Tuberous sclerosis complex

Hamartin and tuberin expression in renal cysts and its discordant expression in renal neoplasms

Stephen M. Bonsib, Christie Boils, Neriman Gokden, David Grignon, Xin Gu, John P T Higgins, Xavier Leroy, Jesse K. McKenney, Samih H. Nasr, Carrie Phillips, Ankur R. Sangoi, Jon Wilson, Ping L. Zhang

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 languageEnglish (US)
JournalPathology Research and Practice
DOIs
StateAccepted/In press - Jan 20 2016

Fingerprint

Tuberous Sclerosis
Kidney Neoplasms
Angiomyolipoma
Cysts
Kidney
Staining and Labeling
Nephrectomy
Mutation
tuberous sclerosis complex 2 protein
tuberous sclerosis complex 1 protein
Christianity
Polycystic Kidney Diseases
Sclerosis
Renal Cell Carcinoma
Case-Control Studies
Coloring Agents

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 journalArticle

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. / Tuberous sclerosis complex : Hamartin and tuberin expression in renal cysts and its discordant expression in renal neoplasms. In: Pathology Research and Practice. 2016.
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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.

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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.

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KW - Polycystic kidney disease

KW - Renal cell carcinoma

KW - Tuberin

KW - Tuberous sclerosis complex

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