Role of CXCR4 and VEGF expression and metastatic locoregional lymphnodes in rectal carcinoma

Tatangelo F.*, Avallone A.**, Delrio P.°, Scala S.§, Botti G.*

•S.C. Anatomia Patologica ITN, Napoli** Oncologia Medica ,D.to Entero-proctologico ITN, Napoli° Oncologia Chirurgica, D.to Entero-proctologico ITN, Napoli§ Immunologia, ITN, Napoli

Introduction

Chemokine receptors are known to be involved in the lymphatic spread of many solid tumors, while VEGF is implicated in metastatic process.Their role in the prediction of lymphnode spread and distant metastasis in colorectal carcinoma could be of great importance for the selection of rectal carcinoma patients with worst prognosis.

Objectives

To evaluate the expression of CXCR4(receptor of

chemokine CXCL12) and VEGF(Vascular endothelial

Growth Factor) in rectal carcinoma and their relationship

with other biological and pathological parameters of

prognostic value

Materials and methods-1

N. 70 cases of stage II-III rectal carcinoma operated in

our institution from 2003-2007 were examined using

routine methods (e/e staining) and immunohistochemical

techniques for CXCR4, VEGF, p53 and TS106 detection,

on formalin fixed and paraffin embedded specimens.

Materials and methods-2

Multiple e/e stained sections of tumor and its related lymphnodes were examinedAll 70 patients were clinically R0 after surgery.Receptor expression (absent vs positive) of the overall tumor was related to other pathological parameters of prognostic value:-pT(according UICC)-grading-pN(according UICC)-lymphovascular invasion

Materials and methods-3

Antibodies used for immunohistochemical staining:

-anti CXCR4, clone 44716, R&D system, Minneapolis-anti VEGF, clone VG1, DAKO-anti TS106, ZYMED-anti p53, Novocastra

Results-1

Normal mucosa was not immunoreactive for

CXCR4,VEGF, TS106 and p53.

CXCR4 expression was + in 55 cases(78,5%)

VEGF expression was + in 43 cases(61, 4%)

TS106 expression was + in 65 cases(92,8%)

P53 expression was + in 68 cases(97,1%)

Results-2

Table 1 shows the correlation between CXCR4

and VEGF expression and some pathologic

parameters, as pT, Grading, pN and

lymphovascular invasion(LVI)

Table 1 - Correlation between CXCR4 and VEGF expression and other pathologic parameters

n. CXCR4 VEGF + - + -

pT 2 43 35 8 33 10pT3 27 20 7 10 17

G2 65 50 15 40 25G3 5 5 0 3 2

pN0 52 43 9 28 24pN1 15 9 6 13 2pN2 3 3 0 2 1

LVI – 48 33 15 23 25LVI + 22 22 0 20 2

Results-3

There is significant correlation between CXCR4 and VEGF expression and depth of invasion(pT), metastatic lymphnodes(pN) and LVI.

CXCR4 and VEGF expression was related to TS106 and p53 expression too

P 53 expression in neoplastic cells related to normal mucosa

TS106 expression in neoplastic cells

IIC staining for p53 and TS106 in rectal carcinoma

Strong cytoplasmic positivity of CXCR4

IIC staining for CXCR4 in rectal carcinoma

Cytoplasmic positivity of VEGF

IIC staining for VEGF in rectal carcinoma

Conclusion

Lymphnode status is related to lymphovascular invasion and to CXCR4, VEGF, TS106 and p53 expression.Notably, high expression of CXCR4 and VEGF was significantly associated with metastatic lymphnodal status and, then, with poor prognosis in rectal cancer patients.Further studies are necessary to clarify the real role of these molecules in invasive and metastatic process in rectal carcinoma.

References:

-Baggiolini M, Dewald B, Moser B, Human chemokines: an update, Annu Rev Immunol, 1997

-Maeda K, Yashiro M et al., Correlation between VEGF expression and lymphnode metastasis in carcinoma of the colon and rectum Surg today, 2003

-Yoshitake et al., Expression of SDF-1 and CXCR4 predicts lymphnode metastasis in crc BJC, 2008