INTRODUCTION: Ovarian cancer is one of the leading causes of mortality in women. In 2020, 5,395 (6.2%) of diagnosed malignancies in females were ovarian in origin. It also ranked second among gynecologic malignancies after cervical cancer. The prevalence in Asian /Pacific women is 9.2 per 100,000 population. Increased mortality and poor prognosis in ovarian cancer are caused by asymptomatic growth and delayed or absent symptoms for which about 70% of women have an advanced stage (III/IV) by the time of diagnosis. The most associated gene mutations are Breast Cancer gene 1 (BRCA1) which is identified in chromosome 17q21 and Breast Cancer gene 2 (BRCA2) identified in chromosome 13. Both proteins function in the double-strand DNA break repair pathway especially in the large framework repair molecules. Olaparib is a first-line drug used in the management of ovarian cancer. It targets affected cells by inhibition of poly (ADP-ribose) polymerase (PARP) activity which induces synthetic lethality in mutated BRCA1/2 cancers by selectively targeting tumor cells that fail to repair DNA double-strand breaks (DSBs). OBJECTIVE: The study aims to determine the prevalence of pathogenic somatic mutations in BRCA1 and BRCA2 among patients diagnosed of having ovarian cancer, to characterize the identified variants into benign/ no pathogenic variant identified, variant of uncertain significance (VUS), and pathogenic, and to determine the relationship of specific mutations detected with histomorphologic findings and clinical attributes. METHODOLOGY: Ovarian cancer tissues available at the St. Luke’s Medical Center Human Cancer Biobank and formalin-fixed paraffin-embedded (FFPE) tissue blocks diagnosed as ovarian cancer from the year 2016 to 2020 were included. Determination of the prevalence of somatic BRCA1 and BRCA2 mutations using Next Generation Sequencing (NGS). RESULTS: A total of 60 samples were processed, and three samples were excluded from the analysis due to an inadequate number of cells. In the remaining 57 samples diagnosed ovarian tumors, pathogenic BRCA1/2 variants were identified in 10 (17.5%) samples. Among the BRCA1/2 positive samples, 3 (5.3%) BRCA1 and 7 (12.3%) BRCA2 somatic mutations were identified. CONCLUSION Identification of specific BRCA1/2 mutations in FFPE samples with NGS plays a big role in the management of ovarian cancer, particularly with the use of targeted therapies such as Olaparib. The use of this drug could provide a longer disease-free survival for these patients. Furthermore, we recommend that women diagnosed with ovarian cancer should be subjected to genetic testing regardless of the histologic subtypes or clinical features. Lastly, genetic testing should be done along with proper genetic counseling, especially for patients who are susceptible to these mutations.
ovarian cancer

Introduction: Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is an important component of the IGF system that regulates insulin resistance-related to tumour development. The aim of this study is to investigate the expression of IGFBP-rP1 among female cancer patients who are known or not known to have Type 2 Diabetes Mellitus (T2DM). Materials and Methods: Using a cross-sectional design, cases of ovarian and breast cancer with clinical status of T2DM were selected over a 10-year period in Hospital Universiti Sains Malaysia. Immunohistochemical staining for IGFBP-rP1 was performed on paraffin-embedded tissues and the results were correlated with the patient’s demographic and clinicopathological data. Results: A total of 152 breast cancer patients were recruited into the current study with 33.5% (51/152) patients were positive T2DM. Most of the breast cancer patients with T2DM were IGFBP-rP1-negative (66.7%, 34/51). The IGFBP-rP1 expression was significantly difference between breast cancer subjects with and without T2DM (p<0.001). There was no significant association of IGFBP-rP1 expression with data on the demographic and clinicopathological profiles of patients with breast cancer. Meanwhile, positive IGFBP-rP1 expression was evident in 44 out of 108 (40.74%) ovarian cancer cases. Among these cases, 36 were T2DM. In contrast to breast cancer cases, IGFBP-rP1 was mostly expressed among ovarian cancer patients with T2DM (66.7%, 24/36, p < 0.001). However, the -positive expression was not significantly associated with any sociodemographic and clinicopathological features of ovarian cancers. Conclusions: Majority of breast cancer patients with T2DM did not express IGFBP-rP1. In contrast, majority of the ovarian cancer patients with T2DM expressed IGFBP-rP1.
Breast cancer ; ovarian cancer

ovarian cancer ; ovarian neoplasms

Krukenberg tumors are very rare. Its origin is difficult to define especially if its gross features mimic a primary ovarian cancer. We present a case of a 24-year-old Filipino female patient with metastatic mucinous ovarian adenocarcinoma of colonic origin that mimicked primary ovarian cancer and genitourinary tuberculosis. Surgery was done and histopathology revealed that the cancer was a metastatic mucinous adenocarcinoma of colonic origin. This case highlights the importance of differentiating between benign and malignant ovarian lesions as well as distinction between primary and metastatic ovarian neoplasms. Radiological imaging has an evolving role in diagnosis of different cancers, which may be improved through better clinical correlation and developing meaningful differential diagnosis while advancing to a more strategized algorithm in the diagnostic approach.

Progress in chemotherapeutic strategy has significantly decreased side effects of the drugs used and greatly added to survival rates for ovarian cancer. On the other hand, the occurrence of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) has been reported after long-term chemotherapy. We encountered a case of therapy-related MDS that developed as a consequence of chemotherapy. A 59-year-old woman (gravida 2, para 2) stage IIIc ovarian cancer received three courses of paclitaxel and carboplatin therapy (TC) prior to primary surgery, and 16 courses of weekly TC as adjuvant chemotherapy. She exhibited pacritaxel-associated hypersensitivity reactions in the last course, so that chemotherapy was discontinued. Following three mouths of remission, a sudden rise in her tumor markers and an increase in the size of her pelvic lymphonode were discovered on PET-CT. She recieved multiple courses of chemotherary of docetaxel/carboplatin, weekly docetaxel, docetaxel/briplatin and Gemcitabin/Irinotecan between four months. In 30 months after diagnosis, complete blood count showed hemoglobin 7.7 g/dl; white cell count 4,310/μl; and platelet 7.9×104/μl. A bone marrow examination revealed MDS. She then decided against further chemotherapy, opting instead for palliative care. Fortunately, up to the present, she has not developed AML.
Therapeutic procedure ; Chemotherapy-Oncologic Procedure ; Carboplatin ; Ovarian Cancer ; L

We report a case of adenocarcinoma detected in the right pleural effusion of a 75-year-old woman. Investigations failed to reveal the site of the primary lesion, and the case was treated as primary unknown cancer. The pleural effusion disappeared after chemotherapy; however, as there was serious bone marrow suppression, the clinical course was observed at an outpatient clinic without chemotherapy. A search for the primary lesion was repeated, but it was not found. One year after first admission, a chest X-ray showed left pleural effusion. Adenocarcinoma was detected in the effusion and a tumor mass obtained from the pleural cavity. Ovarian cancer was diagnosed based on the histological, serological and MRI findings. Thus, this was a rare case of ovarian cancer in which the diagnosis was confirmed by repeated evaluation and in which the initial diagnosis had been primary unknown cancer with malignant pleural effusion only.
Ovarian Cancer ; Pleural Effusion, Malignant ; Pleural Effusion ; Unknown ; Beginning

Reported is a case of a 43 year-old Gravida 3 Para 3 (3003) admitted due to progressive abdominal enlargement, weight loss and dyspnea. Admitting Impression was Ovarian New Growth, bilateral, malignant, with secondary Pleural Effusion. She underwent Total Abdominal Hysterectomy, with Bilateral Salpingooophorectomy, bilateral lymph node dissection, peritoneal fluid cytology, and infracolic omentectomy. Histopathology report showed a Malignant Mixed Mullerian Tumor of both ovaries with metastasis to the colorectal serosa. It is noteworthy that the patient has two siblings who succumbed to advanced stage ovarian cancer. This case report will discuss the possible hereditary genetic mutations involved in the development of familialovarian carcinoma.

Gliomatosis peritonei is the deposition of benign glial implants, more commonly associated with an immature ovarian teratoma. This paper reports a case of a 24 year old gravida 1 para 1 (1001) who underwent unilateral salpingo-oophorectomy and complete surgical staging for a preoperative diagnosis of ovarian new growth, probably malignant. Intraoperatively, aside from the ovarian mass on the right, there was also note of an omental mass. Histopathology revealed a mature ovarian teratoma for the ovary and gliomatosis peritonei for the omental mass. Gliomatosis peritonei is a rare entity. There are currently no guidelines on how patients with this condition can be followed up. Transvaginal sonography and annual measurement of alpha-fetoprotein may play a role in the follow-up of patients in low resource settings.

Hereditary breast and ovarian cancer syndrome accounts for approximately 5% to 10% of breast or ovarian cancers, with which the high-penetrant BRCA1/2 genes have been associated. With the recent development of next-generation sequencing (NGS), germline mutation testing and its related medical and surgical management have been rapidly changing. In this review, we summarize the current status and perspectives of NGS testing for not only BRCA1/2 but also the other breast and ovarian cancer susceptibility genes.
Breast ; Breast Neoplasms ; Genetic Testing* ; Germ-Line Mutation ; Hereditary Breast and Ovarian Cancer Syndrome* ; High-Throughput Nucleotide Sequencing ; Ovarian Neoplasms

Objective: To investigate the mechanism of signal transducer and activator of transcription 3 (STAT3) and cancer associated fibroblasts (CAF) jointly generate chemo-resistance in epithelial-ovarian cancer and their effect on prognosis. Methods: A total of 119 patients with high-grade ovarian serous cancer who received surgery in Cancer Hospital of Chinese Academy of Medical Sciences from September 2009 to October 2017 were collected. The clinico-pathological data and follow-up data were complete. Multivariate Cox regression model was used to analyze the prognostic factors. Ovarian cancer tissue chips of patients in our hospital were prepared. EnVision two-step method immunohistochemistry was used to detect the protein expression levels of STAT3, the specific markers of CAF activation, fibroblast activating protein (FAP), and type Ⅰ collagen (COL1A1) secreted by CAF. The relationship between the expression of STAT3, FAP, COL1A1 protein and drug resistance and prognosis of ovarian cancer patients was analyzed, and the correlation between the expression of three proteins was analyzed. These results were verified through the gene expression and prognostic information of human ovarian cancer tissues collected in the GSE26712 dataset of gene expression omnibus (GEO) database. Results: (1) Multivariate Cox regression model analysis showed that chemotherapy resistance was an independent risk factor for overall survival (OS) of ovarian cancer (P<0.001). (2) The expression levels of STAT3, FAP, and COL1A1 proteins in chemotherapy resistant patients were significantly higher than those in chemotherapy sensitive patients (all P<0.05). Patients with high expression of STAT3, FAP, and COL1A1 had significantly shorter OS than those with low expression (all P<0.05). According to the human ovarian cancer GSE26712 dataset of GEO database, patients with high expression of STAT3, FAP, and COL1A1 also showed shorter OS than patients with low expression (all P<0.05), the verification results were consistent with the detection results of ovarian cancer patients in our hospital. (3) Correlation analysis showed that the protein level of STAT3 was positively correlated with FAP and COL1A1 in our hospital's ovarian cancer tissue chips (r=0.47, P<0.001; r=0.30, P=0.006), the analysis of GEO database GSE26712 dataset showed that the expression of STAT3 gene and FAP, COL1A1 gene were also significantly positively correlated (r=0.31, P<0.001; r=0.52, P<0.001). Conclusion: STAT3 and CAF could promote chemotherapy resistance of ovarian cancer and lead to poor prognosis.
Female ; Humans ; Cancer-Associated Fibroblasts/pathology* ; Carcinoma, Ovarian Epithelial ; Ovarian Neoplasms/pathology* ; Prognosis ; STAT3 Transcription Factor/metabolism* ; Drug Resistance, Neoplasm