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Hum Pathol. 2016 Jun;52:74-82. doi: 10.1016/j.humpath.2016.01.004. Epub 2016 Feb 4.

Fluorescent and chromogenic in situ hybridization of CEN17q as a potent useful diagnostic marker for Birt-Hogg-Dubé syndrome-associated chromophobe renal cell carcinomas.

Author information

1
Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
2
Department of Surgical Pathology, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
3
Department of Diagnostic Pathology, Kochi Red Cross Hospital, Kochi 780-8562, Japan.
4
Medical Mycology Research Center, Chiba University, Chiba 260-8677, Japan.
5
Department of Diagnostic Pathology, Chiba University Graduate School of Medicine, Chiba 260-8677, Japan.
6
Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
7
Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. Electronic address: mfuruya@yokohama-cu.ac.jp.

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.

KEYWORDS:

Birt-Hogg-Dubé syndrome (BHD); Chromogenic in situ hybridization; Chromophobe renal cell carcinomas; Chromosome 17q; Folliculin (FLCN)

PMID:
26980015
DOI:
10.1016/j.humpath.2016.01.004
[Indexed for MEDLINE]

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