title: Fluorescent and chromogenic in situ hybridization of CEN17q as a potent useful diagnostic marker for Birt-Hogg-Dubé syndrome-associated chromophobe renal cell carcinomas.
abstract: Birt-Hogg-Dubé syndrome (BHD) is a familial disorder associated with a germline mutation of FLCN that is a tumor suppressor gene. Patients with BHD have high risks for developing multiple renal cell carcinomas (RCCs). The frequent histological types are hybrid oncocytic/chromophobe tumors (HOCTs) and chromophobe RCCs. The morphology of HOCTs could alert pathologists to the possibility of BHD. On the other hand, chromophobe RCCs occurring in BHD patients demonstrate positive immunostaining for cytokeratin-7, CD82, and Ksp-cadherin similar to their sporadic counterparts. Highly reliable markers for BHD-associated chromophobe RCCs have not been identified. In the present study, we analyzed the state of chromosome 17 in 18 renal tumors composed of 8 chromophobe RCCs, 7 HOCTs, and 3 papillary RCCs obtained from BHD patients using fluorescent and chromogenic in situ hybridization probes for the centromeric region of chromosome 17 long arm. All chromophobe RCCs and HOCTs were disomic except for 1 chromophobe RCC that showed monosomy. On the other hand, 12 of 14 sporadic chromophobe RCCs were monosomic (P = .0008). The state of chromosomes 2 and 6 were also statistically different (P = .0074 and P = .0007, respectively). Three BHD-associated papillary RCCs demonstrated either trisomy (n = 2) or disomy (n = 1). Three of 5 sporadic papillary RCCs showed trisomy. The results indicate that fluorescent and chromogenic in situ hybridization of the centromeric region of chromosome 17 long arm should be a potent useful marker for chromophobe RCCs in patients who have not been diagnosed with BHD and thereby help to determine whether the cases should be considered for genetic testing.
authors.affiliation: Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Ikuma
authors.initials: I
authors.lastname: Kato
authors.affiliation: Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Iribe
authors.affiliation: Department of Surgical Pathology, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.affiliation: Department of Diagnostic Pathology, Kochi Red Cross Hospital, Kochi 780-8562, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Kuroda
authors.affiliation: Medical Mycology Research Center, Chiba University, Chiba 260-8677, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Department of Diagnostic Pathology, Chiba University Graduate School of Medicine, Chiba 260-8677, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakatani
authors.affiliation: Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hasumi
authors.affiliation: Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yao
authors.affiliation: Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address: mfuruya@yokohama-cu.ac.jp.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Furuya
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D058249:Birt-Hogg-Dube Syndrome / Q000175:diagnosis / Q000235:genetics*; D015820:Cadherins / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000175:diagnosis / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D051861:Kangai-1 Protein / Q000032:analysis; D053552:Keratin-7 / Q000032:analysis; D007680:Kidney Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics; D014314:Trisomy; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C497688:CD82 protein, human; C114483:CDH16 protein, human; D015820:Cadherins; C476078:FLCN protein, human; C507497:KRT7 protein, human; D051861:Kangai-1 Protein; D053552:Keratin-7; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins
keywords: Birt-Hogg-Dubé syndrome (BHD); Chromogenic in situ hybridization; Chromophobe renal cell carcinomas; Chromosome 17q; Folliculin (FLCN)