scholarly journals 2 - Identification of neoantigens from non-primary tumor tissue in patients with recurrent ovarian cancer by sequencing and subsequent HLA ligand mass spectrometry

Author(s):  
Roisin O'Cearbhaill ◽  
Oliver Zivanovic
2019 ◽  
Vol 65 (3) ◽  
pp. 422-426
Author(s):  
Dinara Dolgova ◽  
Snezhanna Gening ◽  
Tatyana Abakumova ◽  
Inna Antoneeva ◽  
Tatyana Gening ◽  
...  

Chemoresistance is one of the main causes of treatment failure in advanced ovarian cancer (OC). In order to identify predictors of chemoresistance, 30 patients with ascitic form of OC, who received neoadjuvant chemotherapy (NACT) according to AP regimen, were examined. In the epithelial cells of ascites and in tumor tissue after NACT, expression of the VEGFa, ABCB1 and ERCC1 genes was assessed by PCR-RT. The effectiveness of NACT was assessed using the criteria of therapeutic pathomorphosis, survival - using the Kaplan-Meier criterion, the relationship of clinical and molecular parameters - using the Mann-Whitney criterion. Results. We established that in 43% of patients the response to NACT was absent (CRS1), the significant response (CRS2) was in 35% of cases, and the complete response (CRS3) was in 21% of cases. VEGFa expression was increased in ascites in 17% of cases, in tumor tissue - in 33% in the CRS1 group. In groups with CRS 2,3, overexpression of VEGFa in ascites was detected in 25% of cases, in tumor tissue in 37.5%. ABCB1 mRNA expression was increased after NACT in 50% of cases in the CRS1 group and in 25% of cases in the CRS 2,3 group. Thus, platinum-based NACT initiates an increase in the expression of VEGFa and ABCB1 in tumor tissue. We established that in case of high expression (ERCC + / VEGF + / ABCB1 +) in ascites, there is a statistically significant increase in relapse-free survival compared with the group with low or absent expression (p = 0.012). The overall survival rate was 41.8 months in patients with overexpression of the studied genes in the tissue of the primary tumor after NACT and 25.3 months in patients with low expression (p = 0.058). Conclusion. The levels of ERCC1, VEGFa and ABCB1 mRNA in ascitic cells before NACT and in the primary tumor after NACT according to the AP scheme can serve as a predictor of the effectiveness of this treatment in ascitic OC.


Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 924 ◽  
Author(s):  
Sabine Heublein ◽  
Heiko Schulz ◽  
Frederik Marmé ◽  
Martin Angele ◽  
Bastian Czogalla ◽  
...  

Ovarian cancer (OC) spread to retro-peritoneal lymph nodes is detected in about one out of two patients at primary diagnosis. Whether the histologic pattern of lymph node involvement i.e., intra-(ICG) or extracapsular (ECG) cancer growth may affect patients’ prognosis remains unknown. The aim of the current study was to analyze the prevalence of ECG and ICG in lymph node positive ovarian cancer. We further investigated whether ECG may be related to patients’ prognosis and whether biomarkers expressed in the primary tumor may predict the pattern of lymph node involvement. Lymph node samples stemming from 143 OC patients were examined for presence of ECG. Capsular extravasation was tested for statistical association with clinico-pathological variables. We further tested 27 biomarkers that had been determined in primary tumor tissue for their potential to predict ECG in metastatic lymph nodes. ECG was detected in 35 (24.5%) of 143 lymph node positive patients. High grade (p = 0.043), histologic subtype (p = 0.006) and high lymph node ratio (LNR) (p < 0.001) were positively correlated with presence of ECG. Both ECG (p = 0.024) and high LNR (p = 0.008) were predictive for shortened overall survival. A four-protein signature determined from the primary tumor tissue was associated with presence of concomitant extracapsular spread in lymph nodes of the respective patient. This work found extracapsular spread of lymph node metastasis to be a common feature of lymph node positive ovarian cancer. Since ECG was positively associated with grade, LNR and shortened overall survival, we hypothesize that the presence of ECG may be interpreted as an indicator of tumor aggressiveness.


2021 ◽  
Vol 30 (4) ◽  
pp. 35-42
Author(s):  
Alexei Alexandrovich Votintsev ◽  

The method of computer morphometry of stroma components and evaluation of stromal-parenchymal relationships in the primary tumor node of serous ovarian cancer was used. A high potential for malignancy of tumor tissue, characterized by the resumption of tumor growth after radical treatment, is observed with the predominance of the epithelial component over the stroma, with a small number of necrosis in the tumor node, low density of microcirculatory vessels in the tumor, and the predominance of fi broblastic elements in the cellular microenvironment of the tumorassociated stroma.


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