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  • 1
    ISSN: 1573-7217
    Keywords: breast cancer ; mdr1 ; neoadjuvant chemotherapy and hormone therapy ; P-glycoprotein ; multi-drug resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract mdr1 expression by reverse transcription and polymerase chain reaction(RT-PCR) has been compared to P-glycoprotein (Pgp) expression byimmunohistochemistry (IHC) and correlated with clinical response toneoadjuvant therapy. RNA has been recovered from glass slide smears offine-needle aspiration from 57 untreated primary breast cancers prior toneoadjuvant chemotherapy (33 cases), hormone therapy (23 cases), or both (1case). Furthermore, mdr1 mRNA has been analyzed in 6 cases after 2 months oftreatment. The neoadjuvant therapy consisted of 4 cycles of adriamycin andcyclophosphamide or tamoxifen. Of 57 tumor specimens, an interpretableresult was obtained in 52 cases, indicating the feasibility of the analysisby RT-PCR with very small tumor specimens. The presence of mdr1 mRNA hasbeen documented in 44/52 (84%) tumor samples with a spectrum ofexpression levels. The expression of mdr1 mRNA was compared withP-glycoprotein (Pgp) expression by IHC using JSB-1, 4E3, and C494 monoclonalantibodies in 48 of the 52 interpretable tumor samples. 12/48 (25%)expressed Pgp by IHC. All tumors expressing Pgp by IHC were also positive byRT-PCR. The results confirm the higher prevalence of mdr1 mRNA compared tothe protein expression. However, mdr1 mRNA expression was found to correlatesignificantly with resistance to neoadjuvant hormone therapy only while Pgpexpression detected by JSB-1 immunostaining only correlated withchemoresistance. The lack of convincing correlation with chemoresistancesuggests that mRNA and Pgp may not be directly or solely responsible forclinical response to drugs. Further studies should focus on theposttranslational modulation of P-glycoprotein and other mechanisms of drugresistance.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7217
    Keywords: breast cancer ; cathepsin D ; immunohistochemistry ; protease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was aimed at investigating the influence of cathepsin D (CD) expression by cancer cells and stromal cells on breast cancer prognosis. This is a study of 1348 node‐positive (NPBC) and node‐negative (NNBC) breast cancers diagnosed between 1980 and 1986 and with a minimum follow‐up of 5.2 years. CD expression was assessed by immunohistochemistry on archival material using a polyclonal antibody. The expression by cancer and stromal cells was assessed separately and correlated with distant metastasis free (DMFS) and overall survival (OS). Cancer cells expressed CD (more than 10% cells expressing CD) in 38.9% of cases and reactive stromal cells in 43.6%. CD expression by reactive stromal cells, and not cancer cells, correlated with several factors of poor prognosis by cancer cells. A strong association was also found with expression of other proteases (stromelysin‐3, gelatinase A, and urokinase Plasminogen Activator) by these same reactive stromal cells. CD expression by cancer cells did not predict DMFS or OS but, by univariate analysis, CD expression by reactive stromal cells was associated with earlier recurrence and shorter survival in NNBC (p = 0.0425) and NPBC patients submitted to adjuvant chemotherapy (p = 0.0234). However, CD expression by reactive stromal cells remained a significant predictor of recurrence by multivariate analyses only in a subgroup of NPBC submitted to adjuvant chemotherapy. Overall, those data support the concept that proteases produced by reactive stromal cells are under cancer cell stimulation and that CD by stromal cells, and not cancer cells, influences the prognosis, but only in a subgroup of patients with breast cancer.
    Type of Medium: Electronic Resource
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