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Distinctive expression patterns of glycoprotein non-metastatic B and folliculin in renal tumors in patients with Birt-Hogg-Dubé syndrome.

Furuya M, Hong SB, Tanaka R, Kuroda N, Nagashima Y, Nagahama K, Suyama T, Yao M, Nakatani Y - Cancer Sci. (2015)

Bottom Line: Western blot and immunostaining analyses revealed that FLCN-related RCCs showed overexpression of GPNMB and underexpression of FLCN, whereas sporadic tumors showed inverted patterns.GPNMB mRNA in FLCN-related RCCs was 23-fold more abundant than in sporadic tumors.The distinctive expression patterns of GPNMB and FLCN might identify patients with RCCs who need further work-up for BHD.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

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Glycoprotein non-metastatic B (GPNMB) immunostaining of Birt–Hogg–Dubé (BHD) and sporadic tumors. (a, c, e) H&E staining of BHD tumors (T) of patients BHD2-T1 (a), BHD13-T1 (c), and a nodule of oncocytosis in the normal-looking region (N) of BHD13 (e, dotted circle). (b, d, f) Serial sections of (a, c, e) immunostained for GPNMB. Tumor cells (b, d) were intensely stained for GPNMB. Tubules of normal-looking regions were negative for GPNMB. GPNMB was immunostained in the region of focal oncocytosis (f, dotted circle). (g–i) Immunostaining for GPNMB in sporadic renal tumors: papillary renal cell carcinoma (g), oncocytoma (h), and chromophobe renal cell carcinoma (i). Insets are H&E stains of the serial sections.
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fig06: Glycoprotein non-metastatic B (GPNMB) immunostaining of Birt–Hogg–Dubé (BHD) and sporadic tumors. (a, c, e) H&E staining of BHD tumors (T) of patients BHD2-T1 (a), BHD13-T1 (c), and a nodule of oncocytosis in the normal-looking region (N) of BHD13 (e, dotted circle). (b, d, f) Serial sections of (a, c, e) immunostained for GPNMB. Tumor cells (b, d) were intensely stained for GPNMB. Tubules of normal-looking regions were negative for GPNMB. GPNMB was immunostained in the region of focal oncocytosis (f, dotted circle). (g–i) Immunostaining for GPNMB in sporadic renal tumors: papillary renal cell carcinoma (g), oncocytoma (h), and chromophobe renal cell carcinoma (i). Insets are H&E stains of the serial sections.

Mentions: Immunostaining revealed that GPNMB was undetectable in normal control kidneys (Fig.6). All FLCN-related RCCs (except for three non-chromophobe RCCs) were positively stained for GPNMB (Table2, Fig.6b,d). Immunostaining intensities of GPNMB were correlated with the relative expression of GPNMB mRNA, such that BHD15 with intense staining showed the highest expression whereas BHD2 with moderate staining showed lower expression compared with BHD15. Small nodules of renal oncocytosis in non-tumor regions, which is one of the diagnostic characteristics of BHD kidneys,5 also showed moderate immunostaining (Fig.6f). In sporadic cases, half of the chromophobe RCCs and most other types were negatively stained for GPNMB (Table3). Importantly, all sporadic oncocytomas were negative for GPNMB, whereas all HOCTs in BHD were positively stained. With regard to GPNMB-positive RCCs, all but one showed nuclear staining for FLCN. Only one GPNMB-positive RCC showed cytoplasmic staining for FLCN. The patient with this tumor also had a few pulmonary cysts. Genetic testing was carried out and the possibility of BHD was eliminated.


Distinctive expression patterns of glycoprotein non-metastatic B and folliculin in renal tumors in patients with Birt-Hogg-Dubé syndrome.

Furuya M, Hong SB, Tanaka R, Kuroda N, Nagashima Y, Nagahama K, Suyama T, Yao M, Nakatani Y - Cancer Sci. (2015)

Glycoprotein non-metastatic B (GPNMB) immunostaining of Birt–Hogg–Dubé (BHD) and sporadic tumors. (a, c, e) H&E staining of BHD tumors (T) of patients BHD2-T1 (a), BHD13-T1 (c), and a nodule of oncocytosis in the normal-looking region (N) of BHD13 (e, dotted circle). (b, d, f) Serial sections of (a, c, e) immunostained for GPNMB. Tumor cells (b, d) were intensely stained for GPNMB. Tubules of normal-looking regions were negative for GPNMB. GPNMB was immunostained in the region of focal oncocytosis (f, dotted circle). (g–i) Immunostaining for GPNMB in sporadic renal tumors: papillary renal cell carcinoma (g), oncocytoma (h), and chromophobe renal cell carcinoma (i). Insets are H&E stains of the serial sections.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376441&req=5

fig06: Glycoprotein non-metastatic B (GPNMB) immunostaining of Birt–Hogg–Dubé (BHD) and sporadic tumors. (a, c, e) H&E staining of BHD tumors (T) of patients BHD2-T1 (a), BHD13-T1 (c), and a nodule of oncocytosis in the normal-looking region (N) of BHD13 (e, dotted circle). (b, d, f) Serial sections of (a, c, e) immunostained for GPNMB. Tumor cells (b, d) were intensely stained for GPNMB. Tubules of normal-looking regions were negative for GPNMB. GPNMB was immunostained in the region of focal oncocytosis (f, dotted circle). (g–i) Immunostaining for GPNMB in sporadic renal tumors: papillary renal cell carcinoma (g), oncocytoma (h), and chromophobe renal cell carcinoma (i). Insets are H&E stains of the serial sections.
Mentions: Immunostaining revealed that GPNMB was undetectable in normal control kidneys (Fig.6). All FLCN-related RCCs (except for three non-chromophobe RCCs) were positively stained for GPNMB (Table2, Fig.6b,d). Immunostaining intensities of GPNMB were correlated with the relative expression of GPNMB mRNA, such that BHD15 with intense staining showed the highest expression whereas BHD2 with moderate staining showed lower expression compared with BHD15. Small nodules of renal oncocytosis in non-tumor regions, which is one of the diagnostic characteristics of BHD kidneys,5 also showed moderate immunostaining (Fig.6f). In sporadic cases, half of the chromophobe RCCs and most other types were negatively stained for GPNMB (Table3). Importantly, all sporadic oncocytomas were negative for GPNMB, whereas all HOCTs in BHD were positively stained. With regard to GPNMB-positive RCCs, all but one showed nuclear staining for FLCN. Only one GPNMB-positive RCC showed cytoplasmic staining for FLCN. The patient with this tumor also had a few pulmonary cysts. Genetic testing was carried out and the possibility of BHD was eliminated.

Bottom Line: Western blot and immunostaining analyses revealed that FLCN-related RCCs showed overexpression of GPNMB and underexpression of FLCN, whereas sporadic tumors showed inverted patterns.GPNMB mRNA in FLCN-related RCCs was 23-fold more abundant than in sporadic tumors.The distinctive expression patterns of GPNMB and FLCN might identify patients with RCCs who need further work-up for BHD.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Show MeSH
Related in: MedlinePlus