Περιεγχειρητική κινητική αγγειορυθμιστικών παραγόντων σε ασθενείς με καρκίνο του μαστού

Abstract

Βackground: angiogenesis is seen during the multiple stages of carcinogenesis, aswell as during the process of surgical wound healing, a fact which has led tosubstantial debate over the last decades about the potential impact of surgery upon thefinal outcome of ceratin patients treated for breast cancer.Aim: the present research aims at investigating the potential effect of surgery on theprocess of angiogenesis, by studying a number of factors that are related to the latter,in patients suffering from breast cancer before and after the time of the procedure,whilst comparing these results with those of patients that were operated on their breastfor non-malignant disease.Material-Methods: blood from 10 female patients with breast adenocarcinoma(Study Group) was collected via venipuncture before surgery (labeled as PRO), aswell as on post-operative day 3 (labeled as D3) and day 7 (labeled as D7). Moreover,blood samples were also taken from 6 female patients with fibroadenoma (ControlGroup) before surgery (PRO) and on day 3 afetr surgery (D3). These samples weremeasured for detection of circulating levels of three established angiogenesisbiomarkers using ELISA (Enzyme-Linked ImmunoSorbent Assay): VascularEndothelial Growth Factor-A (VEFG-A), Interleukin-8 (IL-8) and basic FibroblastGrowth factor (bFGF or FGF-2). In addition, circulating transcripts of 84 agiogenesirelatedgenes were determined using RT-PCR (Real Time Polymerase ChainReaction). The two groups of patients were firstly compared to each other regardingtheir results. Also, patients belonging to the Study Group were analized at differenttime points regarding surgery. Finally, the results were investigated againstclinicopathological data and patient outcome.Results: using ELISA we were able to detect increased levels of circulating VEGF-Aand IL-8 in the Study Group patients compared to the Control Group patientspreoperatively (p=0,0381 and p=0,0218 respectively), while for bFGF there was nostatistically significant difference documented. Surgery resulted in a significantincrease in VEGF-A levels on D3 (p=0,0389) and D7 (p=0,0172) as compared toPRO levels. Perioperative kinetics of IL-8 showed a mild trend towards increase,which, however, was not statistically significant. Postoperative levels of bFGF wereslightly increased on D3, but on D7 they were even lower than preoperative values(p=0,0205). Using RT-PCR certain differences between the Study Group and theControl Group were recorded regarding the circulating transcripts of a great numberof angiogenesis-related genes preoperatively: upregulation of VEGF-C, EGF, IL-8,FGF-1, SPHK1, NRP1, LAMA5, COL4A3, TEK, EFNA3, EFNB2. AKT1, ITGB3,THBS1, CCL11, TIMP3 and downregulation of CXCL10. Moreover, mastectomyinduced an altered expression in several key-genes in breast cancer patients:upregulation of THBS1, COL4A3, BAI1, ITGB3 and downregulation of EREG,SERPIFN1, CXCL9, CXCL10, IL1B, CCL2, CXCL1, HIF1A, NOTCH4. Conclusions: patients suffering from breast cancer have a different angiogenic profilein comparison to patients with fibroadenoma, as documented through their differencesin circulating levels of angiogenic factors. These levels are greatly changed after thesurgical procedure. VEGF showed a transient increase, while bFGF initially increasedbut only to finally decrease to levels that were even lower than the preoperative ones.Moreover, mastectomy promoted a shift in the expression pattern of a broad panel ofangiogenesis-related gene transcripts.