Shtabinskaya T.T.*, Bodnar M.**, Lyalikov S.A.*, Basinsky V.A.*, Marshalek A.**
The role of the level of angiogenesis markers expression in prognosticating the effectiveness of postoperative chemotherapy for colorectal cancer
*Educational Establishment «Grodno State Medical University», Grodno, Republic of Belarus
**Collegium Medicum in Bydgoshch, the University named after N.Kopernik, Poland
Vestnik VGMU. 2015;14(6):84-92.
Objectives. To determine the value of the expression level of some markers of angiogenesis in the prediction of the effectiveness of postoperative adjuvant chemotherapy for colorectal cancer.
Material and methods. The clinical and morphological analysis of 72 cases of colorectal cancer removed in the period from 2001 to 2011 in Grodno Regional Oncology Center (Belarus) was made. The investigated cases were divided into 2 groups. The first group included 22 patients treated with chemotherapy after the resection of the colon with tumor. The second group consisted of 50 patients without chemotherapy. Immunohistochemical study was performed in the laboratory of Collegium Medicum in Bydgoshch (Poland) using mice monoclonal antibodies to MMP-2, VEGF, CD 105, rabbits polyclonal antibodies to Erk2, iNOS, NRP1, TGF-s, MMP-9. The expression of markers was quantified by means of the computer program Aperio Image Scope_v126.96.36.1997. The statistical analysis was made using STATISTICA 10.0 (SNAXAR207F394425FA-Q). The construction of multifactor model of the prediction of three- and five-year outcome was performed using discriminant analysis.
Results. 1) The dependence between the level of total positivity of TGF-R, MMP 2,9, iNOS, NRP1, Erk2 and the survival of patients who have undergone postoperative chemotherapy has not been detected; 2) the reliably high level of CD105 positivity is detected in the group of patients with the survival rate of less than 3 (p=0,002) and 5 years (p=0,038) and total VEGF positivity was significantly higher in the group with the survival rate of more than 3 years (p=0,05); 3) high level of positivity of VEGF in the tumor stroma, low Erk2 positivity in tumor cells and low expression of CD105 are associated with good effect of chemotherapy and the survival over 3 years; 4) low levels of CD 105 positivity, Erk2 in tumor cells and MMP-9 in the tumor stroma are associated with good effect of chemotherapy and the survival over 5 years.
Conclusions. The constructed models can be used in the clinical practice for the prognostication of the effectiveness of postoperative chemotherapy for colorectal cancer.
Key words: colorectal cancer, angiogenesis, postoperative chemotherapy, prognosis.
1. Brusina EB, Magarill YuA, Kutikhin AG. Epidemiologiia raka [Cancer epidemiology]: ucheb posobie dlia poslediplom podgot spetsialistov. Kemerovo, RF: KemGMA; 2011. 179 р.
2. Voqel I, Soeth E, Roder C, Kremer B, Henne-Bruns D, Kalthoff H. Disseminated tumor cells in the blood and/or bone marrow of patients with colorectal carcinoma are an independent prognostic factor. Ann Oncol. 2000;11(suppl 4):43.
3. Moiseenko VM, Orlova RV. Ad"iuvantnoe lechenie bol'nykh rakom obodochnoi kishki [Adjyuvantny treatment of patients with cancer of a colonic intestine]. Prakt Onkologiia. 2000;(1):19-23.
4. Rougier P. Palliative and adjuvant chemotherapy in colorectal cancer. Eur J Cancer. 2001 Oct;37 Suppl 7:S189-202.
5. Haller DG. New Approaches to Adjuvant Therapy for Colorectal Cancer. In: Third International Conference Perspectives in Colorectal Cancer, a consensus meeting. Dublin; 2001. P. 107-11.
6. Barsukov YuA, Nikolaev LV, Tamrazov RI, Tkachev SI. Sravnitel’nyi analiz khirurgicheskogo i kombinirovannogo lecheniia bol’nykh operabel’nym rakom priamoi kishki: (rezul’taty randomizirovannogo issledovaniia) [The comparative analysis of the surgical and combined treatment of patients with a resectable cancer of a rectum: (results of randomized research)]. Prakt Onkologiia. 2002;3(2):105-13.