Abstract
Tuberous sclerosis complex (TSC) results from mutation of . TSC1 or . TSC2 that encode for hamartin and tuberin. It affects the kidneys often in advance of extra-renal stigmata. We studied 14 TSC cases, and 4 possible TSC cases with multiple angiomyolipomas (AMLs) for hamartin and tuberin protein expression to determine if the staining profile could predict mutation status or likelihood of TSC with renal-limited disease. The 18 cases included 15 nephrectomies and 1 section of 6 TSC-associated renal cell carcinomas (RCC). Controls included the non-neoplastic kidney in 5 tumor nephrectomies, 4 sporadic cases of AML and 6 clear cell RCCs. In the 14 TSC cases, 9 had AMLs, 9 had RCCs, 5 had polycystic kidney disease and 8 had eosinophilic cysts (EC) lined by large eosinophilic cells. The controls and study cases showed luminal staining of proximal tubules (PT) and peripheral membrane staining in distal tubules/collecting ducts for hamartin and cytoplasmic staining for tuberin. Eosinophilic cysts had a luminal PT-like stain with hamartin and a cytoplasmic reaction for tuberin. Hamartin stained myoid cells in all AMLs. Tuberin was negative in all but 1AML, an epithelioid AML. All but 1 RCC were positive for tuberin; 13 RCCs (7 TSC/6 non-TSC) were negative for hamartin and 4 showed a weak reaction. We conclude that the ECs of TSC are proximal tubule-derived. The hamartin and tuberin staining profiles of AMLs and most RCCs are reciprocal precluding prediction of the mutation in TSC, and fail to predict if a patient with multifocal AML has TSC.
| Original language | English (US) |
|---|---|
| Journal | Pathology Research and Practice |
| DOIs | |
| State | Accepted/In press - Jan 20 2016 |
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Keywords
- Angiomyolipoma
- Hamartin
- Polycystic kidney disease
- Renal cell carcinoma
- Tuberin
- Tuberous sclerosis complex
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Cell Biology
Cite this
Tuberous sclerosis complex : Hamartin and tuberin expression in renal cysts and its discordant expression in renal neoplasms. / Bonsib, Stephen M.; Boils, Christie; Gokden, Neriman; Grignon, David; Gu, Xin; Higgins, John P T; Leroy, Xavier; McKenney, Jesse K.; Nasr, Samih H.; Phillips, Carrie; Sangoi, Ankur R.; Wilson, Jon; Zhang, Ping L.
In: Pathology Research and Practice, 20.01.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tuberous sclerosis complex
T2 - Hamartin and tuberin expression in renal cysts and its discordant expression in renal neoplasms
AU - Bonsib, Stephen M.
AU - Boils, Christie
AU - Gokden, Neriman
AU - Grignon, David
AU - Gu, Xin
AU - Higgins, John P T
AU - Leroy, Xavier
AU - McKenney, Jesse K.
AU - Nasr, Samih H.
AU - Phillips, Carrie
AU - Sangoi, Ankur R.
AU - Wilson, Jon
AU - Zhang, Ping L.
PY - 2016/1/20
Y1 - 2016/1/20
N2 - Tuberous sclerosis complex (TSC) results from mutation of . TSC1 or . TSC2 that encode for hamartin and tuberin. It affects the kidneys often in advance of extra-renal stigmata. We studied 14 TSC cases, and 4 possible TSC cases with multiple angiomyolipomas (AMLs) for hamartin and tuberin protein expression to determine if the staining profile could predict mutation status or likelihood of TSC with renal-limited disease. The 18 cases included 15 nephrectomies and 1 section of 6 TSC-associated renal cell carcinomas (RCC). Controls included the non-neoplastic kidney in 5 tumor nephrectomies, 4 sporadic cases of AML and 6 clear cell RCCs. In the 14 TSC cases, 9 had AMLs, 9 had RCCs, 5 had polycystic kidney disease and 8 had eosinophilic cysts (EC) lined by large eosinophilic cells. The controls and study cases showed luminal staining of proximal tubules (PT) and peripheral membrane staining in distal tubules/collecting ducts for hamartin and cytoplasmic staining for tuberin. Eosinophilic cysts had a luminal PT-like stain with hamartin and a cytoplasmic reaction for tuberin. Hamartin stained myoid cells in all AMLs. Tuberin was negative in all but 1AML, an epithelioid AML. All but 1 RCC were positive for tuberin; 13 RCCs (7 TSC/6 non-TSC) were negative for hamartin and 4 showed a weak reaction. We conclude that the ECs of TSC are proximal tubule-derived. The hamartin and tuberin staining profiles of AMLs and most RCCs are reciprocal precluding prediction of the mutation in TSC, and fail to predict if a patient with multifocal AML has TSC.
AB - Tuberous sclerosis complex (TSC) results from mutation of . TSC1 or . TSC2 that encode for hamartin and tuberin. It affects the kidneys often in advance of extra-renal stigmata. We studied 14 TSC cases, and 4 possible TSC cases with multiple angiomyolipomas (AMLs) for hamartin and tuberin protein expression to determine if the staining profile could predict mutation status or likelihood of TSC with renal-limited disease. The 18 cases included 15 nephrectomies and 1 section of 6 TSC-associated renal cell carcinomas (RCC). Controls included the non-neoplastic kidney in 5 tumor nephrectomies, 4 sporadic cases of AML and 6 clear cell RCCs. In the 14 TSC cases, 9 had AMLs, 9 had RCCs, 5 had polycystic kidney disease and 8 had eosinophilic cysts (EC) lined by large eosinophilic cells. The controls and study cases showed luminal staining of proximal tubules (PT) and peripheral membrane staining in distal tubules/collecting ducts for hamartin and cytoplasmic staining for tuberin. Eosinophilic cysts had a luminal PT-like stain with hamartin and a cytoplasmic reaction for tuberin. Hamartin stained myoid cells in all AMLs. Tuberin was negative in all but 1AML, an epithelioid AML. All but 1 RCC were positive for tuberin; 13 RCCs (7 TSC/6 non-TSC) were negative for hamartin and 4 showed a weak reaction. We conclude that the ECs of TSC are proximal tubule-derived. The hamartin and tuberin staining profiles of AMLs and most RCCs are reciprocal precluding prediction of the mutation in TSC, and fail to predict if a patient with multifocal AML has TSC.
KW - Angiomyolipoma
KW - Hamartin
KW - Polycystic kidney disease
KW - Renal cell carcinoma
KW - Tuberin
KW - Tuberous sclerosis complex
UR - http://www.scopus.com/inward/record.url?scp=84994791409&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84994791409&partnerID=8YFLogxK
U2 - 10.1016/j.prp.2016.04.005
DO - 10.1016/j.prp.2016.04.005
M3 - Article
JO - Pathology Research and Practice
JF - Pathology Research and Practice
SN - 0344-0338
ER -