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Section 2 of 7

Author Information Introduction Cancer Antigen 125 Other Gynecologic Tumor Markers Markers For Response To Therapy And Relapse Pictures Bibliography

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Author Information Introduction Cancer Antigen 125 Other Gynecologic Tumor Markers Markers For Response To Therapy And Relapse Pictures Bibliography

Tumor markers indicate biological changes that signal the existence of malignancy in a host organism. These substances can usually be detected in elevated quantities in the blood, urine, or body tissues of patients with certain types of cancer. Tumor markers are produced by the tumor itself or by the body in response to the presence of cancer or certain benign conditions. Following the development of monoclonal antibodies, an array of new tumor markers has been discovered during the past 2 decades. Tumor markers can be used to (1) screen a healthy or high-risk population for the presence of cancer, (2) assist in confirming a diagnosis of cancer or of a specific type of cancer, (3) assist in determining a patient's prognosis, and (4) monitor the disease course in a patient in remission or in a patient who is undergoing surgery, radiation, or chemotherapy. Currently, tumor markers are primarily used to help assess tumor response to treatment and to check for recurrence.

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Cancer and Tumors Center Women's Health Center Breast Cancer Overview

Most studies focus on either endometrial or ovarian carcinoma. Other gynecologic malignancies (eg, cervical, vulvar, vaginal) have Breast Lumps and Pain a much smaller representation in the medical literature. Some Overview markers show promise as prognostic indicators. The following are important gynecologic tumor markers:

Breast SelfExam Cervical Cancer Overview

Cancer antigen 125 (CA125) Topoisomerase II Melan-A and inhibin-alpha Carbohydrate antigen 19-9

Ferritin Beta chorionic gonadotropin (hCG) Urinary gonadotropin fragment Carcinoembryonic antigen (CEA) Alpha-fetoprotein (AFP) Others o Tumor-associated trypsin inhibitor o Cyclin E o Lysophosphatidic acid o Insulinlike growth factorbinding protein-3 o OVX1 o Macrophage colony-stimulating factor

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Immunohistochemical markers useful or relevant in the differential diagnosis of gynecological lesions include the following:

Vulva and cervix o Paget disease versus superficial spreading melanoma - Anticytokeratin, S-100, homatropine methylbromide o Cervical intraepithelial neoplasia versus invasive carcinoma - Anticytokeratin smooth muscle actin (SMA), collagen type IV, CEA o Minimal-deviation endocervical adenocarcinoma versus benign endocervical glands - Blood group antigens o Endocervical adenocarcinoma versus endocervical microglandular hyperplasia - Human milk fat globule antigen-1 o Endocervical adenocarcinoma versus endometrial adenocarcinoma - Glial fibrillary acidic protein, keratin, vimentin, CEA, S-100 Uterine corpus o Endometrial carcinoma versus atypical hyperplasia Human milk fat globule antigen-1, human milk fat globule antigen-2, blood grouprelated antigens o Poorly differentiated endometrial carcinoma versus malignant mixed mesodermal tumor - Keratin, muscle-specific actin, SMA, myoglobin o Stromal sarcoma versus leiomyosarcoma - Keratin, vimentin, muscle-specific actin, SMA, desmin Ovaries o Surface epithelial carcinoma versus granulosa cell tumor - Vimentin, keratin o Nonmucinous carcinoma versus mucinous carcinoma - Keratin, vimentin, glial fibrillary acidic

protein, CA125, CEA, S-100, epithelial membrane antigen o Germ cell tumor versus carcinoma - Human placental alkaline phosphatase o Dysgerminoma versus embryonal carcinoma Keratin, AFP o Yolk sac tumor versus clear cell carcinoma - AFP, LeuM1 o Thecoma-fibroma versus leiomyoma - Vimentin, muscle-specific actin, SMA o Metastatic gastrointestinal carcinoma versus primary mucinous carcinoma - Keratin, CEA, glial fibrillary acidic protein Placenta o Partial mole versus complete mole - hCG, human placental lactogen, human placental alkaline phosphatase o Trophoblast versus decidual cell - Keratin, human placental lactogen, hCG Cytology o Carcinoma cells versus mesothelial cells - B72.3 o Benign cervical squamous cells versus high-grade cervical intraepithelial neoplasia - Blood group antigens

No marker is completely specific; therefore, diagnostic immunohistochemistry testing must be used in conjunction with morphologic and clinical findings. For excellent patient education resources, visit eMedicine's Cancer and Tumors Center and Women's Health Center. Also, see eMedicine's patient education articles Breast Cancer, Breast Lumps and Pain, Breast Self-Exam, and Cervical Cancer. CANCER ANTIGEN 125
Section 3 of 7

Author Information Introduction Cancer Antigen 125 Other Gynecologic Tumor Markers Markers For Response To Therapy And Relapse Pictures Bibliography

Approximately 90% of ovarian cancers are celomic epithelial carcinomas and contain a celomic epitheliumrelated glycoprotein designated CA125. CA125 can be localized in most serous, endometrioid, and clear cell ovarian carcinomas; mucinous tumors express this antigen less frequently. CA125 is also found in the epithelium of the fallopian tubes, endometrium, and uterine cervix. Ovarian carcinoma is the leading cause of death from gynecologic

malignancies. CA125 is an important tumor marker for the diagnosis, treatment, and follow-up care of patients with epithelial ovarian cancer and has been recommended for screening; however, CA125 may not lead to early diagnosis because it is not perfectly sensitive or specific for ovarian cancer. CA125 can be used clinically to determine response to treatment, relapse, and survival. Elevated CA125 levels can result from abdominal diseases other than ovarian cancer. Although CA125 is most consistently elevated in patients with epithelial ovarian cancer, it can be expressed in a number of gynecologic (eg, endometrium, fallopian tube) and nongynecologic (eg, pancreas, breast, colon, lung) cancers. CA125 levels are frequently elevated with tumor spread beyond the uterus and have been found highly sensitive in detecting extrauterine disease. Serum CA125 markers are primarily used to monitor the progress of ovarian cancer. An increase in CA125 levels during or after treatment is a strong predictor of future disease progression. A rapid decrease in CA125 levels during initial treatment correlates with longer progression-free intervals and survival. A CA125 level less than 15 U/mL after a standard 6-course treatment generally correlates with longer progression-free intervals, although it does not predict whether microscopic disease is present. A CA125 value greater than 35 U/mL after a standard 6-course chemotherapy treatment predicts the presence of disease. Disease progression may occur when CA125 values are stable. Standardized CA125 definitions have the potential of complementing or, in some cases, replacing current response definitions in a cost-effective fashion. The rate of CA125 decline during primary chemotherapy is an important independent prognostic factor. Persistent elevation of CA125 levels at the time of a second-look surgical surveillance procedure predicts residual disease with greater than 95% specificity. Rising CA125 values have preceded clinical detection of recurrent disease by at least 3 months in most studies. Given the modest activity of salvage chemotherapy, this information has not yet influenced survival rates. Rising CA125 levels during subsequent chemotherapy have been associated with progressive disease in more than 90% of cases. CA125 may serve as an effective surrogate marker for clinical response in phase II trials of new drugs. The measurement of CA125 levels, usually in combination with other modalities (eg, bimanual pelvic examination, transvaginal

ultrasonography) is a proposed method of early detection of ovarian cancer, which is the most promising application of this tumor marker. CA125 levels can help distinguish malignant and benign pelvic masses, which permits effective triage of patients for primary surgery. In addition, an algorithm has been developed that estimates the risk of ovarian cancer based on the level and trend of CA125 values. A major trial has been initiated using the risk of ovarian cancer algorithm to signal the need for transvaginal sonography and/or subsequent laparotomy. This trial can show improvement in survival rates by early detection. OTHER GYNECOLOGIC TUMOR MARKERS
Section 4 of 7

Author Information Introduction Cancer Antigen 125 Other Gynecologic Tumor Markers Markers For Response To Therapy And Relapse Pictures Bibliography

Topoisomerase II Topoisomerase II expression is detected in tumor samples by immunohistochemistry and has emerged as a promising, clinically relevant biomarker for survival in patients with advanced epithelial ovarian cancer. Melan-A and inhibin-alpha The recent availability of markers of ovarian stroma, including Melan-A and inhibin-alpha, has provided a means for the positive identification of ovarian stromal tumors, which can manifest in a myriad of histological appearances. Carbohydrate antigen 19-9 Serum carbohydrate antigen 19-9 levels are elevated in up to 35% of patients with endometrial cancer and can be used in a follow-up evaluation of patients with mucinous borderline ovarian tumors. Measurement of serum tumor markers in the follow-up care of these patients may lead to earlier detection of recurrence in only a very small proportion of patients; the clinical value of earlier detection of recurrence remains to be established. Carbohydrate antigen is not specific for ovarian cancer. Cancer antigen 15-3 Cancer antigen 15-3 is most useful when following the course of treatment in women with breast cancer, especially advanced breast

cancer. Levels are rarely elevated in women with early-stage breast cancer. Patients with cancers of the ovary, lung, or prostate may also have elevated cancer antigen 15-3 levels. In addition, increased levels may be associated with noncancerous conditions, including benign breast disease, benign ovarian disease, endometriosis, pelvic inflammatory disease, and hepatitis. Pregnancy and lactation can also cause elevated levels of this marker. Cancer antigen 27-29 Elevated cancer antigen 27-29 levels are associated with cancers of the colon, stomach, kidney, lung, ovary, pancreas, uterus, and liver. First-trimester pregnancy, endometriosis, ovarian cysts, benign breast disease, kidney disease, and liver disease are noncancerous conditions that are also associated with increased cancer antigen 27-29 levels. Beta human chorionic gonadotropin Beta hCG is expressed in human fetal tissue and cancer cells of various histologic types. It is degraded to the beta-core fragment, which is concentrated in urine and is also known as urinary gonadotropin peptide. Urinary gonadotropin fragment and lipidassociated sialic acid levels are elevated in up to 60% of patients with endometrial cancer. Increased levels of hCG occur in patients with choriocarcinoma of the uterus, embryonal carcinomas, polyembryomas, mixed cell tumors, and, less commonly, dysgerminomas. Both hCG and hPL are the most useful markers for trophoblastic disease. Both hCG and hPL can be localized in syncytiotrophoblasts of partial and complete hydatidiform moles. The intensity and pattern of reactivity for these antigens differ in partial and complete moles. Gestational choriocarcinomas demonstrate variable but positive staining results for hCG and hPL. The hPL immunostaining differentiates placental-site trophoblastic tumors from choriocarcinomas. The use of hCG is not limited to trophoblastic diseases because it has been localized in a wide array of nontrophoblastic gynecologic neoplasms. MARKERS FOR RESPONSE TO THERAPY AND RELAPSE
Section 5 of 7

Author Information Introduction Cancer Antigen 125 Other Gynecologic Tumor Markers Markers For Response To Therapy

And Relapse Pictures Bibliography

The following tumor markers are helpful in assessing response to chemotherapy and in determining relapse when monitoring patients with complete remission. Squamous cell carcinoma antigen The squamous cell carcinoma antigen level can be increased in patients with epidermoid carcinoma of the cervix, benign tumors of epithelial origin, and benign skin disorders. Carcinoembryonic antigen Most sweat gland tumors of the vulva stain positively for CEA. In most instances, the reaction for CEA occurs in cells that line cysts, form glands, or are arranged around a lumen. The reaction for CEA does not differentiate eccrine from apocrine adnexal tumors. In patients with vaginal adenosis, both surface columnar epithelium and glands may show focal cytoplasmic membrane staining for CEA. As the columnar cells are gradually replaced by the process of squamous metaplasia, CEA positivity may be observed in the cytoplasm of metaplastic cells. Malignant vulvar tumors of sweat gland origin stain positively for CEA. Both in situ and invasive adenocarcinomas underlying extramammary Paget disease of the anogenital area express CEA. CEA is also demonstrable in Paget cells in metastatic sites such as lymph nodes. CEA is present in most urothelial adenocarcinomas of the female urethra. CEA levels are elevated in up to 35% of patients with endometrial cancer. CEA immunohistochemistry cannot distinguish between benign and malignant glandular proliferations of the uterine cervix; therefore, CEA staining is of no value in the differential diagnosis of endocervical and endometrial adenocarcinomas. Most epithelial neoplasms of the ovary also express CEA. The neoplasms include, with decreasing intensity and frequency, Brenner, endometrioid, clear cell, and serous tumors. CEA is frequently present in patients with cancer that has metastasized to the ovary because the primary cancer is generally mammary or gastrointestinal in origin and these tumors frequently contain CEA. Alpha-fetoprotein AFP is a normal fetal serum protein synthesized by the liver, yolk sac, and gastrointestinal tract that shares sequence homology with albumin. AFP is a major component of fetal plasma, reaching a peak concentration of 3 mg/mL at 12 weeks of gestation. Following birth, AFP rapidly clears from the circulation because its half-life is 3.5 days. AFP concentration in adult serum is less than 20 ng/mL. Most endodermal sinus tumors of the ovary express AFP. AFP is present within the cytoplasm of tumor cells and in the characteristic hyalin globules observed in the endodermal sinus tumor. AFP is also expressed by ovarian embryonal cell carcinoma,

immature teratomas, and polyembryomas. Lysophosphatidic acid Lysophosphatidic acid stimulates cancer cell proliferation, intracellular calcium release, and tyrosine phosphorylation, including mitogen-activated protein kinase activation. Lysophosphatidic acid has been shown to be a multifunctional signaling molecule in fibroblasts and other cells. It has been found in the ascitic fluid of patients with ovarian cancer and is associated with ovarian cancer cell proliferation. Further studies are needed to determine the role of these markers. MIB1-determined tumor growth fraction has recently been studied as an additional tool for the decision of adjuvant therapy in patients with very early stages of ovarian carcinomas. In one study, MIB1 predicted tumor recurrences in 84% of the ovarian cancers