IMMUNOHISTOCHEMICAL
ANALYSIS
OF
PREDICTIVE
FACTORS RESPONSE TO NEOADJUVANT THERAPY IN
RECTAL CANCER
ABSTRACT
 INTRODUCTION
The rectal cancer is a malignant tumor that accounts for 30-35% of all cancers of the
large intestine, which in turn represents the 10% of all cancers. Originates from the
cells of the mucosa but frequently represents the malignant transformation of his
most precancerous common lesion that is polyp. In some cases, the cancer originates
primarily from the rectal mucosa, without evidence of pre-existing polyps.
Despite the radical surgical resection remains the main option for the treatment of
rectal cancer, the percentage of local recurrence of between 30 and 70%. In the last
decade, the therapeutic approach has gradually changed with the increasingly
frequent recourse to neoadjuvant therapy as a tratment of choice locally advanced
cancer (T3-T4) with or without lymphonodal metastases.
The pre-operative radiochemotherapy offers many potential benefits: reducing the
acute toxicity avoiding the irradiation of the neorectum and increases the
effectiveness of te dose, radiatine tissues well oxygenated.
This type of therapeutic approach also improves the resection through downstaging of
cancer, increases the possibilità of maintaining the funcionality of the sphincters and
allows a regression of vaious degree of malignancy.
The aim of our analysis was to assess the pathological response, as tumor regression
and staging of rectal cancers
treated with neoadjuvant therapy and to identify
histopathological and immunohistochemical factors predictive of survival.
 MATERIALS AND METHODS
The study includes 73 patients who had presented the diagnosis with rectal cancer
and were treated with neoadjuvant therapy durino the period between 2003 and 2007
and analyzed at the Institute of Pathology of Polytechnical University of Marche. In
all cases the diagnosis infiltrating adenocarcinoma was established by histogical
examination of rectal biopses.
Then patients were staged in accordance with the guidelines of TNM.
All patients were undergoing radiotherapy. In 61 cases was associated chemotherapy.
In all cases was performed immunohistochemical evaluation of NF-kB, Survivin, Ki67, P53 and Bcl-2.
The immunohistochemical samples thus obtained were valued amount and the result
was expressed as a perctage of neoplastic cells tested positive for colorino.
The kind of positività is different depending suspected og antigen.
 RESULTS
The study includes 73 cases rectal adenocarcinoma treated with neoadjuvant therapy,
came out of the Institute of Pathology of Polytechnical University of Marche between
2003 and 2007. The average age at diagnosis was 66 years, with minimum of 36
years and maximum of 85. Of 73 cases, 47 (64%) were males (M) and 26 (36%)
female (F), with a M/F of 1/8.
Patients undergoing radiotherapy combined with chemotherapy were 61 (83%), while
12 (17%) have played only radiotherapy because of co-morbodity.
Histological examination the infiltrating tumors were adenocarcinoma (NOS) in 59
cases (97%) and adenocarcinoma mucinous in 2 cases (3%). The NOS
adenocarcinomas were well differentiated (G1) in 37 cases (63%) and little different
in 1 case (1%).
Immunohistochemistry:
- NF-kB: the valuation of expression of NF-kB was possibile in 59 cases: 52
(88%) were negative and 7 ( 12%) positive (cut-off of positività = 10%). In the
group of patients who have run radiochemotherapy, the positività of NF-kB
was present in 6 cases (12%) and 42 cases (88%) were negative.
- P53: the valuation of expression of P53 was possibile in 58 cases: 40 (68%)
expressing immunohistochemistry was equal to greater than 10%, while in 18
cases (31%) was lower.
- Bcl-2: the expression of Bcl-2 was evaluated in 58 cases; 50 tumors (86%) had
lower expression of 10%, while 8 cases (14%) were positive in at least 10% of
neoplastic cells.
- Survivin: the expression of nuclear survivin was evaluated in 57 tumors. In 16
(28%), more than 10% of neoplastic cells were positive, while 41 cases (72%)
were negative.
- Ki-67: the proliferative index was calculated in 58 cases and we obtained an
avarege of 51.4+- 33.6 DS, with a minimum of 0 and a maximum of 100. The
9 cases with proliferative index equal to zero all showed obvious changes
cytological kind of regressivE.
 CONCLUSIONI
In our study we investigated by immunohistochemical technique if the scorse of
NF-kB, Survivin, Bcl2, P53 and Ki-67 on the sample post-surgical treatment has a
prognostic significance. Statistical analysis none of these biological markers was
significant both for DSS (disease-specific suvival) for the DFS (disease-free
survival). But selecting the group of patients who also received pre-operative
chemotherapy, the positività of residual cancer to NF-kB becomes a negative
prognostic factor (p=0.01) for DSS.
Our study also showed a good pathological response of rectal cancer neoadjuvant
therapy and identified some important factors to predict disease prognosis and
then determine the strategy for adjuvant therapy.
These factors are the stages ypN (precence and number of lymphnode metastases),
ypM (precence and number of distant metastases), and the CRM (study of
circumferential margin) and the NF-kB, for the DSS and the stage ypT (infiltration
of the wall), ypN and CRM for the DSF.