The study is currently ongoing, the above being preliminary results
From these aspects, the conclusion would be that radiotherapy can have both positive (p53, MMP13, TIMP3) and negative (MMP1, TIMP1) implications on tumor behavior, normal epithelium and stroma, therefore , in order to be able to correlate these changes with a clear prognosis it would be necessary to study markers within the same group in which to monitor also the clinical evolution of patients. The objective would be a prospective study in : patient survival, disease-free range and perioperative morbidity correlated with immunohistochemistry
Tumor response to radiotherapy in rectal cancer.pptx
1. Tissue response to
radiotherapy in rectal cancer
(Ph D thesis conclusions, 2013)
Author: Sinziana Ionescu, general surgeon, PH D, Assistant professor,
Bucharest Oncology Institute Clinic I , Carol Davila University of
Medicine and Pharmacy , Bucharest , Romania
Coordinator : Prof dr Eugen Bratucu , PH D, Bucharest Oncology
Institute Clinic I , Carol Davila University of Medicine and Pharmacy ,
Bucharest , Romania
6. MMP1 expression after
radiotherapy
A B
C Fig.40.Expresia MMP1 în adenocarcinoamele
rectale după radioterapie (piese chirurgicale). A. Celulele tumorale sunt negative. B-
C. Pozitivitate citoplasmatică intensă în celulele tumorale. MMP1 x 200
a. Tumour cells are negative
b. -c. intense positivity of the
cytoplasm in the tumour cells
MMP1*200
9. The modification of the expression of MMP13 in the tumor
cells
a. Diminished positive cytoplasm and intense nuclear positivity for MMP13 of the
tumor cells in a rectal adenocarcinoma before radiotherapy
b. Positive cytoplasm and negative nucleus for MMP13 in the tumor cells after
radiotherapy
10. Variations of TIMP 1 with radiotherapy
RIB
RIC
0
5
10
15
20
25
30
0
pozitiv
0 pozitiv
RIB 9 20
RIC 3 26
Pre and postradic TIMP-1 at the level
of the tumour
chi=0.1508
p=0.0517
11. Pre-radiotherapy The expression tIMP1 in rectal adenocarcinomas before radiotherapy
(biopsies). A. Tumor cells are negative for TIMP1. B. Rare tumor cells with focal
cytoplasmic positivity for TIMP1. C. Intense cytoplasmic positivity for TIMP1 of tumor
cells. TIME1 x 400
Post-radiotherapy The expression tIMP1 in rectal adenocarcinomas after radiotherapy
(surgical parts). A-C. Intense cytoplasmic positivity in tumor cells. TIME1 x 400
12. RIB
RIC
0
5
10
15
20
25
0
pozitiv
0 pozitiv
RIB 8 21
RIC 21 8
TIMP-3 variation at the level of the tumor
chi=0.0029
P=0.00064
RIB
RIC
0
10
20
30
0
pozitiv
0 pozitiv
RIB 10 19
RIC 23 6
TIMP-3 la at the level of the tumor stroma
RIB
RIC
Chi=0.0026 P=0.0005
TIMP3 showed statistical variation in radiotherapy
This marker has been studied both at the tumor level (chi=0.0029, p=0.00064) and also
in the tumor stroma (chi=0.0026, p=0.0005), and in both cases it has shown statistical
relevance in terms of the response to radiotherapy.
13. The expression TIMP3 in rectal adenocarcinomas before radiotherapy
(biopsies). A. Tumor cells are negative for TIMP3. B. Low cytoplasmic and intense
nuclear positivity for TIMP3 of tumor cells; negative non-tumor mucosa. C. Intense
nuclear positivity for TIMP3 in tumor cells. TIMP3 x 400
The expression TIMP3 in rectal adenocarcinomas after radiotherapy (surgical
specimen ). A. The cytoplasm of tumor cells is negative for TIMP3. B. The cytoplasm
of tumor cells is/ focally weakly positive for TIMP3; tumour nuclei are negative. C. Rare
tumor nuclei positive for TIMP3. TIME3 x 400
14. Discussion and Conclusions
The groups of patients studied and the parameters studied within the thesis
were different as there was not enough clinical and paraclinical data The groups
of patients in whom immunohistochemical markers were studied showed a
number of 52 and 29 patients, respectively. In the second case, the group being
was at the lower limit of statistical relevance.
From the analysis of the group of 29 patients in which immunohistochemical markers
other than EGFR and VEGF were studied and their changes with radiotherapy, the
following markers showed significant variation:
P53 varied in expression, involving changes in cellular repair behavior in case of cellular
exposure to stress, in this case the "threat" of cellular injury being brought by radiotherapy
itself
MMP1 increased expression with radiotherapy, also with statistically relevant values and
since MMP1 is involved in the degradation of the extracellular matrix and in the
metastasis process, then immediate clinical involvement would be to be able to say if
radiotherapy does not increase the potential for metastasis of cells, through this
mechanism
15. MMP13 turned out negative (became from positive -»0) in most nuclei of tumor cells
in the tumor stroma, which would demonstrate an effect opposite to the previous one,
namely the involvement of radiotherapy in lowering the oncogenic potential
TIMP-1 can promote cell proliferation and in some cases even acquire anti-apoptotic
function; in our group, TIMP 1 has easily turned out positive with radiotherapy at the
tumor level, a result that is consistent with the results related to MMP-1
TIMP-3 turned out negative (most of the values became from positive-»0) with
statistical variation in both tumor and tumor stroma, and since the expression of this
gene was generally correlated with the multiplication response, then its decrease
with radiotherapy would lead to the conclusion that radiotherapy would inhibit tumor
cell proliferation through this mechanism
The study is currently ongoing, the above being preliminary results
From these aspects, the conclusion would be that radiotherapy can have both
positive (p53, MMP13, TIMP3) and negative (MMP1, TIMP1) implications on tumor
behavior, normal epithelium and stroma, therefore , in order to be able to correlate
these changes with a clear prognosis it would be necessary to study markers within
the same group in which to monitor also the clinical evolution of patients. The
objective would be a prospective study in : patient survival, disease-free range and
perioperative morbidity correlated with immunohistochemistry
16. Acknowledgements
The author would like to thank prof. dr. Zurac S. and prof. dr. Staniceanu F. from
the Colentina Clinical Hospital –Pathology department, Carol Davila University of
Medicine and Pharmacy , Bucharest , Romania for providing the histology and
immunohistochemistry data and constant support with the thesis and to prof. dr.
Bratucu E. for the interesting topic chosen and for the coordination and mentoring.
"ACKNOWLEDGEMENT: This paper is supported by the Sectoral Operational
Programme Human Resources Development (SOP HRD) 2007-2013, financed from
the European Social Fund and by the Romanian Government under the contract
number POSDRU/107/1.5/S/82839",
