Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Alevizopoulos Nektarios
Dissertation committee:
Αθανάσιος Αρμακόλας, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αντώνιος Χατζηγεωργίου, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αναστάσιος Φιλίππου, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Σταμάτης Θεοχάρης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ανδρέας Χρ Λάζαρης,Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Χαρίκλεια Γακιοπούλου, Καθηγήτρια , Ιατρική Σχολή, ΕΚΠΑ
Αφροδίτη Νόννη, Καθηγήτρια , Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Η έκφραση του Ec πεπτιδίου της ισομορφής IGF 1Ec στον καρκίνο του προστάτη
Translated title:
Ec peptide expression of isomorf IGF 1 E c in prostate cancer
Summary:
Introduction and Objectives
Prostate cancer (PCa) is the second most commonly diagnosed cancer in men. In
contrast to localized low grade disease, locally advanced and metastatic PCa leads
to increased mortality. Insulin-like growth factor 1 (IGF-1) is a growth factor that
regulates the development of striated muscle. Recent evidence suggests a role for
the insulin-like growth factor-1Ec (IGF-IEc) transcript variant in cancer biology.
The aim of the present study is to investigate whether IGF-IEc expression is
associated with prostate cancer histologic parameters, in order to involve in the
treatment new therapeutic targeted approaches.
Materials and Methods
Archive material from radical prostatectomy specimens of patients naïve to androgen
blockade or other hormone therapy were reviewed. Two groups of patients were
selected: Group A: 50 patients with prostatic adenocarcinoma Grade Group 1 or 2
(Gleason Score 6 or Gleason Score 7 with pattern 3 >90%) and Group B: 50 patients
with prostatic adenocarcinoma Grade Group 5 (Gleason Score 9 or Gleason Score
10). This was followed by re-evaluation of the histological slides and selection of
representative ones. Then the corresponding paraffin blocks were selected.
Monoclonal antibody against IGF1Ec was standardized in sections of striated muscle
tissue and other tissues as well as in benign and malignant prostatic tissue.
Sections were cut from the corresponding paraffin blocks on super frost slides.
Immunohistochemistry was performed on a Ventana BenchMark ULTRA platform
using a monoclonal antibody against IGF1Ec at a dilution of 1:50. Mainly striated
muscle and liver tissue were used as positive control. Sections without the
application of the primary antibody were used as negative controls. This was
followed by a microscopic study of the material. Cytoplasmic granular expression of
the antibody was observed and graded as grade 1 (weak intensity), grade 2
(moderate intensity) and grade 3 (strong intensity).
The H scoring system was applied, which integrates the extent and the intensity of
the immunostaining (semiquantitative analysis of protein immunoexpression).
Specifically, the percentage of positive cells was measured in each section and
multiplied by 1, 2 and 3, respectively (score 1= percentage with grade 1 intensity x 1;
score 2= percentage with grade 2 intensity x 2; score 3= percentage with grade 3
intensity X 3). A total score between 0 and 300 was calculated for each case (total
score = score 1 + score 2 + score 3).
Results
Normal prostate epithelium was negative or demonstrated mild IGF-IEc cytoplasmic
expression, whereas prostate cancer exhibited mild to strong cytoplasmic
immunoexpression.
A statistically significant positive correlation (p<0,05) of IGF1Ec immunoexpression
with histological parameters (Gleason score, Grade group, cribriform pattern,
extraprostatic extension, tumor volume, surgical margins, seminal vesicles invasion
and pelvic lymph node metastasis) was observed.
Furthermore there was a statistically significant difference (p<0,05) between IGF1Ec
immunoexpression in low (Group A) and high grade carcinoma (Group B)
[statistically significant higher expression in Group B].
Conclusions
The present data demonstrate that IGF-IEc is highly expressed in GG 5 locally
advanced prostate cancer and therefore could be a promising targeted approach in
the therapeutic panel.
Main subject category:
Health Sciences
Keywords:
Prostate cancer, Ec Peptide,Insulin growth factor,Prostate cancer biology,Monoclonal targeted antibodies of prostate cancer
Number of references:
175
