J Korean Med Sci.  2007 Apr;22(2):305-310. 10.3346/jkms.2007.22.2.305.

Claudin-7 is Highly Expressed in Chromophobe Renal Cell Carcinoma and Renal Oncocytoma

Affiliations
  • 1Department of Pathology, Chonnam National University Medical School, 5 Hak-dong, Dong-gu, Gwangju, Korea. cchoi@chonnam.ac.kr
  • 2Department of Urology, Kwangju Christian Hospital, Gwangju, Korea.
  • 3Department of Surgery, Chonnam National University Medical School, Gwangju, Korea.
  • 4Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
  • 5Department of Pathology, Dong-A University College of Medicine, Busan, Korea.
  • 6Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
  • 7Department of Pathology, The Methodist Hospital, Houston, Texas, U.S.A.

Abstract

Claudin-7 has recently been suggested to be a distal nephron marker. We tested the possibility that expression of claudin-7 could be used as a marker of renal tumors originating from the distal nephron. We examined the immunohistochemical expression of claudin-7 and parvalbumin in 239 renal tumors, including 179 clear cell renal cell carcinoma (RCC)s, 29 papillary RCCs, 20 chromophobe RCCs, and 11 renal oncocytomas. In addition, the methylation specific-PCR (MSP) of claudin-7 was performed. Claudin-7 and parvalbumin immunostains were positive in 3.4%, 7.8% of clear cell RCCs, 34.5%, 31.0% of papillary RCCs, 95.0%, 80.0% of chromophobe RCCs, and 72.7%, 81.8% of renal oncocytomas, respectively. The sensitivity and specificity of claudin-7 in diagnosing chromophobe RCC among subtypes of RCC were 95.0% and 92.3%. Those of parvalbumin were 80.0% and 88.9%. The expression pattern of claudin-7 was mostly diffuse in chromophobe RCC and was either focal or diffuse in oncocytoma. All of the cases examined in the MSP revealed the presence of unmethylated promoter of claudin-7 without regard to claudin-7 immunoreactivity. Hypermethylation of the promoter might not be the underlying mechanism for loss of its expression in RCC. Claudin-7 can be used as a useful diagnostic marker in diagnosing chromophobe RCC and oncocytoma.

Keyword

Chromophobe Renal Cell Carcinoma; Oncocytoma; Claudin-7

MeSH Terms

Tumor Markers, Biological/metabolism
Tumor Cells, Cultured
Tissue Distribution
Sensitivity and Specificity
Reproducibility of Results
Nephrons/metabolism
Neoplasm Proteins/metabolism
Membrane Proteins/analysis/*metabolism
Kidney Neoplasms/*diagnosis/*metabolism
Humans
Carcinoma, Renal Cell/*diagnosis/*metabolism
Adenoma, Oxyphilic/*diagnosis/*metabolism

Figure

  • Fig. 1 Immunohistochemical stains of claudin-7 and parvalbumin. Hematoxylin and eosin stains of normal renal cortex (A), clear cell RCC (B), papillary RCC (C), chromophobe RCC (D), and renal oncocytoma (E) are shown. Claudin-7 is expressed in the distal nephron of normal renal cortex with a distinct membranous pattern (F). It is diffusely expressed in papillary RCC (H) and chromophobe RCC (I), and is focally expressed in oncocytoma (J). It is not expressed in clear cell RCC (G). Parvalbumin is expressed in the cytoplasm of the distal nephron of normal renal cortex (K). It is diffusely expressed in papillary RCC (M), chromophobe RCC (N), and oncocytoma (O). It is not expressed in conventional RCC (L) (A-O, ×200).

  • Fig. 2 Methylation-specific PCR of claudin-7. Primer sets used for amplification are designated as un-methylated (U), and methylated (M). The methylated control DNA (MC), and un-methylated control DNA (UMC) are designated. The smaller molecular weight fragments seen in the U and M lanes are primer dimers.


Reference

1. Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, Feuer EJ, Thun MJ. Cancer statistics. CA Cancer J Clin. 2004. 54:8–29.
2. Reuter VE, Presti JC Jr. Contemporary approach to the classification of renal epithelial tumors. Semin Oncol. 2000. 27:124–137.
3. Zambrano NR, Lubensky IA, Merino MJ, Linehan WM, Walther MM. Histopathology and molecular genetics of renal tumors toward unification of a classification system. J Urol. 1999. 162:1246–1258.
Article
4. Cheville JC, Lohse CM, Zincke H, Weaver AL, Blute ML. Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma. Am J Surg Pathol. 2003. 27:612–624.
Article
5. Crotty TB, Farrow GM, Lieber MM. Chromophobe cell renal carcinoma: clinicopathological features of 50 cases. J Urol. 1995. 154:964–967.
Article
6. Storkel S, Steart PV, Drenckhahn D, Thoenes W. The human chromophobe cell renal carcinoma: its probable relation to intercalated cells of the collecting duct. Virchows Arch B Cell Pathol Incl Mol Pathol. 1989. 56:237–245.
7. Abrahams NA, MacLennan GT, Khoury JD, Ormsby AH, Tamboli P, Doglioni C, Schumacher B, Tickoo SK. Chromophobe renal cell carcinoma: a comparative study of histological, immunohistochemical and ultrastructural features using high throughput tissue microarray. Histopathology. 2004. 45:593–602.
Article
8. Avery AK, Beckstead J, Renshaw AA, Corless CL. Use of antibodies to RCC and CD10 in the differential diagnosis of renal neoplasm. Am J Surg Pathol. 2000. 24:203–210.
9. Khoury JD, Abrahams NA, Levin HS, MacLennan GT. The utility of epithelial membrane antigen and vimentin in the diagnosis of chromophobe renal cell carcinoma. Ann Diagn Pathol. 2002. 6:154–158.
Article
10. Tickoo SK, Amin MB, Linden MD, Lee MW, Zarbo RJ. Antimitochondrial antibody (113-1) in the differential diagnosis of granular renal cell tumors. Am J Surg Pathol. 1997. 21:922–930.
11. Tickoo SK, Amin MB, Zarbo RJ. Colloidal iron staining in renal epithelial neoplasms, including chromophobe renal cell carcinoma: emphasis on technique and patterns of staining. Am J Surg Pathol. 1998. 22:419–424.
12. Wu SL, Kothari P, Wheeler TM, Reese T, Connelly JH. Cytokeratins 7 and 20 immunoreactivity in chromophobe renal cell carcinomas and renal oncocytomas. Mod Pathol. 2002. 15:712–717.
Article
13. Martignoni G, Pea M, Chilosi M, Brunelli M, Scarpa A, Colato C, Tardanico R, Zamboni G, Bonetti F. Parvalbumin is constantly expressed in chromophobe renal carcinoma. Mod Pathol. 2001. 14:760–767.
Article
14. Tsukita S, Furuse M. Occludin and claudins in tight-junction strands: leading or supporting players? Trends Cell Biol. 1999. 9:268–273.
Article
15. Mitic LL, Van Itallie CM, Anderson JM. Molecular physiology and pathophysiology of tight junctions I. Tight junction structure and function: lessons from mutant animals and proteins. Am J Physiol Gastrointest Liver Physiol. 2000. 279:G250–G254.
Article
16. Schuetz AN, Yin-Goen Q, Amin MB, Moreno CS, Cohen C, Hornsby CD, Yang WL, Petros JA, Issa MM, Pattaras JG, Ogan K, Marshall FF, Young AN. Molecular classification of renal tumors by gene expression profiling. J Mol Diagn. 2005. 7:206–218.
Article
17. Taki A, Nakatani Y, Misugi K, Yao M, Nagashima Y. Chromophobe renal cell carcinoma: an immunohistochemical study of 21 Japanese cases. Mod Pathol. 1999. 12:310–317.
18. Kovacs G, Akhtar M, Beckwith BJ, Bugert P, Cooper CS, Delahunt B, Eble JN, Fleming S, Ljungberg B, Medeiros LJ, Moch H, Reuter VE, Rotz E, Roos G, Schmidt D, Srigley JR, Storkel S, van den Berg E, Zbar B. The Heidelberg classification of renal cell tumours. J Pathol. 1997. 183:131–133.
Article
19. Guinan P, Sobin LH, Algaba F, Badellino F, Kameyama S, MacLennan G, Novick A. TNM staging of renal cell carcinoma: Workgroup No. 3. Union International Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer. 1997. 80:992–993.
20. Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982. 6:655–663.
Article
21. Kominsky SL, Argani P, Korz D, Evron E, Raman V, Garrett E, Rein A, Sauter G, Kallioniemi OP, Sukumar S. Loss of the tight junction protein claudin-7 correlates with histological grade in both ductal carcinoma in situ and invasive ductal carcinoma of the breast. Oncogene. 2003. 22:2021–2033.
Article
22. Lee JH, Park SJ, Abraham SC, Seo JS, Nam JH, Choi C, Juhng SW, Rashid A, Hamilton SR, Wu TT. Frequent CpG island methylation in precursor lesions and early gastric adenocarcinomas. Oncogene. 2004. 23:4646–4654.
Article
23. Zheng JY, Yu D, Foroohar M, Ko E, Chan J, Kim N, Chin R, Pang S. Regulation of the expression of the prostate-specific antigen by claudin-7. J Membr Biol. 2003. 194:187–197.
Article
24. Berchtold MW, Epstein P, Beaudet AL, Payne ME, Heizmann CW, Means AR. Structural organization and chromosomal assignment of the parvalbumin gene. J Biol Chem. 1987. 262:8696–8701.
Article
25. Young AN, de Oliveira Salles PG, Lim SD, Cohen C, Petros JA, Marshall FF, Neish AS, Amin MB. Beta defensin-1, parvalbumin, and vimentin: a panel of diagnostic immunohistochemical markers for renal tumors derived from gene expression profiling studies using cDNA microarrays. Am J Surg Pathol. 2003. 27:199–205.
26. Hughson MD, Johnson LD, Silva FG, Kovacs G. Nonpapillary and papillary renal cell carcinoma: a cytogenetic and phenotypic study. Mod Pathol. 1993. 6:449–456.
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