| Abstract |
Data from laboratory and clinical studies have shown the presence of intracellular pathways such as Ras / Raf-1 / ERK1 / 2, in breast carcer. However, the interactions between these intracellular pathways and specific cellular receptors as well as the relation of these pathways with molecules associated with tumor cell proliferation are not fully understood.
The main purpose of this study was to clarify the correlations that exist between cellular receptor molecules, intracellular signaling pathways and their target molecules like pElk-1 and others such as Cyclin D1 and Ki-67 that play an important role in the transition of cells from the G1 to the S phase. Further objective of this study was to investigate the relationship between these molecules with breast tumors’ pathological characteristics, their proliferative activity, their ability to metastasize and finally with patients'survival.
One hundred and seventy (n = 170) of female operable breast cancer cases were studied for the expression of the ERa, ERb, PR, Her-2, receptor and the expression of intracellular molecules ERK1 / 2, pElk-1, CyclinD1 and Ki6 using immunohistochemistry 7.
This study was the first to demonstrate increased expression of the phosphorylated form of the protein Elk-1 (pElk-1) in tissue samples from human breast cancer using immunohistochemistry. We fουnd a statistically significanτ relationship between the expression of estrogen receptors ERa with pElk-1 and Cyclin D1 and between pElk-1 and Cyclin D1, as well. There was also a statistically significant correlation between the expression of ERK1 / 2 and pELk-1, but we did not find any other relationship between ERK1 / 2 and the other molecules. We have also found a positive correlation between the expression of ER and PR and a negative relation of their expression with HER-2. The mean overall survival was increased among patients with positive tumors for p Elk-1 and ERK1/2 although not statistically significant.
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The expression of pElk-1 and Cyclin D1 in Basal cell carcinomas was reduced. We have noticed an increase of the expression of Cyclin D1 in Luminal B HER-2 negative breast carcinomas. Although not statistically significant, there was increased expression of pElk-1 in Luminal A and Luminal B HER-2 negative breast carcinomas. The median value for the pElk-1 was significantly higher compared to its expression in Basal and HER-2 tumors. It is also important to stress that H-score for pElk-1 was higher in Luminal A and Luminal B / Her-2 negative tumors compared to the Luminal B / Her-2 positive, HER-2 and Basal cell carcinomas.
Our findings offer a new perspective for the role of ERK1/2 and pElk-1 in breast neoplasia suggesting a direct relation for pElk-1 molecule to tumor biology and a putative target of personalized breast cancer therapies, although its prognostic/discriminant role is not supported.
Further studies of ER, PR, HER-2 expression in relation to the Raf-1 / MEK-1 / ERK1 / 2 pathway as well as to the p Elk-1, CyclinD1 and Ki-67 expression in combination with other intracellular signalling pathways and cellular receptors will provide more information regarding cellular proliferation and survival. Finally, further studies with larger number of patients and longer follow-up periods will provide more accurate information for the role of the above molecules as potential prognostic markers.
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Οδοί ενεργοποίησης του κυτταρικού πολλαπλασιασμού στα καρκινώματα του μαστού : Σχέση με το κλινικοπαθολογοανατομικό στάδιο της νόσου
