Purpose: Detection of sentinel lymph node (SLN) metastasis in breast cancer patients has conventionally been determined by intraoperative histopathologic examination of frozen sections followed by definitive postoperative examination of permanent sections. The purpose of this study is to develop a more efficient method for intraoperative detection of lymph node metastasis. Experimental Design: Cutoff values to distinguish macrometastasis, micrometastasis, and nonmetastasis were determined by measuring cytokeratin 19 (CK19) mRNA in histopathologically positive and negative lymph nodes using one-step nucleic acid amplification (OSNA). In an intraoperative clinical study involving six facilities, 325 lymph nodes (101 patients), including 81 SLNs, were divided into four blocks. Alternate blocks were used for the OSNA assay with CK19 mRNA, and the remaining blocks were used for H&E and CK19 immunohistochemistryb ased three-level histopathologic examination. The results from the two methods were then compared. Results: We established CK19 mRNA cutoff values of 2.5 Â 10 2 and 5 Â 10 3 copies/AL. In the clinical study, an overall concordance rate between the OSNA assay and the three-level histopathology was 98.2 %. Similar results were obtained with 81 SLNs. The OSNA assay discriminated macrometastasis from micrometastasis. No false positive was observed in the OSNA assay of 144 histopathologically negative lymph nodes from pN0 patients, indicating an extremely low false positive for the OSNA assay. Conclusion: The OSNA assay of half of a lymph node provided results similar to those of three-level histopathology. Clinical results indicate that the OSNA assay provides a useful intraoperative detection method of lymph node metastasis in breast cancer patients.Sentinel lymph node (SLN) biopsy has recently become a standard surgical procedure in the treatment of breast cancer patients (1 -10). This procedure can predict metastasis to the regional lymph nodes with high accuracy and avoids unnecessary removal of axillary lymph nodes and subsequent morbidity associated with axially clearance in node negative breast cancer patients.SLN metastasis is generally detected by conventional means including the intraoperative H&E-based histopathologic examination of frozen section(s) or cytologic observation of touchimprints, followed by definitive postoperative histopathologic examination of permanent sections (2, 7 -9). However, the sensitivity of these intraoperative methods is not high. Many investigators have reported that the intraoperative H&E-based histopathologic examination has a false-negative rate of 5% to 52% (reviewed in ref. 11). Furthermore, these methods provide subjective rather than objective results, which may differ from one pathologist to another (12). On the other hand, the definitive postoperative histopathologic examination generally requires 5 to 10 days for assessment. If an accurate Imaging, Diagnosis, Prognosis

We show that structural changes of a guest molecule can trigger structural transformations of a crystalline host framework. Azobenzene was introduced into a flexible porous coordination polymer (PCP), and cis/trans isomerizations of the guest azobenzene by light or heat successfully induced structural transformations of the host PCP in a reversible fashion. This guest-to-host structural transmission resulted in drastic changes in the gas adsorption property of the host-guest composite, displaying a new strategy for creating stimuli-responsive porous materials.

Although histologic definition of follicular thyroid lesions is readily available, application of the diagnostic criteria and personal experience may lead to disagreement among pathologists. To investigate interobserver variation in assessment of encapsulated follicular lesions, eight pathologists (four American and four Japanese) reviewed the same hematoxylin and eosin-stained slide of each of 21 cases of thyroid lesions showing encapsulation and follicular growth pattern. In 10% of the cases, there was complete agreement. At least seven pathologists agreed on the diagnosis in 29% of the cases, and at least six in 76% of the cases. American and Japanese pathologists agreed among themselves in 33% and 52% of cases, respectively. The frequency of diagnosis of adenomatous goiter among Japanese pathologists (31%) was considerably higher than that among American pathologists (6%). In contrast, the frequency of diagnosis (25%) of papillary carcinoma among American pathologists was considerably higher than that (4%) among Japanese pathologists. Our analysis revealed three main factors affecting observer variation: 1) interpretation of the significance of microfollicles intimately related to capillaries within the tumor capsule, 2) evaluation of what constituted the type of nuclear clearing indicative of papillary carcinoma, and 3) absence of clear morphologic criteria for separation of adenomatous goiter and follicular adenoma. To reduce observer variation of encapsulated follicular lesions, it will be necessary to provide more explicit criteria for diagnosis.

In order to elucidate the clinical significance of the erbB family, epidermal growth factor receptor (EGF-R), c-erbB-2, c-erbB-3 and c-erbB-4 in hepatocellular carcinoma (HCC), we investigated the expression of these proteins by means of immunohistochemistry for HCC as well as adjacent noncancerous lesions. EGF-R was expressed in 68% of the HCC examined and showed correlation with the proliferating activity, stage, intrahepatic metastasis and carcinoma differentiation. c-erbB-2 was expressed in only 21% of the cases and showed no relationships with the clinicopathological parameters. c-erbB-3 protein was observed in 84% of the HCC and 38.1% of the noncancerous lesions. Its expression in HCC was equal to or greater than noncancerous lesions in 90.5% of the cases, and was related to the stage, portal invasion, cell proliferating activity, tumour size, intrahepatic metastasis and carcinoma differentiation. c-erbB-4 protein was expressed in 61.0% of HCC and in as much as 86.1% of the noncancerous lesions. Unlike the expression of c-erbB-3, that of c-erbB-4 in HCC was less than that of the adjacent noncancerous lesions in 51.2% of the cases. No statistical significance could be established between this protein expression in HCC and clinicopathological features. EGF-R and c-erbB-3 affected disease-free survival, but were not recognized as independent prognostic factors by multivariate analysis. The present study suggests that, of the four receptors, EGF-R and c-erbB-3 play important roles in the progression of HCC. © 2001 Cancer Research Campaign www.bjcancer.com

The structural and electronic properties of BiCoO(3) under high pressure have been investigated. Synchrotron X-ray and neutron powder diffraction studies show that the structure changes from a polar PbTiO(3) type to a centrosymmetric GdFeO(3) type above 3 GPa with a large volume decrease of 13% at room temperature revealing a spin-state change. The first-order transition is accompanied by a drop of electrical resistivity. Structural results show that Co(3+) is present in the low spin state at high pressures, but X-ray emission spectra suggest that the intermediate spin state is present. The pressure-temperature phase diagram of BiCoO(3) has been constructed enabling the transition temperature at ambient pressure to be estimated as 800-900 K.

Band gap opening and engineering is one of the high priority goals in the development of graphene electronics. Here, we report on the opening and scaling of band gap in BN doped graphene (BNG) films grown by low-pressure chemical vapor deposition method. High resolution transmission electron microscopy is employed to resolve the graphene and h-BN domain formation in great detail. X-ray photoelectron, micro-Raman, and UV-vis spectroscopy studies revealed a distinct structural and phase evolution in BNG films at low BN concentration. Synchrotron radiation based XAS-XES measurements concluded a gap opening in BNG films, which is also confirmed by field effect transistor measurements. For the first time, a significant band gap as high as 600 meV is observed for low BN concentrations and is attributed to the opening of the π-π* band gap of graphene due to isoelectronic BN doping. As-grown films exhibit structural evolution from homogeneously dispersed small BN clusters to large sized BN domains with embedded diminutive graphene domains. The evolution is described in terms of competitive growth among h-BN and graphene domains with increasing BN concentration. The present results pave way for the development of band gap engineered BN doped graphene-based devices.

Metastasis to the regional lymph nodes through the lymphatic vessels is a common step in the progression of cancer and an important prognostic factor in many types of cancer. Recent evidence suggests that VEGF-C promotes lymphangiogenesis, and that tumor lymphangiogenesis in turn promotes lymphatic metastasis. We have studied the role of LVD in breast cancer, and examined whether LVD is associated with lymph node metastasis, VEGF-C expression, or prognosis. In addition, we examined whether VEGF-C mRNA transcript levels were associated with lymph node metastasis and LVD. We began by investigating the lymphatics in primary human breast carcinoma with long-term follow-up (113 cases of invasive ductal and other breast cancers) by quantitative immunohistochemical staining for podoplanin. We then analyzed the relationship between LVD and lymph node status as well as VEGF-C immunoreactivity and other established clinicopathological parameters. The relationship between LVD and prognosis was also studied. VEGF-C mRNA transcript levels were examined by quantitative real-time RT-PCR, in 55 invasive ductal breast carcinomas. This was followed by an analysis of the relationship between VEGF-C mRNA transcript levels and lymph node metastasis as well as LVD. Mean LVD of 'hot spots' was 10.2 +/- 7.4/each case. LVD was significantly correlated with lymph node metastasis (p < 0.0001), VEGF-C immunoreactivity (p = 0.0084), and podoplanin positive lymphatic invasion (p < 0.0001). Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that high LVD was associated with both worse disease free survival (p = 0.0033) and overall survival (p = 0.0391). VEGF-C mRNA transcript levels were also correlated with lymph node metastasis (p = 0.0074) and LVD (p = 0.0409). Increased LVD was correlated with lymph node metastasis and VEGF-C expression. High LVD may be a significant unfavorable prognostic factor for long-term survival in breast cancer.

Purpose: Accurate assessment of metastasis in sentinel lymph nodes (SLN) of breast cancer is important but involves a heavy workload for the pathologist.We conducted a multicenter clinical trial in Japan to evaluate a new automated assay system for cytokeratin 19 mRNA, the one-step nucleic acid amplification (OSNA) assay (Sysmex), to detect lymph node metastasis of breast cancer. Experimental Design: Surgically obtained axillary lymph nodes were sectioned into four pieces, two of which were examined with the OSNA assay. The other two adjacent pieces were examined with H&E and immunohistochemical staining for cytokeratin 19. Serial sections at 0.2-mm intervals were used in trial 1 to determine the specificity of the OSNA assay, and three pairs of sections cut from the sliced surfaces of the pieces were used in trial 2 to compare the accuracy of the OSNA assay with that of a routine pathologic examination for SLNs in Japan. Results: In trial 1, the sensitivity and specificity were 95.0% [95% confidence interval (95% CI), 75.1-99.9 %] and 97.1% (95 % CI, 91.8-99.4%), respectively, for 124 axillary lymph nodes obtained from 34 patients. In trial 2, the agreement between findings of the assay and of the pathologic examination was 92.9% (95% CI, 90.1-95.1%) for 450 axillary lymph nodes obtained from 164 patients. Conclusion: The OSNA assay can detect lymph node metastasis as accurately as can conventional pathology and thus can be an effective addition to or alternative for rapid intraoperative examination of SLNs.Sentinel lymph node (SLN) biopsy for breast cancer is expected to become a standard surgical procedure in the near future, and accurate assessment of metastasis of SLNs is essential for making decisions about the avoidance of unnecessary axillary dissection and the provision of appropriate adjuvant treatment for patients. However, methods for the pathologic examination of SLNs to detect metastasis remain controversial (1 -4). Although more detailed examination of SLNs can provide more accurate information about metastasis (5), to obtain more accurate results, a comparatively greater number of pathologic specimens need to be examined (6). This involves much time for preparation of the specimens and a heavy workload for pathologists to examine them, especially intraoperatively.To overcome these problems, molecular detection of metastasis has been developed as one of the most promising methods for SLN examination. With this procedure, the whole lymph node can be examined during a short time