Yakimenko A. Pathomorphological and immunohistochemical criteria of prognosis in colorectal cancer

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

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  • 222 - Медицина


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ДФ 64.609.047

The Kharkiv Medical Academy of Postgraduate Education


Colorectal cancer (CRC) is one of the most common malignancy in the world. The recurrence rate of CRC is 30-40%, which in 40-50% occurs in the first few years after surgical removal of the tumor. CRC is also a tumor with a high mortality rate of patients, which is the 3rd most common malignancy of all tumors. The prognosis of CRC firstly depends on the completeness of tumor resection and on stage according to the TNM system, but the recurrence and lethal outcome of patients in each stage of the disease are significantly different. Some histological and molecular biological features may play an important role in determining the clinical behavior of the tumor and the prognosis of the disease. The dissertation is devoted to improvement of morphological criteria for the prognosis of colorectal cancers based on studying clinical, morphological and molecular biological characteristics of primary tumors with different clinical behavior and prognosis. The material was presented by 321 cases of CRC of dead patients in hospitals of Kharkiv, autopsy data and histological examination of surgically removed tumors were considered. Cases of CRC stage IIA and IIIB, T3 according to the TNM system were selected. Two groups of research are formed. Group I included primary CRC without recurrence. The average recurrence-free period was 5 years (62.5 ± 16.5 months) with a minimum of 45 months and a maximum of 96 months. Group II - primary CRC with recurrence (local manifestations or metastases). Group II had two subgroups: IIA - with recurrences within 5 years from the date of tumor removal, which did not lead to death, the progression of the tumor process is weak. IIB - with the occurrence of recurrence with a fatal consequence of the generalization of tumor process within 5 years from the date of removal of the primary tumor. Also, in the study groups selected adenocarcinomas with the same ratio of tumors by differentiation: one case of CRC G1, 14 cases of G2, 5 cases of G3 in each group. The mean age of patients was 66.8 ± 7.8 years. The youngest is 48 years old, the oldest is 87 years old. 25.0% of the studied CRCs were localized in the right half of the colon, 53.3% in the left half, and 21.7% in the rectum. Tumor size did not exceed 5 cm in 60% (45/60) cases. Metastases to regional lymph nodes were detected in 45.0% (27/60) of cases. The median duration of recurrence was 19 ± 8.7 months. Immunohistochemical study was performed using 11 markers: monoclonal antibodies to cytokeratin 7, 20, E-cadgein, vimentin, N-cadherin, CD44, CD34, VEGF, smooth muscle actin alpha, CD3, CD68. It was found that among the deaths in the hospitals CRC was the cause of death in 4.83% (321/6635). The localization of the tumor was the sigmoid colon and rectosigmoid zone - in 37.5% of patients, the area of the cecum, ileocecal angle and appendix - in 16.5%, rectum - 11.9%. Stage IV was detected in only 43.6% (140/321) of cases. Among the causes of death of patients with CRC, the most common were local complications - generalization of the tumor process and perforation of the tumor - in 27.1 and 18.3% of patients, respectively. The study of prognostic criteria for recurrence and lethal outcome of primary CRC stages IIA-IIIB revealed that risk factors for recurrence include: the presence of metastases to regional lymph nodes, vascular invasion, short distance from the edge of resection, no adjuvant chemotherapy. Recurrence with fatal progression of the tumor in the first 5 years after tumor removal is associated with: localization of regional lymph nodes, lack of adjuvant chemotherapy after tumor removal, early recurrence. The obtained data allowed to form prognostic criteria for recurrence and lethal outcome of patients with stage IIA-IIIB CRC, as well as to determine clinical-morphological and molecular-biological criteria for favorable prognosis and those with limited prognostic value. It was purposed the optimal panel of ICH markers with assessment of parenchymal and stromal components of tumors for determining the biological behavior and prognosis of the disease. Also, a mathematical model was approved using the linear regression method, which allows for 81.4% and 63.1% of predicting the development of recurrance and recurrance with a lethal complication.


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