Papillary lesions of the breast: a molecular progression?
BACKGROUND
Breast papillary lesions represent a heterogeneous group of tumors ranging from benign to malignant, including several intermediate forms. Malignant papillary tumors are rare and their molecular characterization is still limited. A few studies pointed to the presence of specific genetic alterations that could be relevant both for diagnostic purposes and to elucidate tumour development and progression. In order to look into the issue, we compared LOH relative frequencies of four microsatellite markers located on chromosome 16 in a set of morphologically different papillary breast lesions. LOH at TP53 locus was also analyzed throughout lesions.


METHODS
Fifteen cases were analyzed. Sections including a malignant papillary lesion, a benign lesion (when available), and normal breast tissue were selected. Fifteen malignant and twelve benign areas were microdissected using the Leica laser microdissection system (AS LMD). After DNA extraction samples were tested for the following markers: TP53, D16S423, D16S310, DS163210 and D16S476, and analyzed on ABI PRISM 3100 (Applied Biosystems, Foster city CA).


RESULTS
Fourteen malignant lesions and twelve paired benign areas appeared to be informative for at least one of the four markers on chromosome 16. In particular, LOH at loci 16p13 and 16q21 was detected in both benign and malignant lesions, whereas LOH at locus 16q23 was limited to malignant lesions. Nine malignant and seven benign lesions were informative for LOH at TP53 locus, that was found to be significantly associated (p=0.01) with the malignant phenotype.


CONCLUSIONS
Our data suggest an involvement of chromosome 16 mutations in the early steps of breast papillary tumorigenesis. TP53 deletion and possibly LOH at 16q23 appear to play a role as progression factors, being they significantly associated with malignant transformation of breast papilloma.
Di Cristofano
Claudio
C
Division of Surgical, Molecular and Ultrastructural Pathology, University of Pisa and University Hospital of Pisa, Italy.
Mrad
Karima
K
Zavaglia
Katia
K
Bertacca
Gloria
G
Aretini
Paolo
P
Cipollini
Giovanna
G
Bevilacqua
Generoso
G
Ben Romdhane
Kaled
K
Cavazzana
Andrea
A
D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics; D002291:Carcinoma, Papillary / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D018300:Papilloma, Intraductal / Q000235:genetics*; D018709:Statistics, Nonparametric
D014408:Biomarkers, Tumor