BACKGROUND: Primary peritoneal carcinoma (PPC) at presentation often masquerades as epithelial ovarian carcinoma (OC) but behaves different with respect to treatment response, recurrence patterns and has inferior outcomes. The objective of this study is to compare the clinicopathological features and survival outcomes of PPC and OC. METHODS: Prospectively maintained database of patients presenting to the gynecologic oncology department at a tertiary hospital was reviewed between 1st January 2010 and 31st December 2020. A comparative analysis of high-grade serous stage III/IV PPC and OC was done. Demographics, treatment details, complications and survival outcomes were collected from electronic medical records. RESULTS: 151 OC and 69 PPC patients were included. A higher proportion of women with PPC had reduced performance status prior to hysterectomy with salpingo-oophorectomy, a shorter symptom to treatment interval, and large volume ascites. A significantly lower number of women with PPC (4.3 vs. 46.1%; P < 0.001) underwent primary cytoreduction, had a lower median surgical complexity score (3 vs. 4; P < 0.001) but higher recurrence rates (66.7 vs. 47.0%; P = 0.041) as compared to the patients with OC. The median progression-free survival (PFS) was 18 (15-20) months in PPC and 23 (17-28) months in OC patients (log-rank P = 0.034), while the median overall survival (OS) was similar (44 vs. 48 months; log-rank P = 0.696). The presence of extraperitoneal disease and interval cytoreduction was associated with shorter PFS. Suboptimal cytoreduction and delay in adjuvant chemotherapy beyond 6 weeks post-surgery was associated with reduced OS. CONCLUSION: PPC is an aggressive disease with lower PFS compared to OC. Commonly presenting with large volume carcinomatosis, it is not amenable for primary cytoreduction, making the usage of neoadjuvant chemotherapy a common practice and pragmatic approach.

• Klíčová slova
• clinicopathological characteristics, ovarian cancer, ovarian carcinoma, primary peritoneal carcinoma, survival outcomes,
• MeSH
• adjuvantní chemoterapie MeSH
• cytoredukční chirurgie metody   MeSH
• epiteliální ovariální karcinom patologie   MeSH
• lidé MeSH
• nádory vaječníků * farmakoterapie   chirurgie   MeSH
• neoadjuvantní terapie MeSH
• retrospektivní studie MeSH
• staging nádorů MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian carcinoma characterized by unique biological features and highly malignant characteristics including low chemosensitivity. Therefore, new therapeutic targets are needed. These could include the downstream pathways of receptor tyrosine kinases, especially the human epidermal growth factor receptor 2 (HER2). Our main objective was to characterize the HER2 status using immunohistochemistry (IHC) and FISH on 118 OCCCs, also considering the novel paradigm of HER2-zero and HER2-low status. Other aims included determination of the association between HER2 status and survival, HER2 gene DNA and RNA NGS analysis, HER2 gene expression analysis, and correlation between IHC and gene expression in HER2-zero and HER2-low cases. Cases with HER2 overexpression/amplification accounted for 5.1% (6/118), with additional 3% harbouring HER2 gene mutation. The remaining 112 (94.9%) cases were HER2-negative. Of these, 75% were classified as HER2-zero and 25% as HER2-low. This percentage of HER2 aberrations is significant concerning their possible therapeutic influence. Cases from the HER2-zero group showed significantly better survival. Although this relationship lost statistical significance in multivariate analysis, the results have potential therapeutic significance. HER2 gene expression analysis showed a significant correlation with HER2 IHC status in the entire cohort (HER2-positive vs. HER2-negative), while in the cohort of only HER2-negative cases, the results did not reach statistical significance, suggesting that gene expression analysis would not be suitable to confirm the subdivision into HER2-low and HER2-zero. Our results also emphasize the need for standardized HER2 testing in OCCC to determine the best predictor of clinical response.

• Klíčová slova
• Gynecopathology, HER2, Immunohistochemistry, Ovarian cancer, Ovarian clear cell carcinoma,
• MeSH
• amplifikace genu MeSH
• epiteliální ovariální karcinom genetika   MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie MeSH
• lidé MeSH
• nádory prsu * genetika   MeSH
• nádory vaječníků * patologie   MeSH
• receptor erbB-2 metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• receptor erbB-2 MeSH

Dedifferentiated and undifferentiated ovarian carcinomas (DDOC/UDOC) are rare neoplasms defined by the presence of an undifferentiated carcinoma. In this study, we detailed the clinical, pathological, immunohistochemical, and molecular features of a series of DDOC/UDOC. We collected a multi-institutional cohort of 23 DDOC/UDOC and performed immunohistochemistry for core switch/sucrose nonfermentable (SWI/SNF) complex proteins (ARID1A, ARID1B, SMARCA4, and SMARCB1), mismatch repair (MMR) proteins, and p53. Array-based genome-wide DNA methylation and copy number variation analyses were performed on a subset of cases with comparison made to a previously reported cohort of undifferentiated endometrial carcinoma (UDEC), small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), and tubo-ovarian high-grade serous carcinoma (HGSC). The age of all 23 patients with DDOC/UDOC ranged between 22 and 71 years (with an average age of 50 years), and a majority of them presented with extraovarian disease (16/23). Clinical follow-up was available for 19 patients. Except for 2 patients, the remaining 17 patients died from disease, with rapid disease progression resulting in mortality within a year in stage II-IV settings (median disease-specific survival of 3 months). Eighteen of 22 cases with interpretable immunohistochemistry results showed loss of expression of core SWI/SNF protein(s) that are expected to result in SWI/SNF complex inactivation as 10 exhibited coloss of ARID1A and ARID1B, 7 loss of SMARCA4, and 1 loss of SMARCB1. Six of 23 cases were MMR-deficient. Two of 20 cases exhibited mutation-type p53 immunoreactivity. Methylation profiles showed coclustering of DDOC/UDOC with UDEC, which collectively were distinct from SCCOHT and HGSC. However, DDOC/UDOC showed an intermediate degree of copy number variation, which was slightly greater, compared with SCCOHT but much less compared with HGSC. Overall, DDOC/UDOC, like its endometrial counterpart, is highly aggressive and is characterized by frequent inactivation of core SWI/SNF complex proteins and MMR deficiency. Its molecular profile overlaps with UDEC while being distinct from SCCOHT and HGSC.

• Klíčová slova
• ARID1B, SMARCA4, SMARCB1, SWI/SNF, methylation, undifferentiated ovarian carcinoma,
• MeSH
• dědičné nádorové syndromy * MeSH
• DNA-helikasy genetika   metabolismus   MeSH
• dospělí MeSH
• epiteliální ovariální karcinom MeSH
• jaderné proteiny genetika   MeSH
• karcinom * patologie   MeSH
• kolorektální nádory * MeSH
• lidé středního věku MeSH
• lidé MeSH
• malobuněčný karcinom * MeSH
• mladý dospělý MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory endometria * patologie   MeSH
• nádory mozku * MeSH
• nádory vaječníků * genetika   patologie   MeSH
• senioři MeSH
• transkripční faktory genetika   metabolismus   MeSH
• variabilita počtu kopií segmentů DNA MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA-helikasy MeSH
• jaderné proteiny MeSH
• nádorové biomarkery MeSH
• nádorový supresorový protein p53 MeSH
• SMARCA4 protein, human MeSH Prohlížeč
• transkripční faktory MeSH

Solid mural nodule within a mucinous cystic ovarian tumor occurs more often than generally presumed. One especially interesting case involving coincidental cervical carcinoma is presented. A 38-year-old woman underwent exploratory laparotomy for a right ovarian tumor. After ovarian malignancy had been diagnosed from frozen section, the bilateral salpingo-oophorectomy and hysterectomy was performed. The tumor had a unilocular cystic cavity and a mural nodule. The nodule showed undifferentiated carcinomatous features. The immunohistochemical examination revealed atypical cells in the nodule which were positive for cytokeratin, CEA, and vimentine, establishing its anaplastic nature. A synchronous cervical invasive squamous carcinoma was documented. The patient was treated with chemotherapy and radiotherapy. Currently, at 15 postoperative months, she is well and free of disease. The occurrence of ovarian mucinous cystadenocarcinoma with mural nodule of anaplastic carcinoma and cervical squamous cell carcinoma is evidently very uncommon, because we have not found a similar case in the literature.

• MeSH
• dospělí MeSH
• karcinom patologie   MeSH
• lidé MeSH
• mnohočetné primární nádory patologie   MeSH
• mucinózní cystadenokarcinom patologie   MeSH
• nádory děložního čípku patologie   MeSH
• nádory vaječníků patologie   MeSH
• spinocelulární karcinom patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

• Klíčová slova
• CARCINOMA *, CERVIX NEOPLASMS/case reports *, OVARY/neoplasms *, POLYPI *,
• MeSH
• chorobopisy * MeSH
• karcinom * MeSH
• lidé MeSH
• nádory děložního čípku * MeSH
• nádory vaječníků * MeSH
• polypy * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Epithelial ovarian carcinoma (EOC) is a highly chemosensitive tumor, but most patients with advanced EOC initially responding to first-line chemotherapy will eventually relapse. Chemosensitivity testing may offer an opportunity for the optimal selection of chemotherapeutic agents for individual patients. In the present retrospective analysis we have examined the changes in chemosensitivity profiles during the course of the disease. Chemosensitivity was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Two or more samples at least 14 days apart were obtained from 34 patients with ovarian cancer. Chemoresistance increased significantly at the second measurement only for paclitaxel and carboplatin, the most frequently used cytotoxic drugs. No significant difference compared to baseline was observed at subsequent measurements for any other cytotoxic agent studied, although a non-significant trend for increased chemoresistance was observed. In conclusion, in the present cohort only paclitaxel and carboplatin chemosensitivity changed significantly, although to a limited extent, during the course of the disease. In contrast to a limited increase of paclitaxel and carboplatin chemoresistance, no significant changes were observed for other cytotoxic agents examined. The present data indicate that chemoresistance increases, to a modest extent, against the drug most frequently used, but remains relatively stable during the course of disease, especially for agents that are not used in the therapeutic regimen.

• MeSH
• chemorezistence MeSH
• dospělí MeSH
• epiteliální ovariální karcinom MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory glandulární a epitelové * farmakoterapie   MeSH
• nádory vaječníků * farmakoterapie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Epithelial ovarian cancer (EOC) is among the top five causes of cancer-related death in women, largely reflecting early, prediagnosis dissemination of malignant cells to the peritoneum. Despite improvements in medical therapies, particularly with the implementation of novel drugs targeting homologous recombination deficiency, the survival rates of patients with EOC remain low. Unlike other neoplasms, EOC remains relatively insensitive to immune checkpoint inhibitors, which is correlated with a tumor microenvironment (TME) characterized by poor infiltration by immune cells and active immunosuppression dominated by immune components with tumor-promoting properties, especially tumor-associated macrophages (TAMs). In recent years, TAMs have attracted interest as potential therapeutic targets by seeking to reverse the immunosuppression in the TME and enhance the clinical efficacy of immunotherapy. Here, we review the key biological features of TAMs that affect tumor progression and their relevance as potential targets for treating EOC. We especially focus on the therapies that might modulate the recruitment, polarization, survival, and functional properties of TAMs in the TME of EOC that can be harnessed to develop superior combinatorial regimens with immunotherapy for the clinical care of patients with EOC.

• Klíčová slova
• Immunomodulation, Immunotherapy, Macrophages, Tumor Biomarkers, Tumor Microenvironment,
• MeSH
• epiteliální ovariální karcinom terapie   patologie   MeSH
• imunoterapie MeSH
• karcinom * patologie   MeSH
• lidé MeSH
• makrofágy spojené s nádory patologie   MeSH
• makrofágy MeSH
• nádorové mikroprostředí MeSH
• nádory vaječníků * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Epithelial ovarian carcinoma (EOC) is a relatively rare malignancy but is the fifth-leading cause of cancer-related death in women, largely reflecting early, prediagnosis dissemination of malignant disease to the peritoneum. At odds with other neoplasms, EOC is virtually insensitive to immune checkpoint inhibitors, correlating with a tumor microenvironment that exhibits poor infiltration by immune cells and active immunosuppression. Here, we comparatively summarize the humoral and cellular features of primary and metastatic EOC, comparatively analyze their impact on disease outcome, and propose measures to alter them in support of treatment sensitivity and superior patient survival.

• Klíčová slova
• female, genital neoplasms, immunologic surveillance, immunotherapy, tumor biomarkers, tumor microenvironment,
• MeSH
• epiteliální ovariální karcinom imunologie   MeSH
• imunosupresivní léčba metody   MeSH
• imunoterapie metody   MeSH
• lidé MeSH
• nádorové mikroprostředí MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVE: The aim of this study is to evaluate serum copper (Cu) and zinc (Zn) levels in patients with epithelial ovarian cancer and endometrioma. MATERIALS AND METHODS: We included 21 epithelial ovarian cancer patients, 47 endometrioma patients, 31 healthy women of reproductive age, and 10 healthy women in menopause. Cu and Zn levels and Cu/Zn ratios were compared. RESULTS: In the endometrioma group, Cu levels (P = 0.04) and Cu/Zn ratio (P < 0.01) were higher, while Zn levels (P < 0.01) were lower compared to the control group. The threshold value of 1.15 with 62% sensitivity and 61% specificity was calculated for the Cu/Zn ratio using the ROC curve (AUC = 0.688; P = 0.005). In the ovarian cancer group, Cu levels (P ≤ 0.01) and Cu/Zn ratio (P = 0.02) were higher, whereas Zn levels (P ≤ 0.02) were lower compared to the control group. The Cu/Zn ratio threshold value of 1.37 was calculated with 76% sensitivity and 90% specificity (AUC = 0.829; P = 0.004). The Zn level was lower (P = 0.02), and the Cu/Zn ratio was higher (P = 0.01) in the ovarian cancer group compared to the endometrioma group. CONCLUSION: The threshold value of the Cu/Zn ratio for ovarian cancer could be determined with a specificity of 90%, whereas the sensitivity and specificity of the Cu/Zn ratio for endometrioma were low.

• Klíčová slova
• copper, Zinc, copper zinc ratio, endometrioma, ovarian cancer,
• MeSH
• dítě MeSH
• endometrióza * diagnóza   MeSH
• epiteliální ovariální karcinom MeSH
• lidé MeSH
• měď MeSH
• nádory vaječníků * diagnóza   MeSH
• zinek MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• měď MeSH
• zinek MeSH

At odds with other solid tumors, epithelial ovarian cancer (EOC) is poorly sensitive to immune checkpoint inhibitors (ICIs), largely reflecting active immunosuppression despite CD8+ T cell infiltration at baseline. Accumulating evidence indicates that both conventional chemotherapeutics and targeted anticancer agents commonly used in the clinical management of EOC not only mediate a cytostatic and cytotoxic activity against malignant cells, but also drive therapeutically relevant immunostimulatory or immunosuppressive effects. Here, we discuss such an immunomodulatory activity, with a specific focus on molecular and cellular pathways that can be harnessed to develop superior combinatorial regimens for clinical EOC care.

• Klíčová slova
• PARP inhibitors, antiangiogenic agents, bevacizumab, immunogenic cell death, platinum derivatives, taxanes,
• MeSH
• epiteliální ovariální karcinom farmakoterapie   MeSH
• imunomodulace MeSH
• lidé MeSH
• nádory vaječníků * farmakoterapie   MeSH
• protinádorové látky * farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• protinádorové látky * MeSH