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Toxicologic Pathology
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Journal Article

Histogenetic Stereological Reconstruction of Rat Basophilic, Clear, and Oncocytic Neoplastic Renal Cell Lesions Using Carbonic Anhydrase Type II-PAS Double-Stained Sections

Hiroyuki Tsuda

Experimental Pathology and Chemotherapy Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104, Japan, htsuda{at}gan2.res.ncc.go.jp

Teruhiko Iwase

Second Department of Pathology, Fujita Health University School of Medicine, Kutsukake-cho, Toyoake, Aichi, Japan

Kazuyuki Matsumoto

Second Department of Pathology, Fujita Health University School of Medicine, Kutsukake-cho, Toyoake, Aichi, Japan

Mitsuya Ito

Second Department of Pathology, Fujita Health University School of Medicine, Kutsukake-cho, Toyoake, Aichi, Japan

Iwao Hirono

Second Department of Pathology, Fujita Health University School of Medicine, Kutsukake-cho, Toyoake, Aichi, Japan

Yoshihisa Nishida

Department of Pediatric Surgery, Fujita Health University School of Medicine, Kutsukake-cho, Toyoake, Aichi, Japan

Nobuo Takasuka

Experimental Pathology and Chemotherapy Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104, Japan

Yoshio Iwahori

Experimental Pathology and Chemotherapy Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104, Japan

Tomonori Ota

Experimental Pathology and Chemotherapy Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104, Japan

Dae Joong Kim

Experimental Pathology and Chemotherapy Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104, Japan

Bernhard Kadenbach

Fachbereich Chemie der Philips-Universitst, Hans-Meerwein-Stra§e, Lahnberge, D-3550 Marburg, Germany

The histogenesis of 3 types of rat renal cell tumors (basophilic cell, clear cell, and oncocytic) was stereologically analyzed, with particular attention paid to transitions from normal tubules. Early nitrosamine-induced preneoplastic lesions, including dysplastic tubules (altered tubules), epithelial hyperplasias, and small adenomas, were reconstructed using serially sectioned specimens processed for carbonic anhydrase type II (CA) and periodic acid-Schiff (PAS) (CA-PAS) double staining to allow easier distinction of the nephron segments: Proximal tubules had a PAS-positive brush border and were weakly positive for CA in the cytoplasm; distal tubules were PAS negative and weakly positive for CA; collecting ducts were PAS negative and strongly positive for CA. Similarly, cytochrome c oxidase (CytOx) and CytOx-PAS double staining was also applied to confirm the character of oncocytic lesions. All basophilic lesions (7 of 7) showed transition to proximal tubules. Clear cell lesions positive for CA, on the other hand, showed transition to distal tubules in 4 of 9 (44.4%) lesions and to collecting ducts in 4 of 9 (44.4%) lesions, but in only 1 of 9 (11%) to a proximal tubule. All oncocytic lesions (16 of 16), characterized by positivity for both CA and CytOx, showed transition to collecting ducts. The results indicate that the origins of renal cell neoplasia are proximal tubules for the basophilic cell lesions, either proximal or distal tubules for their clear cell counterparts, and collecting ducts for oncocytic lesions.

Key Words: Renal cell tumor • histogenesis • stereological reconstruction • carbonic anhydrase-PAS • cytochrome c oxidase-PAS

Toxicologic Pathology, Vol. 26, No. 6, 769-776 (1998)
DOI: 10.1177/019262339802600609
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