasound catheter probes (miniprobes) for preoperative staging of esophageal and gastric cancer. METHODS: Fifty-one patients with esophageal (n = 21) and gastric cancer (n = 30) underwent endoscopic ultrasound (EUS). All examinations were carried out using mechanical miniprobes (diameter 6F, 12.5 MHz) that were introduced through the instrument channel of the endoscope. RESULTS: EUS with miniprobes was successfully performed in all patients, although stenotic tumors, which could not be traversed with the endoscope, were found in 6 of 21 patients (29%) with esophageal cancer. Miniprobe scanning provided high-resolution images of the gastrointestinal tract. The overall accuracy in the assessment of tumor infiltration depth for esophageal and gastric cancer was 90% and 82%, respectively. However, the value of miniprobe scanning in the assessment of advanced tumors was limited by the imaging depth of the probe (approximately 3 cm). Lymph node involvement was accurately diagnosed in 78% of the patients with esophageal cancer (sensitivity 75%, specificity 80%) and in 80% of the patients with gastric cancer (sensitivity 73%, specificity 89%). CONCLUSIONS: EUS with miniprobes can be performed as single-step procedure during diagnostic endoscopy. The 12.5 MHz transducer provides high-resolution imaging and enables accurate staging of tumors with limited infiltration depth.

Transesophageal biopsy of mediastinal and pulmonary tumors by means of endoscopic ultrasound guidance.

OBJECTIVE: The aim of this study was to investigate the value of endoscopic ultrasound-guided biopsy for the diagnosis of thoracic lesions. METHODS: Transesophageal ultrasound-guided biopsy was performed in 29 patients with mediastinal (n = 25) or pulmonary tumors (n = 4). A flexible echoendoscope with a 7.5 MHz curved array transducer (Pentax FG 32 UA, Hamburg, Germany) and a biopsy device with a fine needle (diameter 0.8 mm) were used for all examinations. Three patients were excluded from the analysis of the data because a definite diagnosis based on surgery or follow-up was not available. RESULTS: Real-time visualization of the biopsy procedure with endoscopic ultrasound enabled accurate tissue sampling even of small mediastinal lesions with a diameter of less than 1 cm. Diagnostic material was obtained in 23 of the 26 patients (88%). In 3 cases (12%) non-representative biopsy material was found in the specimen. The sensitivity and specificity of transesophageal biopsy in the diagnosis of malignancy were 89% and 83%, respectively. Histologic analysis of the biopsy specimens established malignancy in 17 of 23 patients, whereas benign lesions were diagnosed in 6 patients. Endoscopic ultrasound-guided biopsy confirmed the diagnosis suggested by conventional diagnostic methods in 15 of 23 patients (65%), whereas an unsuspected diagnosis was disclosed in 8 patients (35%). The results of the biopsy had considerable impact on the therapeutic strategy. None of the patients had complications related to the procedure. CONCLUSIONS: Endoscopic ultrasound-guided biopsy provides a new minimally invasive approach to the biopsy of lesions in the posterior mediastinum and may complement surgical staging procedures.

[Axillary node removal in clinical node-negative breast carcinoma. Can its indication be individualized by "sentinel node" detection?]. / Axillaausräumung bei klinisch nodal-negativem Mammakarzinom. Kann die Indikation durch "sentinel node"-Nachweis individualisiert werden?

BACKGROUND AND OBJECTIVE: The status of the axillary lymph node(s) is an important prognostic factor in breast cancer and thus decisive in the indication for adjuvant treatment. This study investigated the extent to which examination of the sentinel node (SN) can individualize the need for axillary resection and the diagnosis of lymph nodes be optimized. PATIENTS AND METHODS: 96 consecutive patients with breast cancer were studied (94 women, 2 men; mean age 59 [36-84] years) in whom no lymph node enlargement had been diagnosed clinically. After preoperative lymph-drainage scintigraphy with 99mTc Nanocoll combined with intraoperative scintillation probe detection the SN node was identified in 77 of the 96 patients and was removed. Subsequently the axillary lymph nodes in level I and II were removed by a standard technique and all removed lymph nodes and material then compared histologically. RESULTS: In nine of 77 patients with identifiable SN it was the only lymph node with metastasis. In 18 patients both the SN and other axillary lymph nodes were infiltrated. The SN and other axillary lymph nodes were free of metastases in 44 patients. In six patients the SN was not representative, since it was free of tumour, but other axillary nodes were not. Identification of a SN and prognostication of lymphogenic axillary metastases depended on tumour size. Among T3 and T4 tumours, ten of 16 had a verifiable SN, but in six of them it was not representative for axillary metastasization. But in 62 of 73 patients with tumours up to 5 cm in diameter without involvement of skin or chest wall (T1 and T2, respectively) a SN could be identified that was not representative for axillary metastases in only two cases. CONCLUSIONS: SN resection in breast cancer makes it possible to individualize axillary node resection as part of primary treatment. Specific histological examination of serial sections and immunohistological testing may possibly increase the accuracy of histological diagnosis.

Tumor oxygenation correlates with molecular growth determinants in breast cancer.

UNLABELLED: Hypoxic tumor cells may represent a fraction of cells that are not susceptible to radiation or chemotherapy. Intratumoral oxygen partial pressure (pO2) is the result of oxygen delivery and consumption. Cell proliferation is one factor to effect oxygen consumption and we therefore studied the correlation between tumor pO2 and histological parameters. PATIENTS AND METHODS: In 36 women and one man (age range 29-80 years) with suspected breast cancer. Before tumor resection, intralesional pO2 was determined with a polarographic needle electrode. Under ultrasound control, 200 tumor measurements were obtained; Hb levels, Hk, arterial blood gas parameters, and tissue temperature were determined. The median of pO2 values and the percentage of hypoxic areas (pO2 < 10 mmHg) were calculated and correlated with the histological type, grading, ER, PR, and the expression of Ki-67, p53, EGFR, pS2, and c-erb-B2. RESULTS: The overall median pO2 was 44 mmHg, and 1024 measurements (13.8%) represented hypoxic areas. Ductal and lobular invasive cancers showed median pO2 of 41 mmHg. The mean pO2 of G1 tumors was 59 mmHg and the hypoxic fraction 8%, in contrast to G2 tumors with 43 mmHg and 17%, and G3 tumors with 36 mmHg and 20.4% (p < 0.01). We observed a correlation with tumor size and an increased rate of hypoxic areas in T3-4 lesions (p < 0.02). Also tumors with negative nodes or positive ER had significantly higher pO2 values, as did tumors with an overexpression of c-erb-B2, p53, and cathepsin D. CONCLUSION: Oxygenation of human breast cancers can safely be measured in patients prior to surgical therapy. pO2 values correlate both with prognostic markers examined histologically and with molecular growth factors. As the efficacy of preoperative or adjuvant treatment in individuals may depend on oxygen partial pressure, efforts to manipulate tumor pO2 for therapeutic purpose could be promising.

Endosonography-guided biopsy of mediastinal and pancreatic tumors.

BACKGROUND: Although endoscopic ultrasound (EUS) allows sensitive imaging of the upper gastrointestinal (GI) tract, it remains difficult to differentiate between benign and malignant lesions on the basis of ultrasound morphology. The purpose of this study was to determine the value of EUS-guided biopsy for the diagnosis of submucosal and extraluminal tumors. METHODS: EUS-guided biopsy was carried out in 50 patients with upper GI-tract lesions. All patients were examined using a flexible echoendoscope with a 5/7.5 MHz curved array transducer. A specially designed biopsy device (type Vilmann) with a fine needle (diameter 0.8 mm) was used for EUS-guided biopsy. RESULTS: EUS-guided biopsy was performed for evaluation of mediastinal lesions (n = 15), pancreatic tumors (n = 26) and submucosal (n = 5) or stenotic tumors of the esophagus (n = 4). Fine-needle aspiration yielded diagnostic tissue samples in 44 of 50 patients (88%). Histology demonstrated benign lesions in 20 of 44 patients and malignant tumors in the other 24 patients. EUS-guided biopsy failed in only six patients (12%): in four patients it was impossible to advance the needle into very hard pancreatic tumors; non-representative biopsy material was obtained in two further cases. The results of EUS-guided biopsy were validated by surgery (n = 21), autopsy (n = 3) or clinical follow-up (n = 20). After a mean follow-up of 16 months there is no evidence of malignancy in any of the patients with benign histology. The sensitivity and specificity of EUS-guided biopsy in the diagnosis of malignancy were 88% and 100%, respectively. None of the patients experienced complications related to endosonographic biopsy. CONCLUSIONS: EUS-guided biopsy with the Vilmann needle device is a safe and accurate method for tissue sampling of extraluminal lesions. This technique considerably improves the diagnostic value of endosonography.

[Sentinel lymph node detection in patients with breast carcinoma]. / Die Sentinel Lymphknoten-Detektion bei Patienten mit Mammakarzinom.

Sentinel node detection enables the definition of the most relevant draining lymph node of a tumor. We analysed 123 patients with breast cancer according to this method. A preoperative lymphoscintigraphy was performed 17 hours after a peritumoral application of 0.5 ml 99mTC-Nanokoll. The sentinel node was identified by means of a gammaprobe in 75 of 89 patients with pT1- and pT2-tumors and in 11 of 17 patients with pT3-4 tumors respectively. The results of histological investigation of the sentinel node in comparison to all other axillary nodes following dissection were correlated. In the pT1-2 group the accuracy of correlative findings was rather high (96%). In patients with pT3- and pT4-tumors the lymph node status was predictable only in 7 patients. Therefore sentinel node biopsy may serve as a tool for individualization of axillary dissection especially in pT1-2 breast cancer patients.