Ovarian Cancer

Key Points

Use of Tumor Markers in Pelvic Masses: Cancer Antigen 125 (CA-125) and Human Epididymis Protein (HE4)

Biology

  • CA-125 – glycoprotein antigen expressed in tissue derived from coelomic epithelial cells (ovary, fallopian tube, peritoneum, pericardium, colorectal, kidney, stomach)
    • Frequency of elevation correlates with clinically detected stage of cancer, tumor burden, and type of tumor
  • HE4 – secreted protein expressed in most epithelial ovarian tumors
    • Marker of relapse
    • Improves specificity of CA-125 if used in conjunction

Uses

  • In general, the combination of CA-125 and HE4 provides the highest sensitivity and specificity
  • Tumor markers in ovarian cancer and pelvic masses
Ovarian Cancer

Screening

Diagnosis

  • Most ovarian tumors are epithelial and secrete CA-125 and HE4
    • In ~50% of patients, these markers do not increase early enough to be useful for detecting early stage ovarian cancer (NCCN 2014)
    • In small number of tumors, markers are not expressed    
  • Increased survival rates associated with optimal surgical debulking in initial tumor surgery
    • Best performed at earlier stages 
  • ACOG (2011) recommends referral to a gynecologic oncologist in the following cases
    • Premenopausal women with CA-125 levels >200 U/mL
    • Postmenopausal women with CA-125 levels >35 U/mL

Monitoring

  • Useful in monitoring therapy and for recurrence if CA-125 and/or HE4 level is initially elevated
  • Rising levels accurately predict relapse
Pelvic Mass

Premenopausal

  • Cannot use markers to differentiate benign from malignant mass
  • False elevations of CA-125 occur in many benign gynecologic diseases (eg, endometriosis)
  • HE4 more specific – its use alone or in combination with CA-125 is not recommended to rule out malignancy

Postmenopausal

  • Useful in differential diagnosis of pelvic mass
  • Decreased false-positive rate if both tests are performed
  • CA-125 >65 U/mL highly suggestive of malignancy
  • Recent studies, using the Risk of Ovarian Malignancy Algorithm (ROMA) that combine CA-125 and HE4 concentrations to calculate risk, have produced conflicting reports
    • HE4 in combination with CA-125 appears more sensitive than CA-125 alone

Diagnosis

Indications for Testing

  • Individual with suspected ovarian cancer

Laboratory Testing

  • Biomarkers
    • Epithelial cell tumors
      • Beta-hCG – consider this test in premenopausal females to rule out pregnancy
      • CA-125
        • Not recommended as a single initial diagnostic test (although results >65 U/mL are highly suggestive of malignancy)
        • Recommended differential diagnosis of suspicious pelvic mass in postmenopausal females
      • HE4 – combining with CA-125 decreases false positives
      • Inhibin – complements CA-125
        • Best performance in mucinous subtype
      • Other markers currently available are not generally as useful
    • Granulosa-theca tumors
      • CA-125 – frequently normal (not useful if normal)
      • Inhibin – alpha and beta (beta usually higher than alpha)
        • Total inhibin – highly sensitive
      • Estradiol – often elevated
    • Germ cell tumors
      • CA-125 – not useful (usually normal)
      • Beta-hCG – elevated
      • Alpha fetoprotein (AFP) – elevated
      • Neuron-specific enolase (NSE) – elevated
      • Lactate dehydrogenase (LD) – elevated

Histology

  • Surgical biopsy to determine if ovarian mass is malignant (with planned surgical debulking if malignant)
    • Avoid percutaneous biopsy – can cause tumor spillage into the pelvis
    • All tumors require histologic confirmation for diagnosis
  • Immunohistochemistry
    • Epithelial
      • Serous
        • HGSC
          • (+) p53, WT-1, p16, ER
        • LGSC
          • (+) WT-1, ER
      • Mucinous
        • (+) CK 7, CK 20 (weak, focal), CDX2 (weak, focal), SMAD4, DPC4
        • (-) ER, WT-1 (not diffusely positive), beta-catenin-1, p16
      • Endometrioid
        • (+) ER, PR (nuclear), beta-catenin-1, vimentin, CK 7
        • (+) p53 in some high-grade endometrioid – most lack p53, p16
        • (-) WT-1 (not diffusely positive), calretinin, inhibin, CK 20, CEA (monoclonal or polyclonal)
      • Clear cell
        • (+) HNFI-beta, beta-catenin-1
        • (-) ER, WT-1 – typically lack p53 unless high-grade
      • Transitional cell
        • (+) WT-1, ER, p53
        • (-) p53 – typically lack p53 unless high-grade
    • Granulosa/Sertoli – (+) inhibin, WT-1, calretinin
    • Germ cell – (+) CA-125, inhibin, AFP, beta-hCG
  • Molecular testing based on histology
    • High-grade serous carcinoma (HGSC) – BRCA1 or BRCA2 gene mutations common
      • BRCA1 and BRCA2 testing is recommended for all of these patients (NCCN, 2014)
    • Low-grade serous carcinoma (LGSC) – BRAF or KRAS gene mutations
    • Mucinous – KRAS gene mutations common
    • Endometrioid – CTNNB1 and PTEN gene mutations common
    • Clear cell – lacks BRCA1 or BRCA2 gene mutations
    • Transitional cell
      • If lacking Brenner component – BRCA1 or BRCA2 gene mutations common
    • Granulosa cell – FOXL2 gene mutations

Imaging Studies

  • Ultrasound
    • Transvaginal sonography (TVS) followed by CT/MRI if suspicious TVS findings

Prognosis

  • p53 overexpression
    • Correlates with poor survival, propensity for recurrence, and distant recurrence
  • RAS dysregulation in serous subtype
    • Associated with poor prognosis in patients with incomplete response to platinum-based therapy
  • Beta-catenin-1 dysregulation in serous subtype
    • Associated with poor prognosis in patients with incomplete response to platinum-based therapy
  • EGFR overexpression
    • Associated with platinum resistance and poor prognosis
  • HER2 expression – in only 10% of patients
    • Correlates with poor survival
  • MMP-9 overexpression
    • Associated with poor prognosis

 Differential Diagnosis

Screening

  • Routine screening in general population is not currently recommended by any professional society
  • Screening for specific syndromes
    • BRCA – ovarian cancer risk >50%
      • If patient chooses not to undergo total abdominal hysterectomy with bilateral salpingo-oophorectomy, begin screening at age 35, or 5-10 years before earliest age of diagnosis of ovarian cancer in family
        • See NCCN Genetic/Familial High-Risk Assessment (Breast and Ovarian Oncology) 2014 screening guidelines
        • Concurrent TVS and CA-125 – every 6 months
          • TVS – preferably day 1-10 of menstrual cycle in premenopausal women
          • CA-125 – preferably after day 5 of menstrual cycle in premenopausal women
    • Lynch syndrome (HNPCC) – ovarian cancer risk 10%
      • TVS – beginning at 30-35 years (for endometrial cancer screening)
      • CA-125 – unproven efficacy due to inadequate trials
  • Hereditary breast and ovarian cancer (HBOC) genetic testing
    • Symptoms in women with any of the following
      • Breast cancer diagnosed by 45 yrs
      • Ovarian cancer
      • Two primary breast cancers, first diagnosed by 50 yrs
      • Breast cancer diagnosed by 50 yrs with ≥1 family members with breast cancer
      • Triple negative breast cancer diagnosed by 60 yrs
      • Breast cancer at any age with ≥1 family members with breast cancer diagnosed by 50 yrs
      • Breast cancer diagnosed at any age with ≥2 family members from the same side diagnosed with breast cancer at any age
      • Breast cancer at any age with ≥1 family members with ovarian cancer
      • Breast cancer diagnosed at any age with ≥2 family members with pancreatic or prostate cancer
      • Breast cancer diagnosed at any age and male family member with breast cancer
      • Breast cancer at any age and Ashkenazi Jewish ancestry
      Based on family history (in asymptomatic patient)
      • For women with no Ashkenazi Jewish ancestry and family history of any of the following on the same side of the family
        • Two first-degree relatives diagnosed with breast cancer, one diagnosed at 50 yrs or younger
        • Three or more first-degree or second-degree  relatives diagnosed with breast cancer regardless of their age
        • A combination of first- and second-degree relatives diagnosed with breast cancer and ovarian cancer (one cancer type per person)
        • A first-degree relative with bilateral breast cancer
        • A combination of two or more first- or second-degree relatives diagnosed with ovarian cancer regardless of age at diagnosis
        • A first- or second-degree relative diagnosed with both breast and ovarian cancer regardless of age at diagnosis
        • Breast cancer diagnosed in a male relative
      • For women with Ashkenazi Jewish ancestry and family history of any of the following
        • First-degree relative diagnosed with breast or ovarian cancer
        • Two second-degree relatives on the same side of the family diagnosed with breast or ovarian cancer
    • For individuals with a family history of a known pathogenic mutation previously identified in a relative – perform targeted mutation testing

Monitoring

  • Epithelial
    • CA-125
      • Assess patient response to chemotherapy, detect early relapse, and predict prognosis
        • Absolute serum value of CA-125 before third cycle of chemotherapy – most important factor for predicting progression at 12 months
      • Suggested monitoring – every 2-4 months for the first 2 years
        • Persistent postoperative elevation suggests poor prognosis
    • HE4
      • Relatively new marker in ovarian cancer monitoring
      • Useful because not all patients with ovarian cancer have elevated CA-125 levels
      • May be complementary when used with CA-125 for monitoring
      • ≥25% change is considered significant
    • Inhibin – most useful in monitoring of mucinous subtype tumors
    • Other emerging markers, such as osteopontin, show promise but cannot be recommended
  • Stromal tumors (including granulosa, granulosa-theca, and Sertoli-Leydig tumors)
    • Inhibin levels – increased levels parallel tumor recurrence
  • Germ cell
    • Alpha fetoprotein (AFP), beta-hCG, lactate dehydrogenase (LD)
      • Expect decrease after surgery
      • Increasing levels may signal recurrence

Clinical Background

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the U.S. and the fifth most common cause of cancer mortality in U.S. women.

 Epidemiology

  • Incidence
    • Ovarian cancer – ~22,000 new cases and >14,000 deaths annually (NCCN, 2014)
      • Epithelial subtype – 40/100,000 for postmenopausal women
      • ~90% of malignant tumors
    • Incidence increases with age
      • 50-54 years – 20.4/100,000
      • 65-69 years – 38/100,000
      • 75-80 years – 48/100,000
  • Age – median is 63 years
    • 90% of women with ovarian cancer are >40 years
  • Sex

 Genetics

  • TP53 gene mutations
    • Present in ~50-80% of ovarian carcinomas
    • Correlates with high-grade and advanced state
    • High-grade serous carcinomas are the most common tumor in this group
  • KRAS gene mutations
    • Characteristic of both low-grade serous and mucinous carcinomas
  • BRAF gene mutations
    • Typical of low-grade serous carcinomas
  • FOXL2 gene mutation c.402C>T
    • Present in 97% of granulosa cell tumors in adults and 10% of juvenile tumors
  • Hereditary gene mutations
    Gene Symbol

    Inheritance

    Cancer Association

    ATMADBreast
    BARD1ADBreast, neuroblastoma
    BRCA1ADBreast, ovarian, fallopian, peritoneal, pancreatic, prostate
    BRCA2ADBreast, ovarian, fallopian, peritoneal, pancreatic, prostate, gallbladder, gastric, melanoma
    BRIP1ADBreast, ovarian
    CDH1ADGastric, breast, prostate
    CHEK2ADBreast, colorectal, prostate
    EPCAMADColorectal, ovarian
    MEN1ADGlucagonomas, gastrinomas, VIPomas, thymic, bronchial, gastric, breast
    MLH1ADOvarian, colorectal, endometrial, bladder, kidney
    MSH2ADOvarian, colorectal, endometrium, bladder, kidney
    MSH6ADOvarian, colorectal , endometrium, bladder, kidney
    MUTYHAR, ADColorectal (AR), gastric, breast, duodenal, endometrium (AD)
    NBNADBreast, ovarian
    PALB2ADBreast, pancreatic
    PTENADThyroid, breast, endometrial
    RAD51CADBreast, ovarian
    RAD51DADBreast, ovarian
    STK11ADColorectal, pancreatic, breast, ovarian
    TP53ADBreast, ovarian, brain, soft tissue and osteosarcomas, gastrointestinal, leukemia, lymphoma, adrenocortical carcinoma
    AD = autosomal dominant; AR = autosomal recessive

 Risk Factors

  • Increased risk associated with
    • Family history of breast or ovarian cancer (hereditary breast or ovarian cancer [HBOC])
      • Associated with BRCA1, BRCA2, and Lynch Syndrome II
        • Higher probability of BRCA1 and BRCA2 gene mutations in Ashkenazi Jews
        • 10-15% of ovarian cancers are caused by BRCA1 or BRCA2 mutations
    • Nulliparity
    • Older age at first birth (≥35 years)
    • Early menarche
    • Hormone therapy
    • Pelvic inflammatory disease (PID), in vitro stimulation may increase risk
  • Decreased risk (30-60%) associated with
    • Oral contraceptive use
    • Pregnancy and first birth at young age (≤25 years)
    • Multiparity
    • Lactation (>18 months)
    • History of tubal ligation/hysterectomy
    • Early menopause/late menarche

 Pathophysiology

  • Malignant transformation of the Müllerian epithelium on the ovarian surface or Müllerian inclusion cysts in the ovarian cortex
    • Some high-grade serous carcinomas likely represent spread from a primary tumor arising in the distal fallopian tube
  • Often spreads early to the contiguous peritoneal mesothelium
    • Spread follows the flow of peritoneal fluid
  • Types
    • Epithelial (85-95%)
      • WHO classification of epithelial tumors 
        • Serous
        • Mucinous
        • Endometrioid
        • Clear cell
        • Transitional cell and squamous types (rare)
    • Stromal (5-8%)
      • Granulosa-theca
      • Sertoli-Leydig
    • Germ cell (3-5%)
      • Dysgerminoma
      • Endodermal sinus
      • Immature teratoma
      • Embryonal
    • Metastasis to ovaries
      • Krukenberg tumor

 Clinical Presentation

  • Epithelial cell tumors
    Epithelial Cell Tumors
    • Symptoms – usually nonspecific; most patients present with stage III or IV disease
    • Abdominal symptoms
      • Abdominal fullness
      • Dyspepsia
      • Early satiety
      • Bloating
      • Pelvic pain
    • Physical findings
      • Ascites
      • Pleural effusions
      • Umbilical mass (Sister Mary Joseph nodule)
      • Ovarian mass
    • Unusual findings
    Stromal cell tumors
    Stromal Cell Tumors
    • Granulosa-theca
      • Juvenile
        • Suspect this tumor in females <20 years with adnexal mass
        • Precocious sexual development in prepubertal female
        • Rare virilization
        • Abdominal pain (predominant symptom)
      • Adult
        • Abdominal pain, increasing girth (predominant symptoms)
        • Premenopausal – hyperestrogenism, menstrual irregularities
        • Postmenopausal – abnormal uterine bleeding, breast tenderness
    • Sertoli-Leydig – virilization common
    Germ cell tumors
    Germ Cell Tumors
    • Frequently asymptomatic
    • Abdominal pain, increasing girth (predominant symptoms)
    • Postmenopausal vaginal bleeding

Prevention

  • In patients with known BRCA1 or BRCA2 gene mutation who have completed childbearing, bilateral salpingo-oophorectomy dramatically reduces risk for tubo-ovarian cancer
    • Small risk will still exist for primary peritoneal serous carcinoma

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Cancer Antigen 125 0080462
Method: Quantitative Electrochemiluminescent Immunoassay

Do not use as a single diagnostic test – adjunct test for evaluation of ovarian mass

Monitor (if initially elevated) epithelial cell tumor – combine with HE4 testing for fewer false positives

Adjunct test for distinguishing benign from malignant pelvic mass, particularly in postmenopausal women

Also useful for early detection of ovarian cancer in high-risk hereditary syndromes (eg, BRCA1 and BRCA2)

Not recommended for screening general population for ovarian cancer

Elevated in other gynecological conditions

Higher rate of false positives than HE4

Patients with confirmed ovarian carcinoma may have pretreatment CA-125 value in the same range as healthy individuals

Test values for CA-125 are not interchangeable between different laboratories or test platforms – sequential monitoring should be performed at the same laboratory

 
Human Epididymis Protein 4 (HE4) 2003020
Method: Quantitative Enzyme Immunoassay

Do not use as a single diagnostic test – adjunct test for evaluation of ovarian mass

Monitor (if initially elevated) epithelial cell tumor – combine with CA-125 testing for fewer false positives

Not recommended for screening general population for ovarian cancer

Not recommended for monitoring patients with known mucinous or germ cell subtype

 
Inhibin B 0070413
Method: Quantitative Enzyme-Linked Immunosorbent Assay

Evaluate suspected granulosa cell tumor

Monitor mucinous subtype tumor – combine with CA-125 testing

   
Estradiol, Adult Premenopausal Female, Serum or Plasma 0070045
Method: Quantitative Chemiluminescent Immunoassay

Evaluate suspected granulosa cell tumor

   
Alpha Fetoprotein, Serum (Tumor Marker) 0080428
Method: Quantitative Chemiluminescent Immunoassay

Evaluate suspected germ cell tumor

Monitor germ cell tumor during treatment (if level initially elevated)

   
Neuron Specific Enolase 0098198
Method: Quantitative Enzyme-Linked Immunosorbent Assay

Evaluate suspected germ cell tumor

   
Lactate Dehydrogenase, Serum or Plasma 0020006
Method: Quantitative Enzymatic

Evaluate suspected germ cell tumor

Use for problematic ovarian tumor identification

   
Beta-hCG, Quantitative (Tumor Marker) 0070029
Method: Quantitative Electrochemiluminescent Immunoassay
Evaluate suspected germ cell tumor

Cannot be interpreted as absolute evidence of the presence or absence of malignant disease

Result not interpretable as a tumor marker in pregnant females

Results obtained with different test methods or kits cannot be used interchangeably

 
Breast and Ovarian Hereditary Cancer Panel, Sequencing and Deletion/Duplication, 20 Genes 2012026
Method: Massive Parallel Sequencing/Exonic Oligonucleotide-based CGH Microarray

Preferred first-tier genetic test for confirmation of hereditary breast and ovarian cancer (HBOC) syndrome

Highest detection rate for HBOC syndrome but also highest likelihood of identifying variants of unknown significance

Clinical sensitivity – unknown

Analytical sensitivity and specificity of sequencing – 99% and 96%, respectively

Analytical sensitivity and specificity of CGH – 99%

Deep intronic and regulatory mutaitons, breakpoints for large deletions/duplications, sequence changes in EPCAM (exons 11-15 of CHEK2 will not be evaluated with the exception of the c.1100delC mutation), and deletions/duplications (exon 1 in CDH1, MSH2, and RAD51D; exons 4,6, 7 in STK11; exon 8 in PTEN; exon 12 in ATM) will not be determined or evaluated

Small deletions or insertions may not be detected

Diagnostic errors can occur due to rare sequence variations

 
Breast and Ovarian Hereditary Cancer Syndrome (BRCA1 and BRCA2) Sequencing and Deletion/Duplication 2011949
Method: Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification

Acceptable first-tier genetic test for confirmation of HBOC

Only the BRCA1 and BRCA2 genes are assayed

Clinical sensitivity – ~20-60% sensitivity for HBOC syndrome

Analytical sensitivity and specificity of sequencing – 99% and 96%, respectively

Rare diagnostic errors can occur due to primer or probe site mutations

Regulatory region mutations and deep intronic mutations will not be detected

Genes causing HBOC syndrome, other than BRCA1 and BRCA2, are not tested

Deletion/duplication breakpoints will not be determined

 
Ashkenazi Jewish (BRCA1 and BRCA2) 3 Mutations 2011958
Method: Polymerase Chain Reaction/Fragment Analysis

Predictive or diagnostic testing for heritable predisposition for breast or ovarian cancer in adults of Ashkenazi Jewish descent only

Clinical sensitivity – 97% for BRCA1 and BRCA2 mutations in Ashkenazi Jewish individuals

Detection rate of <1% for BRCA1 and BRCA2 mutations in individuals who are not of Ashkenazi Jewish descent

BRCA1 and BRCA2 gene mutations, other than those targeted, will not be detected

Rare diagnostic errors may occur due to primer site mutations

 
p53 with Interpretation by Immunohistochemistry 0049250
Method: Immunohistochemistry

Aid in histologic diagnosis of ovarian cancer

Stained and resulted by ARUP

   
Wilms Tumor (WT-1), N-terminus by Immunohistochemistry 2004184
Method: Immunohistochemistry

Aid in histologic diagnosis of ovarian cancer

Stained and returned to client pathologist; consultation available if needed

   
p16 by Immunohistochemistry 2004064
Method: Immunohistochemistry

Aid in histologic diagnosis of ovarian cancer

Stained and returned to client pathologist; consultation available if needed

   
Estrogen/Progesterone Receptor with Interpretation by Immunohistochemistry 0049210
Method: Immunohistochemistry

Aid in histologic diagnosis of ovarian cancer

Stained and resulted by ARUP

   
Cytokeratin 7 (CK 7) by Immunohistochemistry 2003854
Method: Immunohistochemistry

Aid in histologic diagnosis of ovarian cancer

Stained and returned to client pathologist; consultation available if needed

   
Cytokeratin 20 (CK 20) by Immunohistochemistry 2003848
Method: Immunohistochemistry

Aid in histologic diagnosis of ovarian cancer

Stained and returned to client pathologist; consultation available if needed

   
CDX2 by Immunohistochemistry 2003821
Method: Immunohistochemistry

Aid in histologic diagnosis of ovarian cancer

Stained and returned to client pathologist; consultation available if needed

   
Beta-Catenin-1 by Immunohistochemistry 2003454
Method: Immunohistochemistry

Aid in histologic diagnosis of ovarian cancer

Stained and returned to client pathologist; consultation available if needed

   
Vimentin by Immunohistochemistry 2004181
Method: Immunohistochemistry

Aid in histologic diagnosis of ovarian cancer

Stained and returned to client pathologist; consultation available if needed

   
Calretinin by Immunohistochemistry 2003490
Method: Immunohistochemistry

Aid in histologic diagnosis of ovarian cancer

Stained and returned to client pathologist; consultation available if needed

   
Inhibin by Immunohistochemistry 2003969
Method: Immunohistochemistry

Aid in histologic diagnosis of ovarian cancer

Stained and returned to client pathologist; consultation available if needed

   
Carcinoembryonic Antigen, Monoclonal (CEA M) by Immunohistochemistry 2003824
Method: Immunohistochemistry

Aid in histologic diagnosis of ovarian cancer

Stained and returned to client pathologist; consultation available if needed

   
Carcinoembryonic Antigen, Polyclonal (CEA P) by Immunohistochemistry 2003827
Method: Immunohistochemistry

Aid in histologic diagnosis of ovarian cancer

Stained and returned to client pathologist; consultation available if needed

   
Cancer Antigen 125 by Immunohistochemistry 2003478
Method: Immunohistochemistry

Aid in histologic diagnosis of ovarian cancer

Stained and returned to client pathologist; consultation available if needed

   
Sal-like 4 (SALL4) by Immunohistochemistry 2005432
Method: Immunohistochemistry

Aid in histologic diagnosis of ovarian cancer

Stained and returned to client pathologist; consultation available if needed

   
Smad4 by Immunohistochemistry 2006403
Method: Immunohistochemistry

Stained and returned to client pathologist; consultation available if needed

   
PAX8 by Immunohistochemistry 2010787
Method: Immunohistochemistry

Distinguish ovarian cancer from breast cancer

Stained and returned to client pathologist for interpretation; consultation available if required

   
PD-L1 by Immunohistochemistry 2011158
Method: Immunohistochemistry

Aid in histologic diagnosis of lung cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
EGFR Mutation Detection by Pyrosequencing 2002440
Method: Polymerase Chain Reaction/Pyrosequencing

Prognostication in ovarian cancer

HER2/neu Quantitative by ELISA 2004672
Method: Quantitative Enzyme-Linked Immunosorbent Assay

Prognostication in ovarian cancer

KRAS Mutation Detection 0040248
Method: Polymerase Chain Reaction/Pyrosequencing

Prognostication in ovarian cancer

PTEN-Related Disorders (PTEN) Deletion/Duplication 2002726
Method: Polymerase Chain Reaction/Multiplex Ligation-dependent Probe Amplification

Prognostication in ovarian cancer

Solid Tumor Mutation Panel by Next Generation Sequencing 2007991
Method: Massively Parallel Sequencing

Prognostication in ovarian cancer

For a full list of the targeted regions of the above genes, click here

Breast and Ovarian Hereditary Cancer Syndrome (BRCA1 and BRCA2) Sequencing 2011954
Method: Polymerase Chain Reaction/ Sequencing

Up to 90% sensitivity for BRCA1 and BRCA2 mutations

Breast and Ovarian Hereditary Cancer Syndrome (BRCA1 and BRCA2) Deletion/Duplication 2011915
Method: Multiplex Ligation-dependent Probe Amplification

This is a second tier test and REQUIRES PERMISSION from ARUP genetic counselor before ordering

Order if no mutation detected by sequencing

Clinical sensitivity – ~10% for BRCA1 and BRCA2 mutations

Use to test for known familial BRCA1 or BRCA2 large deletions/duplications

Cancer Panel, Hereditary, Sequencing and Deletion/Duplication, 47 Genes 2012032
Method: Massive Parallel Sequencing/Exonic Oligonucleotide-based CGH Microarray

Preferred panel for confirming a diagnosis of a hereditary cancer with personal or family history consistent with features of more than one cancer syndrome

Cancer Panel, Hereditary, Deletion/Duplication, 46 Genes 2010757
Method: Exonic Oligonucleotide-based CGH Microarray

Use to test known familial deletions/duplications in one of the 46 genes on the panel