by Jason Wasserman MD PhD FRCPC
April 16, 2026
High-grade serous carcinoma of the ovary is the most common type of ovarian cancer. It develops from epithelial cells that closely resemble the cells lining the inside of the fallopian tube. High-grade serous carcinoma accounts for about 70% of all ovarian carcinomas, and many cases are diagnosed after the cancer has already spread within the abdomen. Even though it is an aggressive cancer, it often responds well to chemotherapy, particularly at the start of treatment. This article will help you understand the findings in your pathology report — what each term means and why it matters for your care.
What are the symptoms?
The symptoms of high-grade serous carcinoma are often nonspecific and may develop gradually. Common symptoms include abdominal swelling or bloating, pelvic or abdominal pain, a feeling of fullness after eating small amounts of food, changes in bowel habits, and urinary frequency or urgency. Some people also experience fatigue or unexplained weight loss.
A blood test called CA-125 is elevated in most patients with this cancer. However, CA-125 is not specific for ovarian cancer and can be elevated in many other conditions. For this reason, it is most useful for monitoring the disease over time rather than for making the diagnosis on its own.
What causes high-grade serous carcinoma of the ovary?
The exact cause is not fully understood. Most high-grade serous carcinomas are now believed to begin in the fimbria — the finger-like fringe at the end of the fallopian tube closest to the ovary. Tumor cells appear to originate there and then spread to the surface of the ovary and to other sites inside the abdomen.
Risk factors include increasing age and a family history of ovarian or breast cancer. About 15–20% of cases occur in people who carry an inherited mutation in the BRCA1 or BRCA2 genes, which normally help cells repair damaged DNA. Additional risk is conferred by other inherited mutations in DNA repair genes, including Lynch syndrome genes.
Protective factors include pregnancy, breastfeeding, and use of oral contraceptives, all of which reduce the total number of ovulation cycles over a lifetime.
How is the diagnosis made?
The diagnosis is usually made after a tissue sample is examined under the microscope by a pathologist. The sample may be obtained during surgery to remove the tumor, or by a needle biopsy of a pelvic or abdominal mass if surgery is not performed first. In some cases, a biopsy is taken from a site of spread — such as the omentum (the fatty tissue hanging from the stomach and intestines) or the peritoneum (the lining of the abdominal cavity) — to confirm the diagnosis before definitive treatment begins.
Under the microscope, high-grade serous carcinoma can grow in several patterns, including papillary (finger-like projections), solid sheets of cells, gland-like structures, and slit-like spaces. The tumor cells show marked nuclear atypia — meaning their nuclei vary greatly in size and shape and look very abnormal. Dividing cells (called mitotic figures) are numerous, and areas of dead tumor tissue (necrosis) are common. Some tumors show a specific combination of patterns described by pathologists as “SET” (solid, endometrioid-like, and transitional-like), which may be associated with defects in DNA repair.
To confirm the diagnosis and distinguish high-grade serous carcinoma from other ovarian cancer types, the pathologist uses a laboratory technique called immunohistochemistry (IHC). IHC uses antibodies to detect specific proteins inside the cells. Most high-grade serous carcinomas show diffuse nuclear staining for WT1 and PAX8, confirming their origin from Müllerian-type epithelium. Most tumors also show abnormal p53 staining — either strong staining in nearly all tumor cells, or a complete absence of staining — reflecting the near-universal mutation of the TP53 gene in this cancer type. Many tumors also stain strongly for p16, CK7, CA-125, and the estrogen receptor (ER). These IHC results help pathologists confirm the diagnosis and rule out other cancer types that can look similar.
Once the cancer is confirmed, imaging — typically CT of the chest, abdomen, and pelvis, and sometimes MRI or PET-CT — is used to determine how far the tumor has spread and to guide staging and treatment planning.
Histologic grade
High-grade serous carcinoma is not assigned a histologic grade in the traditional sense because its high grade defines it. Unlike some other cancers where pathologists distinguish low-grade from high-grade forms of the same tumor type, high-grade serous carcinoma is a specific diagnosis that by definition refers to a high-grade cancer. It is always considered an aggressive tumor. A separate tumor type — low-grade serous carcinoma — exists and behaves very differently, but it is a distinct diagnosis, not a lower grade of the same cancer.
Tumor spread
High-grade serous carcinoma commonly spreads within the abdomen. Tumor cells may involve the peritoneum (the thin lining of the abdominal cavity), the omentum, the surfaces of the bowel, the diaphragm (the dome-shaped muscle beneath the lungs), and other abdominal organs. Spread to the surface of the liver or spleen is common in advanced disease; spread inside the liver or spleen (into the organ substance itself) is less common and indicates a higher stage.
Because spread beyond the ovary is present in the majority of patients at the time of diagnosis, the pathology report often includes findings from multiple tissue samples collected during surgery.
Ovarian capsule status
The pathologist will note whether the outer covering of the ovary — called the capsule — is intact or ruptured, and whether a tumor is present on the outer surface. These findings affect the stage:
- Intact capsule, no surface tumor — Suggests the cancer may still be contained within the ovary, which is associated with an earlier stage.
- Ruptured capsule or tumor on the surface — Indicates the cancer has broken through or reached the surface of the ovary, which increases the stage even if no other spread is found.
- Intraoperative rupture — If the capsule ruptures during surgery rather than before, this is noted separately and also affects staging.
Lymphovascular invasion
Lymphovascular invasion means that tumor cells have been found inside the small blood vessels or lymphatic channels within the tissue. This finding suggests that tumor cells may have had an opportunity to travel to lymph nodes or other organs, and it can influence staging and treatment planning.
Lymph nodes
Lymph nodes are small, bean-shaped structures that help filter the body’s lymphatic fluid and support the immune system. In ovarian cancer surgery, lymph nodes from the pelvis and along the major abdominal blood vessels (para-aortic nodes) are often removed and examined. If tumor cells are found in the lymph nodes, the cancer is considered to have spread beyond the ovary, and the stage increases.
The pathology report will describe the total number of lymph nodes examined, the number containing tumor cells, the size of the largest deposit, and the location of any involved nodes. Lymph node deposits are classified by size:
- Isolated tumor cells (pN0(i+)) — Clusters measuring 0.2 mm or less; not counted as definitive nodal metastases in all staging systems.
- Small metastases (pN1a) — Deposits measuring more than 0.2 mm and up to 10 mm.
- Large metastases (pN1b) — Deposits measuring more than 10 mm.
Biomarker and molecular testing
Biomarker testing is an essential part of the workup for high-grade serous carcinoma of the ovary. The results help identify patients most likely to benefit from targeted therapies and immunotherapy, and — critically — whether a cancer is caused by an inherited gene mutation that may affect other family members. Testing is typically performed on tumor tissue and, in the case of BRCA testing, also on a blood or saliva sample.
BRCA1 and BRCA2
BRCA1 and BRCA2 are genes whose normal job is to repair serious breaks in DNA. When one of these genes is mutated, the cell loses one of its main DNA repair tools. In high-grade serous carcinoma, BRCA mutations are present in approximately 20–25% of cases — roughly half are inherited (germline), and half are acquired within the tumor (somatic).
BRCA testing is performed on both tumor tissue and a blood or saliva sample. Testing the tumor tells your doctors whether the cancer itself carries a BRCA mutation and may help guide treatment. Testing the blood or saliva determines whether the mutation was inherited — a result with implications for your blood relatives, who may face an elevated risk of ovarian, breast, and other cancers.
Tumors with BRCA mutations tend to be more sensitive to platinum-based chemotherapy. They are eligible for maintenance therapy with PARP inhibitors — drugs that exploit the DNA repair defect caused by the mutation. Approved PARP inhibitors for BRCA-mutated ovarian cancer include olaparib (Lynparza), niraparib (Zejula), and rucaparib (Rubraca), given after a response to first-line platinum chemotherapy. In clinical trials, PARP inhibitor maintenance has been shown to delay cancer progression compared to observation alone significantly.
Results are reported as pathogenic mutation detected, no mutation detected, or variant of uncertain significance (VUS). A VUS means a change was found in the gene, but its significance is not yet known; it does not change treatment decisions. If a germline (inherited) BRCA mutation is found, referral to a genetic counselor is strongly recommended for you and your family members.
For more details, see the dedicated article: BRCA1 and BRCA2 in Ovarian Cancer.
Homologous recombination deficiency (HRD)
Homologous recombination is one of the cell’s main mechanisms for repairing serious DNA damage. When this system is not working — a state called homologous recombination deficiency, or HRD — the tumor becomes more sensitive to treatments that exploit that repair failure, especially platinum chemotherapy and PARP inhibitors.
All tumors with a BRCA mutation are HRD-positive by definition. However, an additional 20–30% of high-grade serous carcinomas are HRD-positive for other reasons—for example, silencing of the BRCA1 gene through promoter methylation or mutations in other DNA repair genes. HRD testing identifies these patients who may also benefit from PARP inhibitors, even if their BRCA test is negative.
HRD testing is performed on tumor tissue and measures the accumulated pattern of DNA damage that builds up when homologous recombination has been failing over time — sometimes described as genomic scarring. Results are typically reported as HRD-positive or HRD-negative, often along with a numerical score. Whether an HRD-positive result qualifies a patient for PARP inhibitor therapy depends on the specific drug and the regulatory approval in their country.
For more details, see the dedicated article: Homologous Recombination Deficiency (HRD) in Ovarian Cancer.
Mismatch repair proteins (MMR)
Mismatch repair proteins are a team of proteins — MLH1, PMS2, MSH2, and MSH6 — that work together to fix small errors that occur when DNA is copied inside the cell. When one or more of these proteins is missing or not working, the cancer is described as mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H).
Mismatch repair deficiency is uncommon in high-grade serous carcinoma — it occurs in roughly 1–2% of cases — but when present, it has two important implications. First, it may suggest the cancer is a different tumor type than expected, such as a mixed or ambiguous carcinoma, and the pathologist may consider additional testing. Second, dMMR/MSI-H tumors may be eligible for immunotherapy with pembrolizumab (Keytruda), which has pan-tumor approval for dMMR/MSI-H solid tumors that have progressed after prior treatment.
Testing is performed by immunohistochemistry on tumor tissue. Results are reported as retained expression (normal) or loss of expression for each of the four proteins. When MLH1 and PMS2 are both lost, additional testing for a BRAF V600E mutation or MLH1 promoter methylation is often performed to distinguish sporadic (non-inherited) loss from Lynch syndrome. If a pattern consistent with Lynch syndrome is identified — particularly loss of MSH2 or MSH6, or unexplained MLH1/PMS2 loss — referral to a genetic counselor is recommended. Lynch syndrome is an inherited condition that significantly raises the lifetime risk of ovarian, endometrial, colorectal, and several other cancers.
p53
p53 is a protein that acts as a guardian of the cell, monitoring for DNA damage and activating repair processes. It is produced by a gene called TP53. In high-grade serous carcinoma, TP53 is mutated in nearly 100% of cases — a defining molecular feature of this tumor type. For this reason, p53 testing by immunohistochemistry is part of the diagnostic workup rather than a test that changes treatment decisions. An abnormal p53 result — either diffusely strong staining throughout the tumor, complete absence of staining, or cytoplasmic staining — supports the diagnosis of high-grade serous carcinoma. A normal (wild-type) p53 staining pattern in a tumor that otherwise looks like high-grade serous carcinoma would raise the possibility of an alternative diagnosis.
PD-L1
PD-L1 is a protein that tumor cells can use to shield themselves from attack by the immune system. Testing for PD-L1 is performed by immunohistochemistry. In ovarian cancer, results are usually expressed as a Combined Positive Score (CPS), which counts the number of PD-L1-staining cells — including tumor cells and immune cells — relative to the total number of tumor cells. A CPS of 1 or higher is typically considered positive.
PD-L1 testing in ovarian cancer is most relevant in the setting of advanced or recurrent disease, where immunotherapy agents such as pembrolizumab may be considered alongside chemotherapy or as a later-line option. The role of PD-L1 as a predictive marker in ovarian cancer is still evolving, and a positive result alone does not guarantee a response to immunotherapy. Your oncologist will consider PD-L1 results alongside other clinical and molecular findings when discussing treatment options.
Folate receptor alpha (FOLR1)
Folate receptor alpha (also called FOLR1) is a protein found on the surface of some cancer cells that helps transport folate — a type of B vitamin — into the cell. Most normal adult tissues produce very little of this protein, but many ovarian cancers, particularly high-grade serous carcinomas, produce it in large amounts.
FOLR1 testing is performed by immunohistochemistry on tumor tissue. A tumor is considered FOLR1-positive if at least 75% of viable tumor cells show moderate-to-strong staining on the cell membrane (the cell’s outer surface). Patients with FOLR1-positive ovarian cancer may be eligible for treatment with mirvetuximab soravtansine (Elahere). This antibody-drug conjugate targets FOLR1 to deliver a cancer-killing drug directly to tumor cells. In clinical trials, mirvetuximab soravtansine demonstrated response rates of approximately 32% and a significant improvement in progression-free survival compared with chemotherapy in platinum-resistant, FOLR1-positive ovarian cancer.
For more information about biomarker testing in ovarian cancer, see the Biomarkers and Molecular Testing section.
Pathologic stage (pTNM)
Staging describes how far the cancer has spread in the body. For ovarian cancer, the pathologic stage is based on the TNM system developed by the American Joint Committee on Cancer (AJCC) and closely mirrors the FIGO (International Federation of Gynecology and Obstetrics) staging system used by gynecologic oncologists. The stage is made up of three components: T (how far the tumor has grown locally), N (whether it has spread to lymph nodes), and M (whether it has spread to distant organs). M stage is determined by imaging, not pathology, and is not assigned in the pathology report unless distant spread was sampled at surgery.
Tumor stage (pT)
- pT1 (FIGO Stage I) — Tumor is limited to one or both ovaries or fallopian tubes.
- pT1a — Tumor is inside one ovary or fallopian tube only; the outer surface (capsule) is intact, and no tumor cells are found in abdominal fluid.
- pT1b — Tumor involves both ovaries or fallopian tubes; capsule is intact, and no tumor cells are found in abdominal fluid.
- pT1c — Tumor is limited to one or both ovaries or fallopian tubes. Still, there has been capsule rupture, tumor on the outer surface, or cancer cells found in abdominal fluid or washings.
- pT2 (FIGO Stage II) — Tumor has spread beyond the ovaries or fallopian tubes into the pelvis.
- pT2a — Spread to the uterus, fallopian tubes, or ovaries (if not the site of origin).
- pT2b — Spread to other pelvic tissues such as the bladder or rectum.
- pT3 (FIGO Stage III) — Tumor has spread beyond the pelvis to the lining of the abdomen (peritoneum) or to regional lymph nodes.
- pT3a — Microscopic spread to the peritoneum outside the pelvis, with or without lymph node involvement.
- pT3b — Visible tumor deposits up to 2 cm on the peritoneum outside the pelvis, with or without lymph node involvement.
- pT3c — Visible tumor deposits larger than 2 cm outside the pelvis, or spread to the outer surface (capsule) of the liver or spleen, with or without lymph node involvement.
Note: Spread inside the substance of the liver or spleen (rather than only on their surface) is classified as M1 (Stage IVB).
Nodal stage (pN)
- pN0 — No cancer cells in regional lymph nodes.
- pN0(i+) — Only isolated tumor cells (measuring 0.2 mm or less) are found in the lymph nodes. Not counted as definitive nodal spread in all staging systems.
- pN1 — Cancer cells are found in regional lymph nodes.
- pN1a — Tumor deposits measuring up to 10 mm.
- pN1b — Tumor deposits measuring more than 10 mm.
What is the prognosis?
The prognosis for high-grade serous carcinoma of the ovary depends mainly on the stage at diagnosis, how much tumor can be removed at surgery (called residual disease), and specific biomarker results. Overall, high-grade serous carcinoma is a serious diagnosis — but outcomes have improved meaningfully over the past decade with the introduction of PARP inhibitor maintenance therapy.
Stage is the single most important prognostic factor. Five-year survival rates are approximately:
- Stage I — 80–90%. Very few patients are diagnosed at this stage.
- Stage II — 60–75%.
- Stage III — 30–50%. The majority of patients are diagnosed at this stage.
- Stage IV — 15–25%.
Additional factors associated with better outcomes include:
- No residual disease after surgery (complete cytoreduction) — Patients left with no visible tumor after surgery have significantly better survival than those with residual disease.
- BRCA mutation — Tumors with BRCA1 or BRCA2 mutations tend to respond better to platinum chemotherapy and are eligible for PARP inhibitor maintenance, which has been shown to extend progression-free survival significantly.
- HRD-positive status — Even in the absence of a BRCA mutation, HRD-positive tumors respond better to platinum-based treatment and may benefit from PARP inhibitors.
- Response to first-line chemotherapy — Patients whose tumors respond well to initial platinum-based chemotherapy tend to have better outcomes.
High-grade serous carcinoma frequently recurs after initial treatment, even after an excellent initial response. When recurrence happens more than six months after completing platinum chemotherapy, the cancer is called platinum-sensitive and is likely to respond to further platinum-based treatment. Recurrence within six months is called platinum-resistant and typically requires different therapies. Despite the high rate of recurrence, many patients live for many years with this diagnosis, and treatment options at recurrence continue to expand.
What happens after the diagnosis?
Treatment for high-grade serous carcinoma is planned by a multidisciplinary team that typically includes a gynecologic oncologist, a medical oncologist, a radiation oncologist, a pathologist, and a radiologist. Most patients will have a combination of surgery and chemotherapy.
Surgery — called cytoreductive surgery or debulking — aims to remove as much tumor as possible from the abdomen and pelvis. Achieving no visible residual disease is the goal. In most cases, surgery removes the ovaries, fallopian tubes, uterus, and omentum (called a total abdominal hysterectomy and bilateral salpingo-oophorectomy with omentectomy). Additional resections of involved bowel, peritoneum, or other structures may be required.
In some patients, chemotherapy is given before surgery (called neoadjuvant chemotherapy) to shrink the tumor and make surgery more effective. This is followed by interval debulking surgery, then further chemotherapy. In other patients, surgery is performed first, followed by chemotherapy. Your gynecologic oncologist will recommend the approach most likely to result in the best outcome for your situation.
First-line chemotherapy is typically carboplatin and paclitaxel, given intravenously, often with bevacizumab (Avastin), a drug that reduces the blood supply to the tumor. After completing chemotherapy, patients with BRCA mutations are typically offered PARP inhibitor maintenance therapy. Patients with HRD-positive tumors (including BRCA-mutated tumors) are also eligible for PARP inhibitor maintenance in combination with bevacizumab in some settings.
All patients with high-grade serous carcinoma should be referred to a genetic counselor to discuss whether germline BRCA testing is appropriate, regardless of whether the tumor test found a mutation. Genetic testing has important implications for family members.
Follow-up after treatment typically involves regular clinical assessments, CA-125 monitoring, and imaging when signs of potential recurrence appear. are present. Your oncology team will outline the follow-up schedule appropriate for your situation.
Questions to ask your doctor
- What stage is my ovarian cancer, and what does that mean for my treatment and prognosis?
- Has the tumor spread beyond the ovary to the peritoneum, lymph nodes, or other organs?
- Was the ovarian capsule intact, or did it rupture before or during surgery?
- Has BRCA testing been performed on my tumor tissue and on my blood, and what did each test show?
- Is my BRCA mutation germline (inherited) or somatic (acquired only in the tumor)? And should my family members be tested?
- Was HRD testing performed, and am I HRD-positive?
- Am I eligible for PARP inhibitor maintenance therapy, and if so, which drug would you recommend?
- Was FOLR1 testing performed, and does the result affect my treatment options?
- What were the MMR and PD-L1 results, and do they affect my treatment options?
- How much tumor remained after surgery, and how does that affect my prognosis?
- Should I be referred to a genetic counselor to discuss my BRCA results and their implications for my family?
- What follow-up schedule do you recommend after I complete treatment?
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