Shtabinskaya T.T., Bodnar M.

Grodno State Medical University, Belarus

PROGNOSTIC SIGNIFICANCE OF ENDOGLIN EXPRESSION IN COLON ADENOCARCINOMA WITH SYNCHRONOUS METASTASES

There is evidence that endoglin in tumor cells provides mobility, increases protease activity and raises the invasive potential [1]. In many tumors with predominantly lymphogenous metastasis, including colorectal adenocarcinoma, endogenine expression was detected in lymphatic and endothelial cells and the risk of development of lymph node metastases was determined from the number of CD105-positive vessels [2, 3].

Purpose: to assess the expression of CD105 in colon adenocarcinoma depending on the presence of metastases and its significance for predicting the course of the disease.

Materials and methods: 72 cases of colorectal adenocarcinoma were investigated. The study was performed on paraffin sections using mouse monoclonal antibodies to CD105 (Ab114052, clon 3А9) according to standard procedure. Quantitation of the level of expression was described in the previous article [4]. Statistical analysis was performed using STATISTICA 10.0 (SNAXAR207F394425FA-Q).

Results:

In 44 patients (61.1%) were detected metastases in the regional lymph nodes (pN1b - 29 cases, pN1c - 4, pN2a - 11). During the follow-up from the progression of the disease, 37 patients died (51.4%). The median of the adjusted disease-free survival was 2.5 (1.6-4.2) years. In 12 (16.7%) patients were found hematogenous metastases at the time of diagnosis, in 8 patients (11.1%) – both lymphogenous and hematogenic (in the liver and lungs - 75% and 25%, respectively). New liver, lungs, kidneys, bones and ovaries metastases appeared in the course of time in 15 patients (20.8%), while in 6 (8.33%) they were first detected after surgical removal of the tumor. The median appearance of distant metastases was 1.83 (1.23-4.06) years.

The level of CD105 vascular positivity is significantly higher in a tumor with lymphogenic and hematogenous metastases (pN0 – 0,462 (0,444-0,542) and pN1-2 – 0,769 (0,699-0,856), p <0.001; рМ0 – 0,696 (0,469-0,754) and рМ1 – 0,933 (0,856-0,976); р<0,001). CD105 expression was significantly higher in the group of patients who developed new distant metastases, but no significant differences were observed with time of their appearance (p>0.05).

The construction of a multi-factor model for predicting the 5-year outcome depending on the clinical and morphological parameters was carried out using Cox regression by a direct step-by-step method. The grouping sign was the outcome of cancer at 5 years from the moment of surgery, as assessed by the adjusted disease-free survival. Due to the fact that the distribution was different from normal (p <0.05), the Spearman rank correlation was calculated to check the variables for cross-correlation. Independent clinical and morphological variables are weakly correlated and, therefore, can be used as independent variables in regression. It has been established that only metastasis, both hematogenous and lymphogenic, significantly affects the five-year survival rate.

Values of the likelihood function and statistical model criteria for each of the regression steps are presented in Table 1.

Table 1. – Step-by-step evaluation of the regression model criteria

Omnibus Tests of Model Coefficients^c,d
Step	-2 Log Likelihood	Overall (score)			Change From Previous Step			Change From Previous Block
		Chi-square	df	Sig.	Chi-square	df	Sig.	Chi-square	df	Sig.
1^a	295,500	17,883	1	,000	12,388	1	,000	12,388	1	,000
2^b	287,471	27,858	3	,000	8,029	2	,018	20,416	3	,000

The coefficients of the model are significant and their numerical values will allow us to interpret the result obtained. The numerical values of the coefficients of independent variables and their characteristics are presented in Table 2.

Table 2. – Characteristics of coefficients of independent variables included in the forecast model of a five-year survival

Variables in the Equation
		B	SE	Wald	df	Sig.	Exp(B)
Step 2	M	-1,589	,384	17,139	1	,000	,204
	N			9,980	2	,007
	N(1)	-1,232	,443	7,728	1	,005	,292
	N(2)	-1,241	,424	8,563	1	,003	,289

As can be seen from Table 2, significant morphological risk factors are: the presence of hematogenous metastases and the degree of lymphogenous spread of the tumor. The presence of synchronous hematogenous metastases reduces the survival rate of the patient by 0.204 times, and an increase in pN by 1 reduces the survival rate of 0.292 and 0.289, respectively.

Conclusion: Hyperexpression of endoglin in colon adenocarcinoma is indicative of hematogenous and lymphogenous dissemination of the tumor, but it should not be used as an independent prognostic factor.

Literature:

1. Endoglin expression in metastatic breast cancer cells enhances their invasive phenotype / D. Oxmann [et al.] // Oncogene. – 2008. – Vol. 27. – №25. – P. 3567-3575.

2. Royston, D. Mechanisms of lymphatic metastasis in human colorectal adenocarcinoma / D. Royston, D.G. Jackson // J Pathol. – 2009. – Vol. 217. – №5. – P. 608-619.

3. Expression of endoglin (CD105) in cervical cancer / H.J. Zijlmans [et al.] // Br J Cancer. – 2009. – Vol. 100. – №10. – P. 1617-1626.

4. Штабинская, Т.Т. Прогностическое значение уровня экспрессии фактора роста эндотелия сосудов в колоректальном раке / Т.Т. Штабинская [и др.] // Научно-практический журнал УО «Гродненский государственный медицинский университет». – 2015. - № 3(51). – С. 64-69.