Eighteen hundred and eighty-four cases of human solid tumours and 833 samples of normal human tissues, formalin-fixed and paraffin-embedded, were examined immunohistochemically for expression of c-kit oncogene product using polyclonal antibody against synthesized c-kit peptide. Seminoma/dysgerminoma and small cell lung carcinoma (SCLC) show preferential c-kit expression at 92% and 36% frequency, respectively, whereas only sporadic cases of cervical carcinoma and non-SCLC lung carcinoma show c-kit positivity. A normal tissue counterpart positive for c-kit product is detected in the testis (spermatocyte) and ovary (oocyte) but not in the lung or the cervix. In contrast, normal epithelial cells of the breast, skin basal cells and tissue mast cells harbour c-kit product, but transformed cells of the former two are largely deficient in the c-kit protein. One hundred and thirty-nine neuroendocrine tumours and 39 non-pulmonary small cell carcinomas were all negative, except for two cases of neuroblastoma. This indicates a distinct character for SCLC in c-kit expression. The c-kit product may be a useful marker in diagnostic pathology of seminoma/dysgerminoma and SCLC among human solid tumours, and in distinction of SCLC from non-pulmonary small cell carcinoma.

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It has been demonstrated that the voltammetric in situ application of electromodulated UV-vis reflectance spectroscopy, electroreflectance (ER) voltammetry, is a powerful tool with which to analyze the electrode reaction of an adsorbed species on an electrode surface. The ER response, which in fact originates from the absorbance change with ac modulation of the electrode potential, was theoretically analyzed and simulated as a function of electrode potential. The results of the theory and simulation were compared to the electrode reaction of Nile Blue A adsorbed on a pyrolytic graphite electrode surface. The resulting ER voltammetry was responsive only to the faradaic processes of Nile Blue A adsorbed on a pyrolytic graphite electrode, and its turnover reaction rate was determined to be in the range of 60-120 5-1. It was revealed through ER measurements that the electronic structure as well as the redox reaction mechanism of the adsorbed Nile Blue A on a graphite electrode were significantly different from those of the native dye. IntroductionThe recent development of spectroelectrochemistry has received a great deal of attention. The combined use of in situ spectroscopic techniques and conventional methods has afforded us a detailed understanding of electrode processes on a molecular level.' A variety of structural and mechanistic information is provided, depending on the method of spectroscopy. Infrared reflection absorption spectroscopy (IRRAS) and Raman scattering (RS) spectroscopy offer information about the structural aspects in the vibrational mode, while ultraviolet-visible (UV-vis) absorption spectroscopy offers similar information in an electronic mode. A body of work on the electrode process using UV-vis absorption has been carried out to measure in situ the spectra of species in the solution phase, among which the optically transparent thin-layer electrode (OTTLE) is most widely utilized.2 Attempts have also been made to measure the spectra of the species in the vicinity of the electrode interface by using the internal reflection method with an optically transparent ele~trode.~The reflection method in UV-vis mode to characterize solid surfaces, often referred as electroreflectance (ER), has developed in solid-state physicse4t5 The method has been widely used in the studies of the electronic band structure of semiconductors. In this method, the reflectance change a t the solid surface due to the perturbation of dielectric properties of the surface is detected as a function of the surface electronic field of the solid.The ER technique has also been applied to metal electrode surfaces combined with conventional electrochemical methods where a change in surface charge causes a change in reflectance. For example, Hinnen and her

The correlations among epidermal growth factor receptor (EGFR) gene amplification, gene mutation, overexpression/phosphorylation of EGFR protein and activation of its downstream molecules, signal transducers and activators of transcription 3 (Stat-3), Akt and extracellular signal-related protein kinase 1/2 (Erk1/2) were investigated in 28 cases of human lung carcinomas. In five cases of carcinomas with EGFR amplification, EGFR expression and phosphorylation levels were higher than other cases, and Stat-3 was activated in all five cases. Point mutations in the tyrosine kinase domain of EGFR were detected in five cases, one of which was also associated with gene amplification. In these five cases, both EGFR expression and phosphorylation were enhanced, and Akt was activated in four cases. In the remaining 19 cases, EGFR protein expression was upregulated in eight cases and phosphorylated in four cases, but neither EGFR nor phosphorylated-EGFR expression levels specifically correlated with activation of particular downstream molecules. In general, either Stat-3 or Akt, but not both, was activated reciprocally and complementarily to each other, as indicated by their phosphorylation. However, Erk1/2 was activated regardless of the status of Stat-3, Akt or EGFR proteins. The current data suggest that persistent Stat-3 activation may be a critical event downstream of EGFR that has been overexpressed by gene amplification. In contrast, tumor cells harboring the EGFR mutation may persistently activate a cascade via Akt. Finally, in the majority of cases that have no aberration of the EGFR, its downstream molecules function in reciprocal and/or complementary manner in the maintenance and/or progression of carcinomas. These overall results could provide novel insights into potential chemotherapeutic regimens for lung carcinomas, such as inhibitors of Stat-3, Akt and Erk1/2.

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