Peritoneal dissemination of high-grade serous ovarian cancer: pivotal roles of chromosomal instability and epigenetic dynamics

Konishi, Ikuo; Abiko, Kaoru; Hayashi, Takuma; Yamanoi, Koji; Murakami, Ryusuke; Yamaguchi, Ken; Hamanishi, Junzo; Baba, Tsukasa; Matsumura, Noriomi; Mandai, Masaki

doi:10.3802/jgo.2022.33.e83

Cited by 8 publications

(6 citation statements)

References 92 publications

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“…Therefore, we aimed to classify the JGOG-TR2 tumors based on molecular features rather than morphological findings. Since chromosomal instability is one of the most characteristic molecular features of HGSC (#58), we focused on CNV signature-based analysis (#59).…”

Section: Resultsmentioning

confidence: 99%

Identification of ovarian high-grade endometrioid-type tumors through multi-omics analysis: JGOG3025-TR2 study

Takamatsu,

Hillman,

Yoshihara

et al. 2024

Preprint

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Objective: There is considerable interobserver variability in the differential diagnosis between ovarian high-grade endometrioid carcinoma (HGEC) and ovarian high-grade serous carcinoma (HGSC) due to their histopathological similarities. While the association between homologous recombination deficiency (HRD) and platinum sensitivity and PARP inhibitors is well established in HGSC, the molecular characteristics of HGEC remain unclear. Methods: Fresh-frozen tissue samples from 15 ovarian HGECs and 274 ovarian HGSCs morphologically diagnosed by central pathology review in the Japanese Gynecological Oncology Group (JGOG) were subjected to targeted DNA sequencing, RNA sequencing, DNA methylation array, and SNP array analysis. Tumors were classified by unsupervised clustering based on copy number variation signatures. External datasets including 555 ovarian HGSCs and 287 endometrial high-grade carcinomas from The Cancer Genome Atlas project (TCGA-OV and TCGA-UCEC) were also analyzed. Results: Four distinct groups were identified in the JGOG cohort. C1 (n=41) showed CCNE1 amplification and poor survival. C2 (n=160) and C3 (n=59) showed a high frequency of BRCA alterations with moderate and low aneuploidy, respectively. C4 (n=22) was characterized by favorable survival, higher frequency of HGEC, absence of both BRCA alteration and CCNE1 amplification, and low levels of HRD score, ploidy, intra-tumoral heterogeneity, cell proliferation rate, and WT1 gene expression. Additionally, C4 exhibited a normal endometrium-like DNA methylation profile and was defined as an 'HGEC-type' tumor. The HGEC-type tumors were also identified in TCGA-OV and TCGA-UCEC. Conclusions: Ovarian HGEC-type tumors exhibit non-HRD status, a favorable prognosis, and endometrial differentiation, and may comprise a subset of tumors diagnosed as HGSC.

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Section: Resultsmentioning

confidence: 99%

Identification of ovarian high-grade endometrioid-type tumors through multi-omics analysis: JGOG3025-TR2 study

Takamatsu,

Hillman,

Yoshihara

et al. 2024

Preprint

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“…Overall, these studies demonstrated that early tumors of serous intratubal carcinoma in the fallopian tube already have important DNA changes necessary for OC development. These findings suggest that serous fallopian tube carcinoma migrated to the ovary and carcinoma progressed in the ovary [ 47 , 48 , 50 ] ( Fig. 1 ).…”

Section: Fallopian Tube Epithelium As the Origin Of Serous Ovarian Ca...mentioning

confidence: 99%

“…Some researchers have attributed the most common type of OC to the fallopian tube, a thin fibrous tube connecting the ovary to the uterus. Previous findings obtained from nine OC patients indicated that the genomic origin of many ovarian tumors was the fallopian tube [ 47 , 48 ]. Previous studies provided insights into the origin of OC and the potential of novel interventions for the prevention and treatment of OC.…”

Section: Fallopian Tube Epithelium As the Origin Of Serous Ovarian Ca...mentioning

confidence: 99%

“…Ovarian SC is an intra-ovarian metastasis of a primary malignant tumor, an STIC that does not clearly form a dominant tubal mass like other solid cancers. When STIC reaches the ovaries, progression to metastatic disease is estimated to rapidly occur within an average of 2 years [ 48 , 51 ].…”

Section: Difficulty Of Preoperative Diagnosis At An Early Stage For Hgscmentioning

confidence: 99%

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Molecular Histopathology for Establishing Diagnostic Method and Clinical Therapy for Ovarian Carcinoma

Hayashi¹,

Konishi²

2023

J Clin Med Res

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Ovarian carcinoma (OC) is considered the deadliest gynecological malignancy. It is typically diagnosed in the advanced stages of the disease, with metastatic sites widely disseminated within the abdominal cavity. OC treatment is challenging due to the high rate of disease recurrence, which is further complicated by acquired chemoresistance caused by the reversion of the pathological variant. Therefore, more effective treatments are still being sought. Histologically, OC is classified into serous, mucinous, endometrioid, clear cell, and transitional cell carcinomas and malignant Brenner tumor. Recent clinicopathological and molecular biological studies demonstrated that these subtypes differ in histogenesis and anti-tumor agent sensitivity. In Japan, the incidence rates of the histological types of OC, namely, serous carcinoma, mucinous carcinoma, endometrioid carcinoma, and clear cell adenocarcinoma, are 39%, 12%, 16%, and 23%, respectively. Serous carcinoma is classified as high or low grade, with the former accounting for the overwhelming majority. In this study, the molecular pathological classification of OC has been described based on the characteristics of the two types of OC, types 1 and 2. Compared with Europe and the United States, Japan has a higher prevalence of type 1 OC and a lower prevalence of type 2 OC. The prevalence of each type of OC varies by race. It has been elucidated that the prevalence rate of each type of ovarian cancer in Asian countries is similar to that in Japan. Thus, OC is a heterogeneous disease. Furthermore, OC has been attributed to molecular biological mechanisms that vary among tissue subtypes. Therefore, it is necessary to conduct treatment based on accurate diagnoses of each tissue type and establish an optimal treatment strategy, and now is the transition period.

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“…STIC could be a likely precursor lesion of high-grade serous pelvic carcinomas, carcinosarcoma, and undifferentiated carcinoma with an incidence of 0.6–7% in breast cancer 1/2 gene carriers or women with a strong family history of breast or ovarian carcinoma. Therefore, epithelial malignant cells and STICs that occur in the epithelial cell tissue of the fallopian tubes and in the fimbriated end are the primary tumors that metastasize into the ovary and form micrometastases [ 16 , 17 , 18 ]. In forming a micrometastatic niche in multiple organs, epithelial and stromal cells in contact with circulation tumor cells (CTCs) are initialized by secretory factors from CTCs that compose the micrometastatic niche [ 8 , 9 , 10 , 11 ].…”

Section: Case Reportmentioning

confidence: 99%

Pathological Evidence for Residual SARS-CoV-2 in the Micrometastatic Niche of a Patient with Ovarian Cancer

Hayashi

Sakai

Yaegashi

et al. 2022

CIMB

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In previous clinical studies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in cancer patients has a high risk of aggravation and mortality than in healthy infected individuals. Inoculation with coronavirus disease 2019 (COVID-19) vaccine reduces the risk of SARS-CoV-2 infection and COVID-19 severity. However, vaccination-induced anti-SARS-CoV-2 antibody production is said to be lower in cancer patients than in healthy individuals. In addition, the rationale for why the condition of patients with cancer worsens with COVID-19 is not well understood. Therefore, we examined the infection status of SARS-CoV-2 in the primary tumor and micrometastasis tissues of the patient with cancer and COVID-19. In this study, the expression of angiotensin-converting enzyme 2 (ACE2) was observed, and SARS-CoV-2 particles was detected in ovarian tissue cells in contact with the micrometastatic niche of the patient with high-grade serous ovarian cancer. We believe that the severity of COVID-19 in patients with cancer can be attributed to these pathological features. Therefore, the pathological findings of patients with advanced and recurrent ovarian cancer infected with SARS-CoV-2 may help decrease COVID-19 severity in patients with other cancer types.

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Peritoneal dissemination of high-grade serous ovarian cancer: pivotal roles of chromosomal instability and epigenetic dynamics

Cited by 8 publications

References 92 publications

Identification of ovarian high-grade endometrioid-type tumors through multi-omics analysis: JGOG3025-TR2 study

Identification of ovarian high-grade endometrioid-type tumors through multi-omics analysis: JGOG3025-TR2 study

Molecular Histopathology for Establishing Diagnostic Method and Clinical Therapy for Ovarian Carcinoma

Pathological Evidence for Residual SARS-CoV-2 in the Micrometastatic Niche of a Patient with Ovarian Cancer

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