A Study of Microenvironmental Factors Affecting the Metastasizing Potential of Ovarian Serous Carcinoma

Introduction Ovarian cancer is a leading cause of cancer mortality in women, with poor prognosis due to late detection, limited predictive biomarkers and therapeutic targets [1]. Programmed death-ligand 1 (PD-L1) expression plays a key role in immune suppression, while human epidermal growth factor receptor 2 (HER2) is linked to tumor aggressiveness [2,3]. However, the effects of these microenvironmental markers affecting the metastasizing potential of ovarian cancer remain insufficiently comprehended. Aim To investigate the immunohistochemical phenotype of ovarian tumors by analyzing the expression of PD-L1 and HER2 markers and their relationship with the biological properties of the tumor. Methods 54 cases of morphologically verified high-grade serous ovarian carcinoma (HGOSC) were selected for this study. Morphological analysis was conducted to determine pT and pN categories of TNM classification. Immunohistochemical reactions against PD-L1 (Dako 22C3 clone) and HER2 (SP3 clone) were analyzed by light microscopy. Statistical analysis was performed comparing two groups of selected cases (pN=0 vs. pN>0 of TNM) by patient’s age, pT status of TNM, status of PD-L1, HER2 expression, and neoadjuvant chemotherapy by applying descriptive statistics (mean (standard deviation), frequencies), tests of normality, Student’s T test, and χ2 test (IBM SPSS 29.0 software, statistical significance p<0.05). Results Mean age of the patients was 65.83 (9.39) years old (y.o.) with predominant pT3c (55.6%, n=30), followed by 16.7% (n=9) in pT3a, 14.8% (n=8) in pT3b, while the remaining pT2b was 9.3% (n=5) and pT2a was 3.7% (n=2). Considering pN status, pN0 (77.8%, n=42) was the predominant one among the selected HGOSC cases. Most cases were PD-L1-negative (83.3%, n=45) and HER2-negative (87%, n=47). Neoadjuvant chemotherapy was applied in 27.8% (n=15) of the selected cases. Younger patients were more likely to be confirmed with HGOSC spreading to the local lymph nodes (61.17 (9.85) y.o. vs. 67.17 (8.94) y.o; t=2.005, p=0.025). Presence of HGOSC metastasizing to the local lymph nodes was similar in different pT stages according to the TNM classification (χ2=7.473, p=0.113), status of PD-L1 (χ2=0.1, p=0.99), HER2 expression (χ2=1.234, p=0.267), and neoadjuvant chemotherapy application (χ2=0.949, p=0.33). Conclusions A detailed characterization of PD-L1 and HER2 expression in HGOSC is presented. HGOSC with metastases to the local lymph nodes is more likely to be diagnosed for younger patients. Status of HGOSC metastasizing to the local lymph nodes is similar when comparing the selected cases according to the different pT stages of TNM classification, status of PD-L1, HER2 expression, and neoadjuvant chemotherapy application, hypothesizing that microenvironmental factors affecting metastasizing potential of HGOSC may be far more complex than mechanisms of cellular growth regulation and programmed cellular death.