Methylation biomarkers for pleomorphic lobular breast cancer - a short report

Cathy B Moelans,Peter Bult,Horst Buerger,Paul J Van Diest,Gabor Cserni,Eva J Vlug,Cigdem Ercan,Patrick W B Derksen

doi:10.1007/s13402-015-0241-9

Abstract

BackgroundPleomorphic invasive lobular cancer (pleomorphic ILC) is a rare variant of ILC that is characterized by a classic ILC-like growth pattern combined with an infiltrative ductal cancer (IDC)-like high nuclear atypicality. There is an ongoing discussion whether pleomorphic ILC is a dedifferentiated form of ILC or in origin an IDC with a secondary loss of cohesion. Since gene promoter hypermethylation is an early event in breast carcinogenesis and thus may provide information on tumor progression, we set out to compare the methylation patterns of pleomorphic ILC, classic ILC and IDC. In addition, we aimed at analyzing the methylation status of pleomorphic ILC.MethodsWe performed promoter methylation profiling of 24 established and putative tumor suppressor genes by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) analysis in 20 classical ILC, 16 pleomorphic ILC and 20 IDC cases.ResultsWe found that pleomorphic ILC showed relatively low TP73 and MLH1 methylation levels and relatively high RASSF1A methylation levels compared to classic ILC. Compared to IDC, pleomorphic ILC showed relatively low MLH1 and BRCA1 methylation levels. Hierarchical cluster analysis revealed a similar methylation pattern for pleomorphic ILC and IDC, while the methylation pattern of classic ILC was different.ConclusionThis is the first report to identify TP73, RASSF1A, MLH1 and BRCA1 as possible biomarkers to distinguish pleomorphic ILC from classic ILC and IDC.

Highlights

Invasive lobular breast cancer (ILC) is the second most prevalent histological breast cancer type that accounts for 10–15 % of all breast cancers [1, 2]
Pleomorphic ILC tumors have been reported to be significantly larger than classic ILC tumors, and pleomorphic ILC patients often present with lymph node involvement and a higher rate of metastatic disease compared to classical ILC [9]
We found that the methylation patterns of classic ILC and infiltrative ductal cancer (IDC) were comparable, and that the classic ILC and IDC profiles were mildly different from pleomorphic ILC

Summary

Results

RASSF1A methylation levels compared to classic ILC. Compared to IDC, pleomorphic ILC showed relatively low MLH1 and BRCA1 methylation levels. Hierarchical cluster analysis revealed a similar methylation pattern for pleomorphic ILC and IDC, while the methylation pattern of classic ILC was different

Conclusion

Introduction

Patient material

Methylation-specific multiplex ligation-dependent probe amplification

Statistics

Results and discussion