Phenotypic changes of p53, HER2, and FAS system in multiple normal tissues surrounding breast cancer.
To determine whether phenotypic field changes occur in tissues adjacent to carcinoma, we assayed, by immunohistochemistry, the expression of HER-2, p53, Fas, and FasL in 72 breast cancers (BC) and multiple autologous peritumoral tissues (PTTs) sampled up to 5 cm distance and in 44 benign breast tumors (BBTs). About 5% and 3% of the PTTs and 4.5% and 6.8% of BBTs showed alterations in HER2 and p53 expression, respectively. Of interest, gene amplification was observed in 50% of HER2 positive PTTs, but not in any HER2 positive BBTs. Fas, highly expressed in BBTs and downregulated in BC, maintained its expression in PTTs, whereas FasL, usually negative in BBTs, was upregulated in BC as well as in the PTTs closest (1 cm) to the invasive lesion. Our data suggest that FasL could be a potential novel biomarker of transformation, which may identify, along with HER2 and p53, precursor lesions in a genetically altered breast tissue.
Mottolese
Marcella
M
Department of Pathology, Regina Elena Cancer Institute, Rome, Italy.
Nádasi
Edit A
EA
Botti
Claudio
C
Cianciulli
Anna M
AM
Merola
Roberta
R
Buglioni
Simonetta
S
Benevolo
Maria
M
Giannarelli
Diana
D
Marandino
Ferdinando
F
Donnorso
Raffaele Perrone
RP
Venturo
Irene
I
Natali
Pier Giorgio
PG
D014408:Biomarkers, Tumor / Q000378:metabolism; D001940:Breast / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D001941:Breast Diseases / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D042241:Early Diagnosis; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
D014408:Biomarkers, Tumor; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; C505661:FASLG protein, human