Hryhorenko V. Morphological criteria for diagnosis and prognosis of serous ovarian cancer

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0822U100591

Applicant for

Specialization

  • 222 - Медицина

17-01-2022

Specialized Academic Board

ДФ 64.609.042

The Kharkiv Medical Academy of Postgraduate Education

Essay

The dissertation is devoted to the improvement of diagnostic criteria for the occurrence of serous carcinomas of low malignancy (LGSC) in women with a history of serous borderline ovarian tumors (SBOT), as well as diagnostic criteria for predicting the recurrence of serous carcinomas based on a comprehensive study of clinical features of tumors, morphological and immunohistochemical features. The material numbered 200 studied tumors of various degrees of malignancy. The study groups are represented by 50 cases of SBOT, among which LGSC was diagnosed in 12 cases over the next 5 years; 43 cases of LGSC, of which 13 cases were diagnosed with relapse within the next 24 months and 107 cases of HGSS, of which 81 cases were diagnosed with relapse within the next 24 months. Immunohistochemical (IHC) study was performed using 19 markers: markers CK7 and CK20 were used to assess epithelial-mesenchymal transformation (EMT), E-cadherin - a marker of adhesion between epitheliocytes and Vimentin - an intermediate filament of mesenchymal origin cells, Ki-67 indicates proliferative activity, TGF-β - to assess the invasive capacity of the tumor, VEGF - to assess vascularization, markers ER and PR - to assess the hormonal status of the tumor, p53 - to assess proapoptotic activity and bcl-2 to assess antiapoptotic activity, markers of stem tumor cells (STCS) CD133, CD117, CD44 and Sox2, as well as markers of immunocellular infiltration CD3, CD4, CD8, CD68 and CD20. The analysis of age features of studied groups of tumors showed that for group of SBOT the average age of patients without LGSC was 42.18 ± 0.63 years, and in patients with subsequent LGSC 40.42 ± 1.18 years, with the occurrence of LGSC in women with a history of SBOT is characterized by age ≤45 years (p = 0.001). In the LGSC group for non-recurrent tumors, the mean age of patients was 42.08 ± 2.43 years, and for recurrent tumors 42.97 ± 0.81, the two subgroups did not differ in age (p = 0.95). In the HGSC group, all tumors were recorded in patients aged ≥56 years, in the group of malignant neoplasms (MN) without recurrence, the average age of patients was 63.4 ± 0.93 years, and in the group of recurrent carcinomas 63.30 ± 0.24 years, there was no tendency to increase the age in the group of recurrent HGSC (p = 0.63). An analysis of the location of ovarian tumors was performed, during which it was found that 41 (82%) tumors from the group of SBOT were located monolaterally and 9 (18%) bilaterally. In the LGSC group, the vast majority of CHD was diagnosed bilaterally (33/43 cases) and 10 tumors were found in 1 ovary. On the one hand, there were only 5/107 tumors in the HGSC group, and 102/107 tumors were bilateral. The study of tumors by localization and recurrence didn`t show statistically significant results either in the group of SBOT (p = 1), or in LGSC (p = 0.6), or in HGSC (p = 0.16). The next studied clinical factor was the diameter of tumor. In the group of SBOT without further occurrence of LGSC, the average diameter was 6.78 ± 0.5 cm, and in the group with subsequent occurrence of LGSC 10.16 ± 0.58 cm, there was a tendency to associate recurrence with tumor diameter ≥10 cm ( p <0.001). In the LGSC group, the diameter of non-recurrent tumors was 5.48 ± 0.34 cm, and for tumors with recurrences, the median diameter was 10.78 ± 0.51 cm, and there was also a tendency to recurrence in tumors ≥10 cm (p <0.001). . In all studied HGSCs, the average tumor diameter was 11.42 ± 0.24 cm and didn`t affect the possibility of recurrence (p = 0.06). All tumors were distributed according to the stage of ovarian cancer by FIGO. In the group of SBOT at the first stage 29 (58%) cases were diagnosed, and at the second 21 (42%) cases, while for SBOT with further development of LGSC stage II according to FIGO is characteristic. In the LGSC group, 6 (13.95%) tumors were diagnosed in stage I, 21 (48.84%) tumors in stage II, 14 (32.56%) tumors in stage III and 2 (4.65%) observations were attributed to stage IV of the disease by FIGO. Recurrent LGSCs were characterized by stage III-IV disease (p <0.001). In the HGSC group, stage I of the disease wasn`t recorded at all, a small number of observations of 12.15% (13/107) were recorded in stage II and the vast majority of tumors were diagnosed in stage III of the disease - 64.49% (69/107) with fewer cases. Stage IV 23.36% (25/107). Recurrent HSCs, as well as LGSCs, are also characterized by stage III-IV disease (p = 0.0006).Thus, results obtained during the study allow, on the one hand, to understand the role of important IHC markers in the process of tumor progression and recurrence, on the other - to make a comprehensive clinical and morphological and IHC panel, as well as mathematical models to diagnose the risk of LGSC in patients with a history of SBOT and prediction of recurrence of highly and poorly differentiated serous ovarian carcinoma indicating critical ranges of marker values for the IHC panel.

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