Unusual tumors associated with the hereditary nonpolyposis colorectal cancer syndrome.
The molecular pathogenesis of tumors outside the usual tumor spectrum for hereditary nonpolyposis colorectal cancer (HNPCC) is currently controversial. Specifically, it is not known whether these tumors are related to defects in DNA mismatch repair or arise independently of this defect in these patients. Here, we report two young patients, each with a known MSH2 mutation in the family, who developed rare tumors (adrenal cortical carcinoma and anaplastic carcinoma of the thyroid) that are not usually associated with HNPCC. Both of these patients were members of families that fulfilled modified Amsterdam (Amsterdam II) criteria for this familial cancer syndrome. Both the adrenal tumor and the thyroid tumor showed complete loss of immunohistochemical expression for MSH2 protein. Neither tumor was considered microsatellite instability-high following microsatellite instability analysis using the established National Cancer Institute panel of five microsatellite markers. To our knowledge, MSH2 defects in these types of tumors have not been previously reported in patients with the HNPCC syndrome. Our results suggest that microsatellite instability analysis using the National Cancer Institute panel of five microsatellite markers may not detect microsatellite instability in tumors that fall outside the usual tumor spectrum of this syndrome. Therefore, when analyzing unusual tumors in patients with known or suspected HNPCC syndrome, we advocate the performance of immunohistochemistry for mismatch repair gene products in addition to microsatellite instability analysis.
Broaddus
Russell R
RR
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. rbroaddus@mdanderson.org
Lynch
Patrick M
PM
Lu
Karen H
KH
Luthra
Raja
R
Michelson
Sara J
SJ
D048868:Adaptor Proteins, Signal Transducing; D000306:Adrenal Cortex Neoplasms / Q000150:complications* / Q000473:pathology; D000328:Adult; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D013577:Syndrome; D013964:Thyroid Neoplasms / Q000150:complications* / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; 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