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Proficient mismatch repair protein expression in Hodgkin and Reed Sternberg cells
Author(s) -
Re Daniel,
Benenson Lena,
Wickenhauser Claudia,
Starostik Petr,
StaratschekJox Andrea,
MüllerHermelink Hans Konrad,
Diehl Volker,
Wolf Jürgen
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1586
Subject(s) - microsatellite instability , reed–sternberg cell , dna mismatch repair , genome instability , loss of heterozygosity , biology , chromosome instability , microbiology and biotechnology , cancer research , germinal center , immunohistochemistry , gene , pathology , dna repair , genetics , allele , antibody , b cell , lymphoma , microsatellite , medicine , immunology , chromosome , dna damage , dna , hodgkin lymphoma
Hodgkin and Reed‐Sternberg (H/RS) cells are characterized by chromosomal instability. Nevertheless, neither specific nor consistent chromosomal alterations could be characterized in H/RS cells. Microsatellite instability (MSI) is another form of genomic instability but its role in the pathogenesis of classical Hodgkin's disease (cHD) has not been investigated so far. We analyzed MSI and mismatch repair (MMR) protein expression in H/RS cells of cHD in order to assess genomic instability in these cells. Using a sensitive single cell approach, MSI‐low was detected in a portion of single cells of the H/RS cell line L1236. Mutations of genes encoding for hMSH2 and hMLH1 were excluded by RT‐PCR in L1236 cells. An analysis of pooled single H/RS cells of seven primary cases of cHD showed loss of heterozygosity for some allelic markers but absence of MSI in all 7 cases. Owing to a tight correlation between MSI‐high, inactivating mutations of MMR genes and MMR protein expression in colon cancer, MMR protein expression commonly is used as a marker for MSI. In order to screen additional primary cases of cHD for MSI, we performed immunohistochemistry for hMSH2 and hMLH1 in 6 of the 7 cases analyzed by single cell PCR and 20 additional cases of cHD. H/RS cells from 25 out of 26 cases showed a nuclear staining pattern for hMSH2 and hMLH1 similar to germinal center B cells of non‐malignant lymph nodes. These results indicate a proficient MMR system in most H/RS cells. It is concluded that a defect MMR system is unlikely to contribute to the malignant phenotype and genomic instability of H/RS cells in cHD. © 2002 Wiley‐Liss, Inc.