title: Tuberous sclerosis complex: Hamartin and tuberin expression in renal cysts and its discordant expression in renal neoplasms.
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.
authors.affiliation: Nephropath, 10810 Executive Center Drive, Suite 100, Little Rock, AR, 72211, United States. Electronic address: stephen.bonsib@nephropath.com.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Bonsib
authors.affiliation: Nephropath, 10810 Executive Center Drive, Suite 100, Little Rock, AR, 72211, United States. Electronic address: christie.boils@nephropath.com.
authors.forename: Christie
authors.initials: C
authors.lastname: Boils
authors.affiliation: University of Arkansas, 4301 West Markham, Little Rock, AR, 72205, United States. Electronic address: ngokden@uams.edu.
authors.forename: Neriman
authors.initials: N
authors.lastname: Gokden
authors.affiliation: Indiana University, 350 West 11th Street (Room 6014 Grignon, and Room 4090 phillips) Indianapolis, IN, 46202-4108, United States. Electronic address: dgrignon@iupui.edu.
authors.forename: David
authors.initials: D
authors.lastname: Grignon
authors.affiliation: Louisiana State University, 1501 Kings Hwy, Shreveport, LA, 71103, United States. Electronic address: xgu@lsuhsc.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Gu
authors.affiliation: Stanford University, 300 Pasteur Dr, H2110 MC 5324, Stanford, CA, 94305, United States. Electronic address: john.higgins@stanford.edu.
authors.forename: John P T
authors.initials: JP
authors.lastname: Higgins
authors.affiliation: Lille University Hospitals, Department of Pathology, CHRU, Parc Eurasante, Nord, Lille, 59037, France. Electronic address: x-leroy@chru-lille.fr.
authors.forename: Xavier
authors.initials: X
authors.lastname: Leroy
authors.affiliation: Cleveland Clinic, 9500 Euclid Ave., LL2-1, Cleveland, OH, 44106, United States. Electronic address: mckennj@ccf.org.
authors.forename: Jesse K
authors.initials: JK
authors.lastname: McKenney
authors.affiliation: Mayo Clinic, 200 1st Street South West, Rochester, MN, 55905, United States. Electronic address: nasr.samih@mayo.edu.
authors.forename: Samih H
authors.initials: SH
authors.lastname: Nasr
authors.affiliation: Indiana University, 350 West 11th Street (Room 6014 Grignon, and Room 4090 phillips) Indianapolis, IN, 46202-4108, United States. Electronic address: cphilli3@iupui.edu.
authors.forename: Carrie
authors.initials: C
authors.lastname: Phillips
authors.affiliation: El Camino Hospital, 2500 Grant Rd., St. GC33, Mountain View, CA, 94040, United States. Electronic address: asangoi2@yahoo.com.
authors.forename: Ankur R
authors.initials: AR
authors.lastname: Sangoi
authors.affiliation: Nephropath, 10810 Executive Center Drive, Suite 100, Little Rock, AR, 72211, United States. Electronic address: jon.wilson@nephropath.com.
authors.forename: Jon
authors.initials: J
authors.lastname: Wilson
authors.affiliation: William Beaumont Hospital, 3601 West 13 Mile Road Royal Oak, MI, 48073, United States. Electronic address: ping.zhang@beaumont.edu.
authors.forename: Ping L
authors.initials: PL
authors.lastname: Zhang
mesh_terms: D000328:Adult; D018207:Angiomyolipoma / Q000209:etiology*; D002292:Carcinoma, Renal Cell / Q000209:etiology / Q000378:metabolism; D002648:Child; D003560:Cysts / Q000209:etiology / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000209:etiology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014402:Tuberous Sclerosis / Q000150:complications / Q000175:diagnosis*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
keywords: Angiomyolipoma; Hamartin; Polycystic kidney disease; Renal cell carcinoma; Tuberin; Tuberous sclerosis complex