GRADING & STAGING TUMOUR MARKERS

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• Prognosis of the course of the disease

• Determination of efficacy of various forms of cancer treatment require a high degree of similarity among the tumors being considered.

• Systems in semiquantitative terms,

• The level of differentiation, or grade• Extent of spread of a cancer within the patient,

or stage,

Grading of a cancer is based

• Degree of differentiation of the tumor cells and the number of mitoses within the tumor as presumed correlates of the neoplasm's aggressiveness.

• Grades I to IV with increasing anaplasia.

• Criteria for the individual grades vary with each form of neoplasia,

• To judge the extent to which the tumor cells resemble or fail to resemble their normal counterparts.

• The correlation between histologic appearance and biologic behavior is less than perfect.

• Characterize a particular neoplasm in descriptive terms,

• Well-differentiated, mucin-secreting adenocarcinoma of the stomach, or

• Highly undifferentiated, retroperitoneal malignant tumor-probably sarcoma.

Cytologic grading of squamous cell carcinoma of the lung.

A. Well-differentiated (grade 1) squamous cell carcinoma

Poorly differentiated (grade 3) squamous cell carcinoma. The malignant cells are difficult to identify

as being of squamous origin.

• Grading of cancers has proved of less clinical value than has staging

The staging of cancers

• Based on the size of the primary lesion, • Its extent of spread to regional lymph nodes, • Presence or absence of blood-borne

metastases

• Great importance in the selection of the best form of therapy

• Staging has proved to be of greater clinical value than grading

• Union Internationale Contre Cancer (UICC)

• American Joint Committee (AJC) on Cancer Staging.

The UICC employs a classification called the TNM system-

• T for primary tumor, • N for regional lymph node involvement • M for metastases.

The TNM staging varies for each specific form of cancer, but there are general principles

• With increasing size, the primary lesion is characterized as T1 to T4.

• T0 is added to indicate an in situ lesion. .

• N0 would mean no nodal involvement,

whereas N1 to N3 would denote involvement of an increasing number and range of nodes

• M0 no distant metastases, • M1 or sometimes M2

AJC divides all cancers into stages 0 to IV

• Incorporating within each of these stages the size of the primary lesion , presence of nodal spread & distant metastases.

• Stage 0. DCIS or LCIS (5-year survival rate: 92%).

• Stage I.

Invasive carcinoma 2 cm or less in diameter (including carcinoma in situ with microinvasion) without nodal involvement (5-year survival rate: 87%).

Stage II• Invasive carcinoma 5 cm or less in diameter

with up to three involved axillary nodes or

• Invasive carcinoma greater than 5 cm without nodal involvement (5-year survival rate: 75%).

Stage III

• Invasive carcinoma 5 cm or less in diameter with four or more involved axillary nodes;

• Invasive carcinoma greater than 5 cm in diameter with nodal involvement;

• Invasive carcinoma with 10 or more involved axillary nodes;

• Invasive carcinoma with involvement of the ipsilateral internal mammary lymph nodes; or

• Invasive carcinoma with skin involvement (edema, ulceration, or satellite skin nodules), chest wall fixation, or clinical inflammatory carcinoma (5-year survival rate: 46%).

• Stage IV. Any breast cancer with distant metastases (5-year survival rate: 13%).

Tumor Markers

Tumor MarkersBiochemical indicators of the presence of a tumor.

• A molecule that can be detected in plasma or other body fluids

• Tumor markers cannot be primary diagnosic modalities

• Utility to support the diagnosis. • Response to therapy • Indicating relapse during the

follow-up period.

•Cell-surface antigens, •Cytoplasmic proteins, •Enzymes, •Hormones.

CEA A complex glycoprotein

Elevations in many benign disorders

• Alcoholic cirrhosis, • Hepatitis, • Ulcerative colitis, • Crohn disease

•60% to 90% of colorectal, •50% to 80% of pancreatic•25% to 50% of gastric and breast carcinomas

Normally produced in embryonic tissue of the gut, pancreas, and liver

Lack both specificity and the sensitivity required for the detection of early cancers

• Preoperative CEA levels body burden of tumor.• Elevated CEA levels 6 weeks after therapy indicates

residual disease.• A rising CEA level indicates recurrence, with an

increase in tumor marker level often preceding clinically detectable disease.

• Serum CEA is also useful in monitoring the treatment of metastatic breast cancer.

AFP Glycoprotein

• Useful indicator of hepatocellular carcinomas and germ cell tumors of the testis.

• Decline rapidly after surgical resection of liver cell cancer or treatment of germ cell tumors.

• Less regularly in carcinomas of the colon, lung, and pancreas

Early in Fetal Life,Yolk Sac, Fetal Liver & Fetal Git

Adults with cancer arising principally inLiver Germ cells of the testis.

Markers Associated CancersHormonesHuman chorionic gonadotropin

Trophoblastic tumors, nonseminomatous testicular tumors

Calcitonin Medullary carcinoma of thyroid

Catecholamine PheochromocytomaEctopic hormones Paraneoplastic Syndromes

Oncofetal Antigensα-Fetoprotein Liver cell cancer,

nonseminomatous germ cell tumors of testis

Carcinoembryonic antigen

Carcinomas of the colon, pancreas, lung, stomach,

IsoenzymesProstatic acid phosphatase

Prostate cancer

Neuron-specific enolase Small cell cancer of lung, neuroblastoma

Specific ProteinsImmunoglobulins Multiple myeloma and other

gammopathiesProstate-specific antigen and prostate-specific membrane antigen

Prostate cancer

Mucins and Other GlycoproteinsCA-125 Ovarian cancerCA-19-9 Colon cancer, pancreatic cancerCA-15-3 Breast cancer

New Molecular Markersp53, APC, RAS mutations in stool and serum

Colon cancer

p53 and RAS mutations in stool and serum

Pancreatic cancer

p53 and RAS mutations in sputum and serum

Lung cancer

p53 mutations in urine Bladder cancer

Serologic Diagnosis

• Theoretically, it may be possible to diagnose cancer by detecting cancer cell products in the serum, whether these are molecules secreted by malignant cells or antigens released by periodic death of such cells.

• No general serologic screening methods exist for cancer, but several tests are of value for certain tumors

Radiologic Diagnosis

• CT & (MRI) scans, are invaluable for localizing masses as part of the primary diagnosis or for staging tumors.

• As a general rule, radiologic findings suggestive of cancer must be confirmed by either cytologic or histologic examination of biopsy material before treatment can be started.