Poor prognosis in breast carcinomas correlates with increased expression of targetable CD146 and c-Met and with proteomic basal-like phenotype.
Genomic studies have led to new taxonomic classifications of breast carcinomas. Proteomic investigations using tissue microarrays have yielded complementary results and are useful in identifying potential molecular targets for specific therapies. Searching for new drug targets is particularly important for tumors of poor prognosis, such as breast tumors that lack estrogen receptors and HER2 amplification; in these tumors, certain molecules probably play a significant role in tumor spreading through the stromal microvasculature. We investigated 930 breast carcinomas categorized according to patients' survival (range of follow-up = 4-10 years; median follow-up = 6.5 years) using (1) automated immunohistochemical procedures (Ventana, Cedex, France) with tissue microarrays (Alphelys, Plaisir, France) and (2) quantification of immunoprecipitates assessed by automated image analysis densitometry (SAMBA, Meylan, France). Expression of c-Met and CD146 and that of signaling transducers PI3K, FAK, and FYN were compared in living and deceased patients. Expression of some proteins recently reported to be characteristic of basal cell carcinomas was also assessed, namely, CK5-6, caveolin-1, carbonic anhydrase IX, p63, and CD117; these also constitute potential targets for therapies for aggressive tumors. Overexpression of these proteins was observed in deceased or metastatic patients (P < .01 to P < .00001), particularly node-negative patients (except for FYN, p63, and CD146). c-Met and CD146 are involved in tumor spreading, and our results suggest that they probably play an important role in patients' death, along with other proteins involved in hypoxia (carbonic anhydrase IX) and other cell functions or structures (caveolin-1, CD117, CK5-6, and p63) that are expressed in an aggressive subtype of basal cell carcinoma for which no specific therapy is available.
Garcia
Stéphane
S
Department of Pathology, Centre Hospitalo-Universitaire Nord, 13916 Marseille, France.
Dalès
Jean-Philippe
JP
Charafe-Jauffret
Emmanuelle
E
Carpentier-Meunier
Séverine
S
Andrac-Meyer
Lucile
L
Jacquemier
Jocelyne
J
Andonian
Claudine
C
Lavaut
Marie-Noëlle
MN
Allasia
Claude
C
Bonnier
Pascal
P
Charpin
Colette
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D051929:CD146 Antigen / Q000096:biosynthesis*; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000096:biosynthesis; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008875:Middle Aged; D018295:Neoplasms, Basal Cell / Q000378:metabolism*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis; D011379:Prognosis; D040901:Proteomics; D051076:Proto-Oncogene Proteins c-fyn / Q000096:biosynthesis; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis*; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D051929:CD146 Antigen; D019869:Phosphatidylinositol 3-Kinases; D019859:Proto-Oncogene Proteins c-met; C494957:FYN protein, human; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051076:Proto-Oncogene Proteins c-fyn