Chiaki Yoshikawa

Vinculin: Its Possible Use as a Marker of Normal Collecting Ducts and Renal Neoplasms with Collecting Duct System Phenotype

Vinculin is a cytoskeletal protein associated with membrane actin-filament-attachment sites of cell-cell and cell-matrix adherens-type junctions. In this article, we examine the expression of vinculin to elucidate its role in human renal neoplasms. We reviewed surgically resected specimens and selected available tissue from 79 renal tumors in 78 patients. There were 55 men and 23 women. Their mean age was 61 years and the mean size of the renal tumors was 6.1 cm. All renal tumors were examined by immunohistochemistry using a monoclonal antibody against vinculin. Overall, 17 (21.5%) renal tumor samples reacted with vinculin. The positive ratio in various types of renal tumors was as follows: conventional-type (clear cell), 0/54; papillary-type, 5/12; chromophobe-type, 5/5; sarcomatoid-type, 3/4; collecting duct carcinoma, 3/3; and oncocytoma, 1/1. The positive rate of conventional-type renal cell carcinomas (RCCs) is significantly different from that of other renal tumors (P < .01). Normal kidney, conventional, and papillary-type RCCs exhibited positive signals in Western blot analysis. These results suggest that vinculin may serve as a useful marker of renal neoplasms with collecting duct system phenotype such as chromophobe-type RCC.

Overexpression of c-met proto-oncogene associated with chromophilic renal cell carcinoma with papillary growth.

Abstract Various genetic changes are involved in human renal cell carcinomas (RCCs). However, the molecular events related to other cytomorphological subtypes of RCC are not well known, apart from the relationship between the von Hippel-Lindau tumour suppressor gene and clear cell subtype RCC. We examined the overexpression of several growth factor receptors immunohistochemically and analyzed their relationship to the cytomorphological characters in 120 cases of RCCs. These receptors included c-met proto-oncogene product (c-MET), epidermal growth factor receptor (EGFR) and transforming growth factor beta receptor II (TGFβR). The overexpression of c-MET was detected in all cases (20/20) of the tubulo-papillary growth type and 78.3% (18/23) of chromophilic cell subtype, resulting in a very significant associations between c-MET overexpression and tubulo-papillary growth RCCs (P<0.0001), c-MET and chromophilic subtype RCCs (P<0.0001), and c-MET and EGFR (P<0.0001). EGFR overexpression was significantly associated with the compact growth RCCs (49/89, P<0.0001), clear cell subtype RCCs (P<0.005) and the overexpression of TGFβR (P<0.0001). These results strongly suggest a close correlation between the overexpression of c-MET and development of the chromophilic subtype of RCC with papillary growth pattern. EGFR expression is closely related to the pathogenesis of the clear cell subtype of RCC with compact growth pattern. The overexpression of c-MET, EGFR, and TGFβR may have roles that are individually significant in the morphogenesis of RCC.

Paxillin: application of immunohistochemistry to the diagnosis of chromophobe renal cell carcinoma and oncocytoma.

Paxillin is a cytoskeletal protein that was recently identified as a component of focal adhesions and links between F-actin and integrin. In this study, 91 renal tumors—65 conventional renal cell carcinomas (RCCs), 14 papillary RCCs, 6 chromophobe RCCs, 4 collecting duct carcinomas, 2 oncocytomas—were investigated for the immunohistochemical expression of paxillin. In a normal kidney, paxillin was predominantly expressed in the cytoplasm of distal tubules, loops of Henle, collecting ducts, and vascular smooth muscle cells. In all of the chromophobe RCCs and oncocytomas, strong expression of paxillin was observed in the tumor cytoplasm. In contrast to these tumors, conventional RCCs, papillary RCCs, and collecting duct carcinomas showed negative reactions for paxillin except for one case in each subgroup with weak reactivity. An immunoblot analysis confirmed the presence of paxillin in healthy kidney, chromophobe RCC, and oncocytoma. These data suggest that paxillin possibly plays a role in signal transductions as a focal adhesion intervening between tumor cells and the extracellular matrix in renal tumors with collecting duct phenotypes such as chromophobe RCCs and oncocytomas, but not in conventional RCCs. In addition, paxillin may be an available marker in distinguishing chromophobe RCCs from conventional or papillary RCCs.

Numerical Chromosomal Changes in Metastatic Prostate Cancer Following Anti-Androgen Therapy: Fluorescence In Situ Hybridization Analysis of 5 Japanese Cases

We used fluorescence in situ hybridization with centromere-specific probes for chromosomes 7, 8, 10, and Y to determine the copy number of these chromosomes in metastatic prostate cancers of five Japanese cases. Freshly prepared samples were obtained from prostate needle biopsies at different phases of clinical treatment; pretreatment, 1 week, 4 weeks, 12 weeks, 24 weeks post-treatment (PT), and clinical relapse. Gain of chromosomes 7 and 8, as noted in pretreatment samples; however, in post-treatment specimens (four of five cases), a remarkable reduction in the number of cells with extra copies of these chromosomes was detected. This decrease in the number of cells with additional chromosome 7 and 8 signals was correlated with the clinicohistopathological findings until 4 weeks PT. Chromosomes Y and 10 did not show numerical aberrations before treatment or changes in cells with aneusomy after treatment in all five cases. Our results suggest that gains of chromosomes 7 and 8 correlate with high grade and stage, and that changes in the cell number with aneusomy of chromosomes 7 and 8 reflect the clinical effects of anti-androgen therapy at an early phase, which may also indicate the androgen dependency of prostate cancer cells.