Immunohistochemistry (IHC) in Cancer

Tumor markers are molecules whose levels are considered as signals, symbols, or representatives of tumor cells, and increased in cancerous conditions. Normal cells express most of the tumor markers like tumor cells. By present, most tumor markers are found to be proteins, and some patterns of gene expression and DNA changes are also considered to be tumor markers. More than 20 tumor markers have been developed for clinical use. One kind of cancer is normally featured with one or more tumor markers. According to immunohistochemistry (IHC) visualized tumor markers such as enzymes, oncogenes, tumor-specific antigens, tumor suppressor genes and tumor proliferation markers, doctors can efficiently predict oncogenesis and diagnose a cancer as benign or malignant, determine the stage and the grade of a cancer.

Immunohistochemistry in Breast Cancer

Immunohistochemistry is playing an increasing role in the modern pathology of breast disease. Some of the diagnostic uses of IHC include differentiating UDH from ADH/LG-DCIS, ruling out microinvasion, distinguishing invasive carcinoma from pseudoinvasive lesions, identifyingbreast cancer histologic subtype and molecular phenotype, and confirming the breast as the primary site in metastatic carcinoma. In addition, immunohistochemical markers are useful for estimating prognosis and predicting therapy response. The best approach to the use of immunohistochemical markers is to couple them with standard hematoxylin-eosin histology and to use panels of markers.

Reference: Application of Immunohistochemistry to Breast Lesions, I-Tien Yeh, MD; Carolyn Mies, MD.

Immunohistochemistry in Lung Cancer

Immunohistochemistry represents an important complementary tool for the routine diagnosis of lung cancer and for the identification of the different histological types and prognostic factors. Its purpose is to categorize patients in order to ensure appropriate and specific treatment, as well as to identify tumors at higher risk of recurrence and fatal outcomes. The essential immunohistochemistry panel recommended for the diagnosis and prognosis includes expression of the following markers: CK7; CK20; COX-2; TTF-1, chromogranin; synaptophysin, CD56; PSA; CA125; p53; c-erbB-2; MMP-9; and VEGF.

Reference: Role of immunohistochemistry in the diagnosis of lung cancer, Vera Luiza Capelozzi.

Immunohistochemistry in Prostate Cancer

The use of IHC as an auxiliary in the diagnosis of adenocarcinoma is a common practice in uropathology, and the use of antibodies against p63 and high molecular weight cytokeratin has been recommended as adjuncts in confirming prostatic carcinoma in doubtful cases. Although basal cell markers, such as 34βE12 and p63 antibodies are useful for identifying basal cells, several benign mimickers of PC, such as atrophy, atypical adenomatous hyperplasia, nephrogenic adenoma, and mesonephric hyperplasia, can stain negatively with these markers. In addition, with patients being submitted to prostate biopsy with lower PSA levels and with larger numbers of cores being taken in each biopsy session, concern that patients are being overtreated is common.

Reference: The Use of Immunohistochemistry for Diagnosis of Prostate Cancer, Katia R. M. Leite, et al.

Cancer markers

ALK gene rearrangements

Cancer types: Non-small cell lung cancer and anaplastic large cell lymphoma
Tissue analyzed: Tumor
How used: To help determine treatment and prognosis

Alpha-fetoprotein (AFP)

Cancer types: Liver cancer and germ cell tumors
Tissue analyzed: Blood
How used: To help diagnose liver cancer and follow response to treatment; to assess stage, prognosis, and response to treatment of germ cell tumors

Beta-2-microglobulin (B2M)

Cancer types: Multiple myeloma, chronic lymphocytic leukemia, and some lymphomas
Tissue analyzed: Blood, urine, or cerebrospinal fluid
How used: To determine prognosis and follow response to treatment

Beta-human chorionic gonadotropin (Beta-hCG)

Cancer types: Choriocarcinoma and testicular cancer
Tissue analyzed: Urine or blood
How used: To assess stage, prognosis, and response to treatment

BCR-ABL fusion gene

Cancer type: Chronic myeloid leukemia
Tissue analyzed: Blood and/or bone marrow
How used: To confirm diagnosis and monitor disease status

BRAF mutation V600E

Cancer types: Cutaneous melanoma and colorectal cancer
Tissue analyzed: Tumor
How used: To predict response to targeted therapies

CA15-3/CA27.29

Cancer type: Breast cancer
Tissue analyzed: Blood
How used: To assess whether treatment is working or disease has recurred

CA19-9

Cancer types: Pancreatic cancer, gallbladder cancer, bile duct cancer, and gastric cancer
Tissue analyzed: Blood
How used: To assess whether treatment is working

CA-125

Cancer type: Ovarian cancer
Tissue analyzed: Blood
How used: To help in diagnosis, assessment of response to treatment, and evaluation of recurrence

Calcitonin

Cancer type: Medullary thyroid cancer
Tissue analyzed: Blood
How used: To aid in diagnosis, check whether treatment is working, and assess recurrence

Carcinoembryonic antigen (CEA)

Cancer types: Colorectal cancer and breast cancer
Tissue analyzed: Blood
How used: To check whether colorectal cancer has spread; to look for breast cancer recurrence and assess response to treatment

CD20

Cancer type: Non-Hodgkin lymphoma
Tissue analyzed: Blood
How used: To determine whether treatment with a targeted therapy is appropriate

Chromogranin A (CgA)

Cancer type: Neuroendocrine tumors
Tissue analyzed: Blood
How used: To help in diagnosis, assessment of treatment response, and evaluation of recurrence

Chromosomes 3, 7, 17, and 9p21

Cancer type: Bladder cancer
Tissue analyzed: Urine
How used: To help in monitoring for tumor recurrence

Cytokeratin fragments 21-1

Cancer type: Lung cancer
Tissue analyzed: Blood
How used: To help in monitoring for recurrence

EGFR mutation analysis

Cancer type: Non-small cell lung cancer
Tissue analyzed: Tumor
How used: To help determine treatment and prognosis

Estrogen receptor (ER)/progesterone receptor (PR)

Cancer type: Breast cancer
Tissue analyzed: Tumor
How used: To determine whether treatment with hormonal therapy (such as tamoxifen) is appropriate

Fibrin/fibrinogen

Cancer type: Bladder cancer
Tissue analyzed: Urine
How used: To monitor progression and response to treatment

HE4

Cancer type: Ovarian cancer
Tissue analyzed: Blood
How used: To assess disease progression and monitor for recurrence

HER2/neu

Cancer types: Breast cancer, gastric cancer, and esophageal cancer
Tissue analyzed: Tumor
How used: To determine whether treatment with trastuzumab is appropriate

Immunoglobulins

Cancer types: Multiple myeloma and Waldenström macroglobulinemia
Tissue analyzed: Blood and urine
How used: To help diagnose disease, assess response to treatment, and look for recurrence

KIT

Cancer types: Gastrointestinal stromal tumor and mucosal melanoma
Tissue analyzed: Tumor
How used: To help in diagnosing and determining treatment

KRAS mutation analysis

Cancer types: Colorectal cancer and non-small cell lung cancer
Tissue analyzed: Tumor
How used: To determine whether treatment with a particular type of targeted therapy is appropriate

Lactate dehydrogenase

Cancer type: Germ cell tumors
Tissue analyzed: Blood
How used: To assess stage, prognosis, and response to treatment

Nuclear matrix protein 22

Cancer type: Bladder cancer
Tissue analyzed: Urine
How used: To monitor response to treatment

Prostate-specific antigen (PSA)

Cancer type: Prostate cancer
Tissue analyzed: Blood
How used: To help in diagnosis, assess response to treatment, and look for recurrence

Thyroglobulin

Cancer type: Thyroid cancer
Tissue analyzed: Tumor
How used: To evaluate response to treatment and look for recurrence

Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1)

Cancer type: Breast cancer
Tissue analyzed: Tumor
How used: To determine aggressiveness of cancer and guide treatment

5-Protein signature (Ova1)

Cancer type: Ovarian cancer
Tissue analyzed: Blood
How used: To pre-operatively assess pelvic mass for suspected ovarian cancer

21-Gene signature (Oncotype DX)

Cancer type: Breast cancer
Tissue analyzed: Tumor
How used: To evaluate risk of recurrence

70-Gene signature (Mammaprint)

Cancer type: Breast cancer
Tissue analyzed: Tumor
How used: To evaluate risk of recurrence

Reference:www.cancer.gov