Microsatellite instability and immunostaining for MSH-2 and MLH-1 in cutaneous and internal tumors from patients with the Muir-Torre syndrome.
BACKGROUND
Muir-Torre syndrome (MTS) is characterized by the co-existence of sebaceous gland tumors of the skin and internal malignancies. Currently, MTS is regarded as a variant of the hereditary non-polyposis colon cancer syndrome (HNPCC). Both MTS and HNPCC are secondary to germline mutations in DNA mismatch repair genes (mainly MSH-2 and MLH-1).


METHODS
Cutaneous (eight sebaceous adenomas, one sebaceous carcinoma and one keratoacanthoma) and internal tumors (four colonic adenocarcinomas, two endometrial carcinomas, two transitional cell carcinomas of renal pelvis and ureter, one adenocarcinoma of the small bowel, one ovarian carcinoma and one colonic tubular adenoma) were obtained from six patients with MTS and were subjected to microsatellite instability (MI) analysis, and to immunostaining for MLH-1 and MSH-2. MI was assessed by evaluating three (CA)n dinucleotide repeats (D2S123, D5S346, D17S250) and the mononucleotide tracts BAT 26 and BAT 25.


RESULTS
All cutaneous and internal tumors exhibited MI. An immunohistochemical concordance between all tumors within each single patient was obtained in five cases. In these five patients all tumors exhibited a lack of MSH-2 staining, consistent with a germline abnormality in this gene. In the one remaining case, the immunohistochemical staining in the sebaceous adenoma was negative for MLH-1 and positive for MSH-2, consistent with a germline alteration in MLH-1. However, the colonic adenocarcinoma in that patient showed positivity for MSH-2 and an equivocal positivity for MLH-1.


CONCLUSIONS
The results confirm that tumors from patients with MTS exhibit MI. Moreover, immunostaining for MLH-1 and MSH-2 may be useful to identify the most probable gene responsible for the disease in each family.
Machin
Pilar
P
Department of Pathology, Hospital de la Santa Creu i Sant Pau, Avda Sant Antoni Maria Claret 167, 08025 Barcelona, Spain.
Catasus
Lluis
L
Pons
Cristina
C
Muñoz
Josefina
J
Conde-Zurita
Jose Maria
JM
Balmaña
Judith
J
Barnadas
Maria
M
Martí
Rosa M
RM
Prat
Jaime
J
Matias-Guiu
Xavier
X
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D018895:Microsatellite Repeats / Q000235:genetics*; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins; D012626:Sebaceous Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D005819:Genetic Markers; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein